EP4702000A1 - Alkylation process - Google Patents

Abstract

A process comprises reacting a carbonyl compound with an alkene compound in the presence of an iridium catalyst, wherein the carbonyl compound comprises a nitrogen-based group in a position that is α or β to the carbonyl group and wherein the process comprises the step of α- alkylation of the carbonyl compound by carbon-carbon bond formation between the carbon atom α to the carbonyl group and a carbon atom of the double bond of the alkene compound. The process allows the preparation of amino acid derivatives and other compounds. The process has the flexibility to yield compounds with a range of substituents, with good levels of step and atom economy and selectivity.

Description

ALKYLATION PROCESS The present invention relates to the field of organic chemistry synthesis, and more specifically to the metal-catalysed alkylation of carbonyl compounds. The present invention allows the preparation of amino acid derivatives and other compounds. Amino acids are of extreme synthetic importance, underpinning substantial aspects of biological chemistry, as well as functioning as important building blocks for small molecule targets or chiral materials. One way of accessing amino acids is via the hydrogenation of dehydroamino esters, and perhaps the most well-known commercial application of this technique is the production of L-DOPA as disclosed in W. S. Knowles, J. Chem. Ed.1986, 63, 222-225. However, hydrogenation is challenging to perform across a range of compounds. In particular, tetrasubstituted alkenes are difficult to access and difficult to hydrogenate. The present invention addresses a need to provide a process which has the flexibility to yield compounds with a range of substituents, with good levels of step and atom economy and selectivity. From a first aspect the present invention provides a process comprising reacting a carbonyl compound with an alkene compound in the presence of an iridium catalyst, wherein the carbonyl compound comprises a nitrogen-based group in a position that is α or β to the carbonyl group and wherein the process comprises the step of α-alkylation of the carbonyl compound by carbon-carbon bond formation between the carbon atom α to the carbonyl group and a carbon atom of the double bond of the alkene compound. We have found that the above-mentioned nitrogen-based group, α or β to the carbonyl group, can be effective in promoting the reaction, in combination with an iridium catalyst. The nitrogen atom of the nitrogen-based group is bonded to either the carbon atom in the α position or the carbon atom in the β position. The nitrogen-based group may act as an effective ligating group. The products are amino acid derivatives, by virtue of the presence of the nitrogen-based group and the carbonyl group. The term “amino acid derivative” in general denotes a compound which has: (i) an amino moiety or a moiety which can be considered to be derived from (e.g. is structurally related to) an amino moiety (including a primary, secondary or tertiary amine); and (ii) an acid moiety (i.e. carboxylic acid moiety) or a moiety which can be considered to be derived from (e.g. is structurally related to) an acid moiety (including a moiety containing a carbonyl group, for example a ketone or an amide). Naturally occurring α-amino acids and amino acid derivatives contain a nitrogen-based group and a carbonyl group attached to the same carbon atom. This architecture is achieved in the present invention when the nitrogen-based group is α to the carbonyl group. Also possible in accordance with the present invention is architecture in which the nitrogen-based group is β to the carbonyl group, in which case two carbon atoms, rather than one carbon atom, separate the nitrogen-based group and the carbonyl group. α-Alkylation between the carbonyl group and the nitrogen-based group results in a side chain corresponding to the location of side chains in naturally occurring amino acids. Typically, α- alkylation occurs in this manner in the present invention. This contrasts with alkylation on the other side of the carbonyl group, at what may be termed the α’-position. The nitrogen-based group may optionally be a directing group. The nitrogen-based group may control the selectivity of the reaction. For aliphatic ketone-based systems, the nitrogen- based group enforces α-alkylation and prevents possible alkylation on the other side of the carbonyl group, at what may be termed the α’-position. The nitrogen-based group may exert control over the diastereoselectivity of the reaction. Optionally, the iridium catalyst may be a chiral iridium catalyst, which may be non-racemic or enantiomerically enriched or substantially enantiomerically pure thereby allowing asymmetric catalysis. The process of the present invention is broadly applicable to a range of carbonyl compounds and a range of alkene compounds. Optional substituents herein include substituents which are compatible with the alkylation reaction conditions and do not adversely interact with those conditions. Not only is the method of the present invention surprisingly effective and versatile, but also it was far from predictable that such method would work in practice. The method is a convergent approach in which a new C-C bond and (usually) two stereocentres are established in a single operation. This is a catalytic method that allows the direct α-alkylation of carbonyl compounds. For systems that lack additional strong acidifying groups, this area has proven to be exceptionally Surprisingly, the combination of features of the process of the present invention result in effective alkylation. Without wishing to be bound by theory, it may be that the nitrogen-based group triggers metal-catalyzed “soft” enolization, even with less acidic systems, en route to an enolate. The iridium catalyst may activate both a relatively non-acidic pronucleophile and a non-polarized proelectrophile. This: (a) enables access to β-substituted α-amino acids; (b) offers a unique directing-group-based approach to the direct stereocontrolled α-alkylation of carbonyl compounds; and (c) provides a broader framework for the by-product free installation of contiguous tertiary stereocentres. When a chiral catalyst is used this enables enantio- and diastereoselective reaction. One suitable group of carbonyl compounds include those in which the carbonyl group is part of an amide, for example a primary, secondary or tertiary amide. For example, we have found that the present invention works particularly well with tertiary amides, and several examples of these are presented herein. The amide may optionally be substituted. Where the amide is a tertiary amide, the two groups on the nitrogen atom may either be separate groups or may together form a ring, for example a pyrrolidine, piperidine or morpholine ring. Another suitable group of carbonyl compounds include ketones, in which an aliphatic or aromatic (which may include heteroaromatic) group is attached to the carbonyl group on the other side of the ketone relative to the side which carries the nitrogen-based group. The aliphatic group may include saturated or unsaturated, linear or branched, substituted or unsubstituted, alkyl chains, optionally with between 1 and 20 carbon atoms, optionally between 1 and 10 carbon atoms, optionally between 1 and 5 carbon atoms. The aromatic group may include substituted or unsubstituted aromatic or heteroaromatic groups, optionally with up to 20 carbon atoms, optionally up to 10 carbon atoms, for example a substituted or unsubstituted phenyl group. The carbon atom to which the nitrogen-based group is attached (i.e. the alpha carbon or the beta carbon) may be otherwise unsubstituted (i.e. may carry two hydrogen atoms) or may carry one other substituent and a hydrogen atom. One suitable type of nitrogen-based group include amines, for example secondary amines, for example secondary aromatic amines. These may have the structure -NHAr wherein Ar may be an aromatic group (e.g. phenyl) which may optionally be substituted. The alkene compound comprises a carbon-carbon double bond which may optionally be mono-, di-, tri- or tetrasubstituted or which is unsubstituted, i.e. each carbon atom of the double bond may carry up to two moieties. The invention is most applicable to an alkene compound which comprises a carbon-carbon double bond which is mono-, di- or trisubstituted or unsubstituted, particularly an alkene compound which comprises a carbon-carbon double bond which is mono- or disubstituted or unsubstituted. One suitable group of alkene compounds comprises alkene compounds which are monosubstituted, i.e. in which one carbon atom of the double bond carries a moiety and a hydrogen atom, and the other carbon atom of the double bond carries two hydrogen atoms: in such cases we have generally observed regioselectivity in favour of branched products rather than linear products, i.e. carbon-carbon formation to the substituted carbon atom of the double bond. Further substitution arrangements are possible: for example, another suitable group of alkene compounds comprises alkene compounds in which one carbon atom of the double bond is disubstituted, and in which the other carbon atom of the double bond carries two hydrogen atoms (i.e. 1,1-disubstituted alkenes); and another suitable group of alkene compounds comprises alkene compounds in which one carbon atom of the double bond is monosubstituted, and in which the other carbon atom of the double bond is also monosubstituted (i.e.1,2-disubstituted alkenes). It will be understood that the chemical structure of the moieties carried by the alkene compound is not particularly limited so long as said moieties are compatible with the alkylation reaction conditions. Indeed, one advantage of the present invention is that it allows a broad range of side chains, including those of complex structure, to be introduced to amino acid derivatives. One possible process in accordance with the present invention is a process which comprises reacting the compound of formula I with formula II in the presence of an iridium catalyst and a chiral (e.g. non-racemic, e.g. enantiomerically enriched) phosphine ligand to form the compound of formula III: wherein: n is 0 or 1; and each of R¹ to R¹⁰ is, independently, any group. A “suitable group” is any group which is compatible with the reaction of the compound of formula I with the compound of formula II to form the compound of formula III. This is an alkylation reaction wherein a bond forms between the alpha carbon atom of the compound of formula I and one of the carbon atoms of the double bond of the compound of formula II, and a synthetic organic chemist is aware, or is easily able to determine, which groups are suitable in each of the R¹ to R¹⁰ positions. Typically, each of R¹ to R¹⁰ in the starting materials (i.e. in I and II) maintains its identity in the product (i.e. in III). Nevertheless, it is possible that in certain cases one or more of R¹ to R¹⁰ may change its identity in the product, so long as the alkylation process still occurs. Optionally R¹ may be NR¹¹R¹² wherein R¹¹ and R¹² are independently selected from: saturated or unsaturated, linear or branched, unsubstituted or substituted alkyl or heteroalkyl; unsubstituted or substituted aryl or heteroaryl; or H; or R¹¹ and R¹² may together form a ring. Optionally, it may be that primary amides are excluded from the definition of the invention in this position, namely that a proviso may apply, that R¹¹ and R¹² may not both be H. Optionally R¹ may be selected: from saturated or unsaturated, linear or branched, unsubstituted or substituted alkyl or heteroalkyl; unsubstituted or substituted aryl or heteroaryl. Each “alkyl” or “heteroalkyl” group may optionally have between 1 and 20 carbon atoms, or between 1 and 10 carbon atoms, or between 1 and 5 carbon atoms, or between 1 and 4 carbon atoms, or between 1 and 3 carbon atoms, or 1 or 2 carbon atoms, or 1 carbon atom (i.e. in some cases may be a methyl group). Each “aryl” or “heteroaryl” group may comprise a single ring or fused rings, with or without heteroatoms, and optionally may have up to 20 carbon atoms, or up to 10 carbon atoms, or up to 6 carbon atoms, for example in some cases may be a phenyl group. Possible types of “aryl” include metallocene. Where R¹ is NR¹¹R¹², and where R¹¹ and R¹² together form a ring, optionally the NR¹¹R¹² unit may (including the nitrogen atom) be a 3-membered, 4-membered, 5-membered, 6- membered, 7-membered or 8-membered ring, or may comprise such ring, optionally fused or bonded to one or more other ring(s). The term “substituted” denotes that any suitable substituent may be present. Thus, for example, alkyl or heteroalkyl groups may be substituted by virtue of carrying aryl or heteroaryl groups, or vice-versa. The term “substituted” also denotes that linking groups (e.g. esters, ethers, and amides) may be present and that a plurality of moieties may be present in a substituent. Non-limiting examples of possible substituents and linking groups include alkyl, heteroalkyl, aryl, heteroaryl, halides, ethers, esters, and amides. R¹ may for example be N(CH3)2, NHCH3, N(CH2CH3)2, NHPh, pyrrolidine, piperidine, morpholine, CH₃, tertiary butyl or phenyl. Optionally R² may be: unsubstituted or substituted aryl or heteroaryl; saturated or unsaturated, linear or branched, unsubstituted or substituted alkyl or heteroalkyl; or H. In R², an “aryl” or “heteroaryl” group may comprise a single ring or fused rings, with or without heteroatoms, and optionally may have up to 20 carbon atoms, or up to 10 carbon atoms, or up to 6 carbon atoms, for example in some cases may be a phenyl group. R² may be or may comprise a metallocene moiety. An “alkyl” or “heteroalkyl” group may optionally have between 1 and 20 carbon atoms, or between 1 and 10 carbon atoms, or between 1 and 5 carbon atoms, or between 1 and 4 carbon atoms, or between 1 and 3 carbon atoms, or 1 or 2 carbon atoms, or 1 carbon atom (i.e. in some cases may be a methyl group). The term “substituted” denotes that any suitable substituent may be present. Thus, for example, alkyl or heteroalkyl groups may be substituted by virtue of carrying aryl or heteroaryl groups, or vice-versa. The term “substituted” also denotes that linking groups (e.g. esters, ethers, and amides) may be present and that a plurality of moieties may be present in a substituent. Non- limiting examples of possible substituents and linking groups include alkyl, heteroalkyl, aryl, heteroaryl, halides, ethers, esters and amides. R² may for example be an aromatic or heteroaromatic moiety (for example a phenyl group), which may optionally carry further substituent(s). Optionally R³ may be: unsubstituted or substituted aryl or heteroaryl; or saturated or unsaturated, linear or branched, unsubstituted or substituted alkyl or heteroalkyl. In R³, an “aryl” or “heteroaryl” group may comprise a single ring or fused rings, with or without heteroatoms, and optionally may have up to 20 carbon atoms, or up to 10 carbon atoms, or up to 6 carbon atoms, for example in some cases may be a phenyl group. R³ may be or may comprise a metallocene moiety. An “alkyl” or “heteroalkyl” group may optionally have between 1 and 20 carbon atoms, or between 1 and 10 carbon atoms, or between 1 and 5 carbon atoms, or between 1 and 4 carbon atoms, or between 1 and 3 carbon atoms, or 1 or 2 carbon atoms, or 1 carbon atom (i.e. in some cases may be a methyl group). The term “substituted” denotes that any suitable substituent may be present. Thus, for example, alkyl or heteroalkyl groups may be substituted by virtue of carrying aryl or heteroaryl groups, or vice-versa. The term “substituted” also denotes that linking groups (e.g. esters, ethers, and amides) may be present and that a plurality of moieties may be present in a substituent. Non- limiting examples of possible substituents and linking groups include alkyl, heteroalkyl, aryl, heteroaryl, halides, ethers, esters and amides. R⁴ may be independently selected from the groups specified herein for R³ or may be H. R³ and R⁴ may together form a ring. An important sub-set of the invention is that in which R⁴ is H. R³ may for example be phenyl or substituted phenyl. R⁴ may for example be H. When R³ is substituted phenyl, possible non-limiting examples of said substituents include hydroxy, methoxy, methyl, fluoro, chloro, trifluoromethyl, or two or more of these. One of said substituents can be for example in the para position. Each of R⁵, R⁹ and R¹⁰ may each optionally be independently selected from the groups specified herein for R². R⁵ may for example be H or methyl. R⁹ and R¹⁰ may for example be H. Optionally R⁶, R⁷ and R⁸ may each independently be selected from: saturated or unsaturated, linear or branched, unsubstituted or substituted alkyl or heteroalkyl; unsubstituted or substituted aryl or heteroaryl; or H. Each “alkyl” or “heteroalkyl” group may optionally have between 1 and 20 carbon atoms, or between 1 and 10 carbon atoms, or between 1 and 5 carbon atoms, or between 1 and 4 carbon atoms, or between 1 and 3 carbon atoms, or 1 or 2 carbon atoms, or 1 carbon atom (i.e. in some cases may be a methyl group). Each “aryl” or “heteroaryl” group may comprise a single ring or fused rings, with or without heteroatoms, and optionally may have up to 20 carbon atoms, or up to 10 carbon atoms, or up to 6 carbon atoms, for example in some cases may be a phenyl group. Possible types of “aryl” include metallocene. It may be that R⁶, R⁷ and R⁸ are each H. The above definitions of possible moieties, groups and substituents represent merely some possibilities. Alternatively, or additionally, other moieties, groups or substituents may be used so long as these are compatible with the reaction of the compound of formula I with the compound of formula II to form the compound of formula III. For example, other possibilities for R² include boron-containing groups, including boronic acids or esters, or boronates. These may optionally comprise or be linked to alkyl or heteroalkyl groups as defined above, may optionally comprise or be linked to aryl or heteraryl groups, may be saturated or contain unsaturation, and/or may be unsubstituted or substituted, as defined above, including the possibility that linking groups may optionally be present and that a plurality of moieties may optionally be present in a substituent. One example of a boron-containing group is pinacolatoboron (“BPin”). Therefore, optionally R² may be: unsubstituted or substituted aryl or heteroaryl; saturated or unsaturated, linear or branched, unsubstituted or substituted alkyl or heteroalkyl; H; or a boron-containing group. Each of R⁵, R⁹ and R¹⁰ may each optionally be independently selected from the groups specified herein for R². R⁵ may for example be H or methyl. R⁹ and R¹⁰ may for example be H. It may be that the alkene compound is substituted on only one of the two carbon atoms of the double bond, namely that R⁹ and R¹⁰ are both H. In this scenario the structural formulae may be as follows: The above representation of formula III assumes that a bond is formed from the alpha carbon atom of the carbonyl compound to the more substituted carbon atom of the double bond, thereby forming a branched compound with a methyl group and R² and R⁵ groups being carried by said carbon atom in product III. Alternatively, reaction may occur by bond formation to the CH2 group of the double bond in some cases to yield a less branched chain (or a linear chain if one of R² and R⁵ is H). We have found that in general the reaction exhibits selectivity in favour of the more branched product as drawn above, rather than the less branched or linear isomer. It may be that n is 0, in which case the structural formulae are as follows. In this scenario, the nitrogen-based group is on the alpha carbon. It may be that both n is zero, and the alkene compound is substituted on only one of the two carbon atoms of the double bond, namely that R⁹ and R¹⁰ are both H. In this scenario the structural formulae may be as follows: It may be that the nitrogen-based group is a secondary amine, i.e. R⁴ may be H. It may be that the alkene compound has only one substituent, i.e. not only R⁹ and R¹⁰, but also R⁵, may be H. It may be that the carbonyl compound is not substituted at the alpha position other than with the nitrogen-based group, i.e. R⁶ may be H. These possibilities may be combined, so for example the process may proceed according to the following structural formulae:

One of the advantages of the present invention is that it provides access to molecules which are otherwise difficult to synthesise. The present invention allows the preparation of many types of amino acid derivatives, because the coupling step tolerates a broad range of chemical structures and functional groups in the starting materials (I and II). Either or both of the starting materials (I and II) may have a complex structure if desired. In particular, it should be noted that the alkylation coupling step adds an amino acid side chain and therefore the present invention allows this to be tailored simply by choosing an appropriate alkene compound II. The process of alkylation at the alpha carbon atom of the carbonyl compound forms a chiral centre at that carbon atom. The process may be regioselective in favour of forming a bond to the carbon atom of the double bond of the alkene compound which carries the R² substituent. Where R⁵, R⁹ and R¹⁰ are H, this results in a branched structure, referred to herein as “B”. The alternative product is a linear product, referred to herein as “L”. The ratio of B to L formed in the reaction (“B:L”) may optionally be >10:1 or >20:1 or >30:1. Where R⁵, R⁹ and R¹⁰ are H, the branched product contains a chiral centre at the carbon atom carrying the R² substituent, but the linear product does not have a chiral centre at that location. Therefore, when the reaction product is the branched product, two adjacent chiral centres are formed. The iridium catalyst may optionally be a chiral iridium catalyst. This can result in a degree of regioselectivity, enantioselectivity and/or diastereoselectivity. We have observed branch selectivity combined with enantioselectivity and diastereoselectivity. Optionally the reaction may be diastereoselective, resulting in a diastereomeric ratio of 2:1 or greater, or 3:1 or greater, or 4:1 or greater, or 5:1 or greater, or 6:1 or greater, or 7:1 or greater, or 8:1 or greater, or 9:1 or greater, or 10:1 or greater, or 15:1 or greater, or 20:1 or greater. Optionally the reaction may be enantioselective, resulting in an enantiomeric ratio of 70:30 or greater, or 75:25 or greater, or 80:20 or greater, or 85:15 or greater, or 90:10 or greater, or 95:5 or greater, or 96:4 or greater, or 97:3 or greater, or 98:2 or greater. Without wishing to be bound by theory, it is postulated that the nitrogen-based directing group (of the carbonyl compound) and chiral Iridium catalyst facilitate enolization via initial NH metalation, and that the resulting stereodefined enolate engages an alkene in a selective orientation. Without wishing to be bound by theory, it is possible that the process proceeds via a sequence of alkene carbometallation and C-H reductive elimination. Compound I is particularly well configured for enolate formation with the chiral Ir catalyst that is formed. Without wishing to be bound by theory, it is believed that the adjacent directing group ligates to the chiral Ir-based system. Coordination of the carbonyl unit in compound I then facilitates enolization in advance of a bond-forming event. The cyclic nature of the enolate chelate automatically controls enolate geometry, which, in turn, may control selectivity, and the presence of the redox active Ir centre offers many possibilities with respect to the reaction partner compound II and therefore the C-C bond forming step. The large number of possible identities of the R¹ to R¹⁰ groups provide access to a range of compounds and most importantly to complex products which are otherwise difficult to obtain through standard procedures known in the art. If asymmetric reaction is desired, the iridium catalyst is suitably an iridium species with a chiral ligand, which is non-racemic or enantio-enriched. This may be prepared in situ from an iridium compound and a chiral ligand. The iridium compound may comprise cyclooctadiene (cod) ligands or other ligands, e.g. 2 cod ligands, coordinated to the iridium centre. The iridium species may be an iridium (I) species. A range of counterions may be used with cationic iridium (I): these counterions include for example tetrakis[3,5- bis(trifluoromethyl)phenyl]borate (BARF), tetrafluoroborate (BF⁴), triflate (OTf), chloride (Cl) or methoxide (OMe) amongst others. Examples of suitable iridium compounds are: Ir(cod)₂BARF; Ir(cod)₂BF₄; Ir(cod)₂OTf; [Ir(cod)Cl]₂; and [Ir(cod)OMe]₂. The iridium catalyst may be an iridium source which may be combined with a chiral or achiral ligand in situ or ex situ to form a suitable iridium species. Suitable ligands include phosphine (e.g. diphosphine) ligands. Phosphine modified iridium systems (e.g. diphosphine modified cationic iridium (I) systems) are Lewis acidic and this is advantageous in promoting the reaction. Other Lewis acidic systems may be used. The iridium species may be bound to a chiral ligand which is a phosphine ligand. The phosphine ligand may be a diphosphine ligand. The chiral ligand may displace other ligands on the iridium centre. Some examples of suitable chiral phosphine ligands are: (R)-BINAP; (R)-tol-BINAP; (R)-DM-BINAP; (R)-H8-BINAP; (R)-SEGPHOS; (R)-DM-SEGPHOS; (R)- DTBM-SEGPHOS; (R)-MeOBIPHEP; and (R)-SDP. Other chiral phosphine ligands may be used. The chiral phosphine ligand may be monodentate or bidentate.

The reagents and catalytic system are compatible with a range of solvents. Some solvents which have been used include: toluene; 1,4-dioxane; THF; PhCl; PhCF3; t-BuOH; or 1,2-DCP. Some possible reaction conditions will now be described. The process may be carried out under inert gas conditions, for example under nitrogen or argon. Apparatus suitable for this purpose include a Schlenk tube or other apparatus which allow a vessel to be evacuated or filled with inert gas. Optionally the gaseous environment in the reaction vessel may be at least 99%, or at least 99.5% or at least 99.9% inert gas by volume. The process may be carried out under anhydrous conditions, using anhydrous solvent(s). Optionally there may be less than 1% or less than 0.5% or less than 0.1% or less than 0.01% water present by volume in the solvent. The amount of solvent used may vary. The molarity with respect to the carbonyl compound (compound I) may be 0.01-10M, or 0.05-5M, or 0.1-2M, or 0.1-1M or approximately 0.5M. The relative molar amounts of carbonyl compound (I) and alkene compound (II) used as reagents may vary. Optionally, 1-10 equivalents, or 1-6 equivalents, or 1.5-6 equivalents, or 1.5-3 equivalents, or 1.5-2.5 equivalents, or about 2 equivalents, of alkene compound (II) are used relative to carbonyl compound (I). The reaction may be carried out at an appropriate temperature and for an appropriate time for suitable conversion to occur. Optionally the reaction temperature may be room temperature (e.g. about 20 to 25 degrees C), or higher, e.g. room temperature (e.g. about 20 to 25 degrees C) to 300 degrees C, or within the range of 30-300, or 40-300, or 50-300, or 60-300, or 70-300, or 80-250, or 80-200, or 100-200, or 100-150, or 105-140, or 110-130, or about 130, degrees C. Optionally the reaction time may be 3 hours to 4 days, or 12 hours to 4 days, or 1 to 4 days, or 2 to 4 days, or about 3 days. Suitable amounts of iridium catalyst may be used. These include for example 0.01-10 mol%, or 0.05-10 mol%, or 0.1-10 mol%, or 0.1-8 mol%, or 1-7 mol%, or 1-6 mol% or 2-6 mol%, or 3-6 mol%, or 4-6 mol% or about 5 mol%. A corresponding amount of chiral ligand may be used, for example 0.1-10 mol%, or 0.1-8 mol%, or 1-7 mol%, or 1-6 mol% or 2-6 mol%, or 3- 6 mol%, or 4-6 mol% or about 5 mol%. The process may comprise: charging a vessel (e.g. under inert gas conditions) with the carbonyl compound, iridium compound and chiral ligand, followed by charging the vessel (e.g. under inert gas conditions) with the alkene compound and (e.g. anhydrous) solvent, and allowing the reaction to proceed (e.g. under inert gas conditions), optionally at elevated temperature, for the desired period of time. Alternate orders of addition can be used as is convenient based on the physical properties of the reagents and the experimental setup. The product may then be isolated and purified (e.g. under air) by conventional techniques, for example allowing the reaction mixture to cool to room temperature, removal of solvent under reduced pressure, and use of chromatographic or crystallisation techniques. From further aspects the present invention provides products as described herein including compounds which are products of the process of the present invention and compounds prepared by derivatisation steps. Figures Non-limiting examples in accordance with the present invention will now be described in further detail with reference to the following Figures in which: Figure 1 shows a reaction scheme according to certain embodiments of the present invention, and a comparative theoretical alternative process; Figures 2 and 3 shows some compounds which have been synthesized by using the process of the present invention; and Figures 4 and 5 show some examples of applications and derivatizations facilitated by the present invention. General experimental details All reagents requiring purification were purified using standard laboratory techniques according to methods published by Armarego, and Perrin (Pergamon Press, 1966). Catalytic reactions were carried out in Young-type re-sealable tubes. Styrene and other commercially available alkenes (liquid) were quickly distilled using a Hickman distilling head before use. All other commercially available alkenes (solid) were used as received without any further purification. Iridium catalysts were synthesized according to previously reported procedures^1,2. Anhydrous THF, toluene, and CH2Cl2 were obtained by either passed through drying columns supplied by Anhydrous Engineering Ltd or purchased from commercial sources (Acros or Aldrich). Anhydrous 1,4-dioxane, DMF, DMA, DMSO and CH3CN were purchased as anhydrous grade and stored over activated 4Å molecular sieves prior to use. All reactions were performed using dry solvents unless stated otherwise. Triethylamine (TEA) was distilled over CaH₂ and stored over activated 4Å molecular sieves under nitrogen. Flash column chromatography (FCC) was performed using silica gel (Aldrich 40-63 µm, 230-400 mesh). Thin layer chromatography was performed using aluminium backed 60 F254 silica plates. Visualisation was achieved by UV fluorescence or a basic KMnO4 solution and heat. Proton nuclear magnetic resonance spectra (NMR) were recorded at 400 MHz or 500 MHz as stated. ¹³C NMR spectra were recorded at 125 MHz as stated. Chemical shifts (δ) are given in parts per million (ppm). Peaks are described as singlets (s), doublets (d), triplets (t), quartets (q), septets (sept), multiplets (m) and broad (br.). Coupling constants (J) are quoted to the nearest 0.5 Hz. When compounds were isolated as a mixture of diastereoisomers, they are referred to as a (major) and b (minor). In situ yields were determined by employing 1,3,5- trimethoxybenzene as the internal standard. High resolution mass spectra were determined by the University of Liverpool mass spectrometry service, given to four decimal places. Mass spectra were recorded on Agilent 7200 Accurate Mass QTOF GC/MS (under condition of chemical ionization-CI) and Agilent 6540 UHD Accurate Mass Q-TOF LC/MS (under condition of electrospray ionization-ESI). Infrared spectra were recorded on a Perkin Elmer Spectrum Two FTIR spectrometer as thin films or solids compressed on a diamond plate. Melting points were determined using Reichert melting point apparatus and are uncorrected. Optical rotations were measured using an ADP440⁺ polarimeter at the concentration and temperature stated. Enantiomeric excesses were determined using an Agilent 1290 Infinity chiral SFC as stated for each compound. Experimental procedures and data The following table shows results in respect of a first series of reactions, wherein R¹ is NMe2, R² is Ph, R³ is Ph, R⁴ to R¹⁰ are H and n is zero. Iridium catalysts have been found to be surprisingly effective. The row in which the catalyst is a Rhodium catalyst is not an example of the present invention and is provided as a comparative example. The above table shows reasonable to high yields. It should be noted that these are yet to be optimised and it is expected that higher yields are expected to be achieved. The above table furthermore shows that high enantioselectivities and diastereoselectivities can be achieved. Figure 1 shows a reaction scheme, in which for clarity only some functional groups are indicated. The amino acid derivatives (shown in a box in Figure 1) which are accessible by the process of the present invention could theoretically be made by an alternative route, namely hydrogenation of unsaturated compounds (right-hand side of Figure 1), but this is disadvantageous in terms of access to starting materials and process efficacy, and is less compatible with complex structure preparation. Figures 2 and 3 show examples of chemical structures of products of the process of the present invention, together with data regarding yields, enantiomeric ratios, diastereomeric ratios and branched:linear (B:L) ratios. Experimental details for the synthesis and characterization of these products are provided below, but in summary the conditions were as follows: ^b The reaction temperature was 90 ^oC. ^c R-DTBM-SEGPHOS was used as ligand. ^d The reaction temperature was 90 ^oC. ^e The reaction time was 22 h. ^f The reaction temperature was 140 ^oC and amide starting material was recovered in 35% yield. ^g alkene (1000 mol%), R-DM- SEGPHOS (10 mol%) and [Ir(cod)2]BARF (10 mol%) were used at 110 ^oC in mesitylene. ^h styrene (300 mol%), R-BINAP (10 mol%) and [Ir(cod)₂]BARF (10 mol%) were used at 140 ^oC; the minor diastereomer was formed in 71:29 e.r. Figures 2 and 3 show some possible variations of the R¹, R² and R³ groups, and examples of compounds in which n is zero and an example where n is 1. In these Figures, each of R⁵ to R¹⁰ is H. Nevertheless, numerous other variations are possible and within the scope of the present invention despite not being shown in Figures 2 and 3. For example, the alkene compound may be ethylene (i.e. each of R², R⁵, R⁹ and R¹⁰ may be H) or there may be multiple substituents on the alkene compound (e.g. at R² and R⁵). Examples of these are as follows: H O Ir(cod) BARF (5 H O N ₂ mol%) Ph rac-BINAP (5 mol%) N Ph HO 1,4-dioxane (0.5 M) (1 atm.) 100 oC, 4 h ^HO ee h Experimental details are provided below for further compounds including wherein R¹ is morpholino, R² is meta-chloro-phenyl, and R³ is para-hydroxy-phenyl. Some examples of applications and derivatizations in accordance with the present invention are illustrated in Figures 4 and 5. Part A of Figure 4 shows an example of alkylation using an alkene of complex structure derived from indomethacin. Parts B, C and D show some examples (amongst numerous possibilities) of derivatization reactions and how these can provide access to other chemistries. Further details are provided below, but in summary the conditions used herein were as follows: ^a LiAlH₄ (200 mol%), THF, 0 ^oC, 20 min then NaBH₄ (400 mol%), MeOH, 0 ^oC to r.t., 1 h. ^b LiAlH4 (200 mol%), THF, 0 ^oC, 20 min. ^c BH3•THF (500 mol%), THF, 90 ^oC, 4 h. ^d PhLi (200 mol%), THF, 0 ^oC, 15 min. ^e H2SO4/AcOH/H2O (1:3:1), 120 ^oC, 72 h. ^f CAN (150 mol%), MeCH/H2O, 0 ^oC, 1 h. ^g HCl/AcOH, 130 ^oC, 48 h. ^h LiAlH₄ (220 mol%), THF, 70 ^oC, 11 h. ⁱ iodobenzene (120 mol%), NaOH, (200 mol%), CuI (5 mol%), DMSO/H₂O, 90 ^oC, 12 h. CAN = Ce(NH₄)₂(NO₃)₆. Other possible derivatisations include reaction of boron-containing compounds (exemplified in example 25t) in cross-coupling reactions or oxidation to alcohols. Substrate synthesis General procedure A for the synthesis of amides 1a-1o: Amides 1a-1o were synthesized according to a modified procedure.³ An oven- , TEA (0.21 mL, 1.50 mmol, 120 mol%) in anhydrous DMF (5.0 mL) was then added dropwise over 5 minutes at room temperature (r.t.). After the addition was complete, the reaction mixture was stirred for 1-2 hour(s) at r.t. and the progress of the reaction was monitored by TLC. Upon completion, the reaction mixture was transferred to a separatory funnel, and brine (approx. 20.0 mL) was added. The aqueous phase was extracted with EtOAc (approx.3 × 5.0 mL). The combined organic phases were dried over anhydrous MgSO₄, filtered and concentrated in vacuo. The residue was purified by FCC under the conditions noted. N,N-Dimethyl-2-(phenylamino)acetamide (1a): 1 O Me A: Purification by column chromatography (hexane/EtOAc, 50:50) afforded the title compound (116 mg, 65%) as a colorless solid.1H NMR (500 MHz, CDCl₃) δ 7.21 – 7.18 (m, 2H, H⁵), 6.73 – 6.71 (m, 1H, H⁶), 6.63 (d, J = 7.5 Hz, 2H, H⁴), 4.91 (br s, 1H, H³), 3.85 (s, 2H, H²), 3.03 – 3.02 (m, 6H, H¹). The spectroscopic properties were consistent with the data available in the literature.⁴ N-Methyl-2-(phenylamino)acetamide (1b): 1 General procedure A: The reaction mixture was stirred for 19 hours at 70 ^oC using the corresponding α-chloride amide (129 mg, 1.20 mmol, 120 mol%). Purification by column chromatography (hexane/EtOAc, 35:65) afforded the title compound (83.7 mg, 51%) as a pale-yellow solid.1H NMR (500 MHz, CDCl3) δ 7.23 – 7.20 (m, 2H, H⁶), 6.83 – 6.80 (m, 1H, H⁷), 6.75 (br s, 1H, H²), 6.61 (d, J = 8.5 Hz, 2H, H⁵), 4.26 (br s, 1H, H⁴), 3.79 (s, 2H, H³), 2.82 (d, J = 5.0 Hz, 3H, H¹). The spectroscopic properties were consistent with the data available in the literature.⁵ N,N-Diethyl-2-(phenylamino)acetamide (1c): Purification by column chromatography (hexane/EtOAc, 50:50) (144 mg, 70%) as a colorless solid 1 . H NMR (500 MHz, CDCl₃) δ 7.22 – 7.19 (m, 2H, H⁶), 6.76 – 6.73 (m, 1H, H⁷), 6.68 – 6.66 (m, 2H, H⁵), 5.30 (br s, 1H, H⁴), 3.88 (s, 2H, H³), 3.46 (q, J = 7.0 Hz, 2H, H²), 3.32 (q, J = 7.0 Hz, 2H, H^2’), 1.24 (t, J = 7.0 Hz, 3H, H¹), 1.17 (t, J = 7.0 Hz, 3H, H^1’). The spectroscopic properties were consistent with the data available in the literature.⁶ 2-(Phenylamino)-1-(pyrrolidin-1-yl)ethan-1-one (1d): A: Purification by column chromatography (hexane/EtOAc, 65:35) afforded the title compound (120 mg, 59%) as a pale-yellow solid.1H NMR (500 MHz, CDCl₃) δ 7.20 – 7.17 (m, 2H, H⁶), 6.73 – 6.70 (m, 1H, H⁷), 6.63 (d, J = 7.5 Hz, 2H, H⁵), 4.63 (br s, 1H, H⁴), 3.79 (s, 2H, H³), 3.54 (t, J = 7.0 Hz, 2H, H²), 3.41 (t, J = 7.0 Hz, 2H, H^2’), 2.03 – 1.98 (m, 2H, H¹), 1.91 – 1.86 (m, . The spectroscopic 2-(Phenylamino)-1-(piperidin-1-yl)ethan-1-one (1e): General procedure A: Purification by column chromatography (hexane/EtOAc, 65:35) afforded the title compound (80.7 mg, 37%) as a pale-yellow solid.1H NMR (500 MHz, CDCl3) δ 7.21 – 7.17 (m, 2H, H⁷), 6.73 – 6.70 (m, 1H, H⁸), 6.63 (d, J = 7.5 Hz, 2H, H⁶), 4.97 (br s, 1H, H⁵), 3.86 (s, 2H, H⁴), 3.62 (t, J = 5.5 Hz, 2H, H³), 3.37 (t, J = 5.5 Hz, 2H, H^3’), 1.71 – 1.66 (m, 2H, H²), 1.63 – 1.56 (m, 4H, H¹ + H^2’). The spectroscopic properties were consistent with the data available in the literature.⁴ 1-Morpholino-2- A: Purification by column chromatography (hexane/EtOAc, 50:50) (123 mg, 56%) as a pale-yellow solid.1H NMR (500 MHz, CDCl3 ) δ 7.21 – 7.18 (m, 2H, H⁶), 6.75 – 6.72 (m, 1H, H⁷), 6.63 (d, J = 8.0 Hz, 2H, H⁵), 4.82 (br s, 1H, H⁴), 3.86 (s, 2H, H³), 3.71 – 3.67 (m, 6H, H¹ + H²), 3.45 – 3.43 (m, 2H, H^2’). The spectroscopic properties were consistent with the data available in the literature.⁴ 2-((4-Hydroxyphenyl)amino)-N,N-dimethylacetamide (1g): Purification by column chromatography (hexane/EtOAc, 50:50) afforded the title compound (118 mg, 61%) as a pale-yellow solid.1H NMR (500 MHz, CDCl₃) δ 6.72 (d, J = 9.0 Hz, 2H, H⁵), 6.56 (d, J = 9.0 Hz, 2H, H⁴), 4.52 (br s, 1H, H³), 3.83 (s, 2H, H²), 3.03 (s, 6H, H¹). The spectroscopic properties were consistent with the data available in the literature.⁷ 2-((4-Methoxyphenyl)amino)-N,N-dimethylacetamide (1h): General procedure A: Purification by column chromatography (hexane/EtOAc, 50:50) afforded the title compound (146 mg, 70%) as a pale-yellow solid.1H NMR (500 MHz, CDCl3) δ 6.79 (d, J = 9.0 Hz, 2H, H⁵), 6.60 (d, J = 9.0 Hz, 2H, H⁴), 4.58 (br s, 1H, H³), 3.82 (s, 2H, H²), 3.74 (s, 3H, H⁶), 3.01 (s, 6H, H¹). The spectroscopic properties were consistent with the data available in the literature.⁸ N,N-Dimethyl-2-(p-tolylamino)acetamide (1i): Purification by column chromatography (hexane/EtOAc, 50:50) (131 mg, 68%) as a colorless solid.1H NMR (500 MHz, CDCl3) δ , 6.57 (d, J = 8.0 Hz, 2H, H⁴), 4.57 (br s, 1H, H³), 3.84 (s, 2H, H²), 3.02 (s, 6H, H¹), 2.24 (s, 3H, H⁶). The spectroscopic properties were consistent with the data available in the literature.⁹ 2-((4-Fluorophenyl)amino)-N,N-dimethylacetamide (1j): Purification by column chromatography (hexane/EtOAc, 50:50) (141 mg, 72%) as a colorless solid.1H NMR (500 MHz, CDCl₃) δ 6.91 – 6.87 (m, 2H, H⁵), 6.57 – 6.54 (m, 2H, H⁴), 4.72 (br s, 1H, H³), 3.81 (s, 2H, H²), 3.02 (s, 6H, H¹). The spectroscopic properties were consistent with the data available in the literature.⁹ 2-((4-Chlorophenyl)amino)-N,N-dimethylacetamide (1k): General procedure A: Purification by column chromatography (hexane/EtOAc, 50:50) afforded the title compound (160 mg, 75%) as a colorless solid.1H NMR (500 MHz, CDCl3) δ 7.12 (d, J = 8.5 Hz, 2H, H⁵), 6.54 (d, J = 8.5 Hz, 2H, H⁴), 4.90 (br s, 1H, H³), 3.81 (s, 2H, H²), 3.02 (s, 6H, H¹). The spectroscopic properties were consistent with the data available in the literature.⁹ N,N-Dimethyl-2-((4-(trifluoromethyl)phenyl)amino)acetamide (1l): G Purification by column chromatography (hexane/EtOAc, 50:50) af nd (143 mg, 58%) as a colorless solid.1H NMR (500 MHz, CDCl3) δ 7. , . , , H⁵), 6.62 (d, J = 8.5 Hz, 2H, H⁴), 5.29 (br s, 1H, H³), 3.87 (s, 2H, H²), 3.05 (s, 6H, H¹). The spectroscopic properties were consistent with the data available in the literature.⁹ 2-((4-Fluoro-3-methoxyphenyl)amino)-N,N-dimethylacetamide (1m): Purification by column chromatography (hexane/EtOAc, 50:50) (129 mg, 57%) as a colorless solid. m.p. = 105 – 107 °C (hexane/EtOAc); IR (thin film) ν_max/cm⁻¹: 3384 (br), 2933 (s), 1652 (s), 1520 (s), 1225 (s); 1H NMR (500 MHz, CDCl₃) δ 6.90 – 6.86 (m, 1H, H⁹), 6.28 – 6.26 (m, 1H, H¹⁰), 6.06 – 6.03 (m, 1H, H⁵), 4.77 (br s, 1H, H³), 3.84 (s, 3H, H⁷), 3.80 (s, 2H, H²), 3.01 (s, 6H, H¹); 13C NMR (126 MHz, CDCl3) δ 168.8 (C=O), 148.0 (d, J = 11.5 Hz, C⁶), 145.7 (d, J = 234.5 Hz, C⁸), 144.4 (C⁴), 116.1 (d, J = 19.0 Hz, C⁹), 103.2 (d, J = 6.5 Hz, C¹⁰), 99.6 (C⁵), 56.1 (C⁷), 45.6 (C²), 35.7 (C¹), 35.6 (C^1’); ¹⁹F NMR (471 MHz, CDCl₃) δ -149.8; HRMS (ESl): calculated for C₁₁H₁₅FN₂O₂Na [M+Na]⁺ requires m/z 249.1010, found m/z 249.1012. 2-((4-Hydroxyphenyl)amino)-1-morpholinoethan-1-one (1n): General procedure A: Purification by column chromatography (hexane/EtOAc, 50:50) afforded the title compound (135 mg, 57%) as a pale-yellow solid. m.p. = 178 – 180 °C (hexane/EtOAc); IR (thin film) νmax/cm⁻¹: 3352 (br), 2860 (s), 1636 (s), 1517 (s), 1440 (s), 1114 (s); 1H NMR (500 MHz, DMSO-d⁶) δ 8.43 (s, 1H, H⁹), 6.56 – 6.50 (m, 4H, H⁶ + H⁷), 4.93 (t, J = 5.5 Hz, 1H, H⁴), 3.80 (d, J = 5.0 Hz, 2H, H³), 3.60 – 3.55 (m, 4H, H¹), 3.49 – 3.45 (m, 4H, H²); 13C NMR (126 MHz, DMSO-d⁶) δ 168.4 (C=O), 148.6 (C⁸), 141.1 (C⁵), 115.6 (C⁷), 113.8 (C⁶), 66.1 (C¹), 66.0 (C^1’), 45.6 (C³), 44.5 (C²), 41.7 (C^2’); HRMS (ESl): calculated for C12H17N2O3 [M+H]⁺ requires m/z 237.1234, found m/z 237.1231. 2-((4-Hydroxyphenyl)amino)-N-phenylacetamide (1o): by column chromatography (hexane/EtOAc, 35:65) (148 mg, 61%) as a colorless solid. m.p. = 174 – 176 °C (hexane/EtOAc); IR (thin film) ν /cm⁻¹: 3312 ( 1 max br), 1660 (s), 1598 (s), 1513 (s), 1243 (s); H NMR (500 MHz, CD3OD-d⁴) δ 7.55 (d, J = 7.5 Hz, 2H, H³), 7.33 – 7.30 (m, 2H, H²), 7.13 – 7.10 (m, 1H, H¹), 6.68 (d, J = 9.0 Hz, 2H, H⁸), 6.59 (d, J = 9.0 Hz, 2H, H⁷), 3.83 (s, 2H, H⁵); 13C NMR (126 MHz, CD3OD-d⁴) δ 171.2 (C=O), 149.7 (C⁹), 141.1 (C⁶), 137.8 (C⁴), 128.4 (C²), 124.1 (C¹), 120.0 (C³), 115.6 (C⁸), 114.4 (C⁷), 49.4 (C⁵); HRMS (ESl): calculated for C₁₄H₁₄N₂O₂Na [M+Na]⁺ requires m/z 265.0947, found m/z 265.0954. N,N-Dimethyl-3-(phenylamino)propanamide (1p): Amide 1p was prepared by reported procedure.¹⁰ flask was charged with aniline (93.1 mg, 1.00 mmol, 100 mol%), N,N-dimethylacrylamide (129 mg, 1.30 mmol, 130 mol%) and imidazolium chloride (31.2 mg, 0.30 mmol, 30 mol%) at r.t. After the addition was complete, the reaction mixture was stirred at 120 °C for 4 hours and the progress of the reaction was monitored by TLC. Upon completion, the reaction was cooled to r.t. and then was transferred to a separatory funnel and water (approx. 10.0 mL) was added. The aqueous phase was extracted with EtOAc (approx. 3 × 5.0 mL). The combined organic phases were dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (hexane/EtOAc, 50:50) afforded the title compound (96.1 mg, 50%) as a colorless solid.1H NMR (500 MHz, CDCl₃) δ 7.18 – 7.15 (m, 2H, H⁷), 6.71 – 6.68 (m, 1H, H⁸), 6.63 (d, J = 7.5 Hz, 2H, H⁶), 4.34 (br s, 1H, H⁴), 3.49 (t, J = 6.0 Hz, 2H, H³), 2.96 – 2.95 (m, 6H, H¹), 2.59 (t, J = 6.0 Hz, 2H, H²). The spectroscopic properties were consistent with the data available in the literature.¹⁰ 1-Phenyl-2-(phenylamino)ethan-1-one (1q): Ketone 1q was prepared by the reported procedure.¹¹ flask was charged with aniline (93.1 mg, 1.00 mmol, 100 mol%), mmol, 100 mol%) and EtOH (5.0 mL) at r.t.2-Bromo-1-phenylethan- 1- mmol, 100 mol%) in EtOH (2.0 mL) was then added dropwise to the stirring solution over 3 minutes at r.t. After the addition was complete, the reaction mixture was stirred for 12 hours at r.t. and the progress of the reaction was monitored by TLC. Upon completion, the crude product could be obtained as a yellow precipitate, which was recrystallized from EtOH affording the title compound (158 mg, 75%) as a pale-yellow solid. 1H NMR (500 MHz, CDCl₃) δ 8.04 (d, J = 7.0 Hz, 2H, H³), 7.65 – 7.62 (m, 1H, H¹), 7.54 – 7.51 (m, 2H, H²), 7.26 – 7.22 (m, 2H, H⁸), 6.78 – 6.72 (m, 3H, H⁷ + H⁹), 5.03 (br s, 1H, H⁴), 4.63 (s, 2H, H⁵). The spectroscopic properties were consistent with the data available in the literature.¹¹ General procedure B for the synthesis of ketones 1r-1s: Ketones 1r-1s were synthesized according to a modified procedure.¹² mg, 1.00 mmol, 100 mol%), K₂CO₃ (207 mg, 1.50 mmol, 150 mol%) and acetone (5.0 mL) and was stirred at 60 °C. After 1 hour, bromide ketone (1.00 mmol, 100 mol%) was then added dropwise to the stirring solution over 3 minutes at r.t. After the addition was complete, the reaction mixture was stirred for 20 hours at 60 °C and the progress of the reaction was monitored by TLC. Upon completion, the mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by FCC under the conditions noted. 1-(Phenylamino)propan-2-one (1r): General procedure B: Purification by column chromatography (hexane/EtOAc, 85:15) afforded the title compound (89.4 mg, 60%) as a brown solid.1H NMR (500 MHz, CDCl3) 7.22 – 7.19 (m, 2H, H⁵), 6.76 – 6.73 (m, 1H, H⁶), 6.60 (d, J = 7.5 Hz, 2H, H⁴), 4.57 (br s, 1H, H³), 4.00 (d, J = 4.5 Hz, 2H, H²), 2.25 (s, 3H, H¹). The spectroscopic properties were consistent with the data available in the literature.¹² 3,3-Dimethyl-1-(phenylamino)butan-2-one (1s): B: Purification by column chromatography (hexane/EtOAc, 90:10) (15 1 5 mg, 81%) as a colorless solid. H NMR (500 MHz, CDCl₃) 7.22 – 7.19 (m, 2H, H⁵), 6.75 – 6.72 (m, 1H, H⁶), 6.64 (d, J = 7.5 Hz, 2H, H⁴), 4.76 (br s, 1H, H³), 4.12 (s, 2H, H²), 1.24 (s, 9H, H¹). The spectroscopic properties were consistent with the data available in the literature.¹³ Alkenes: Styrene, simple substituted styrenes, vinyl ferrocene and α-olefins were purchased and used as received. Alkenes tosyl-3-vinyl-1H-indole 2a, vinylbenzyl 2-(1-(4-chlorobenzoyl)-5-methoxy-2- methyl-1H-indol-3-yl)acetate 2b and tert-butyl(hex-5-en-1-yloxy)dimethylsilane 2c were prepared by reported procedures.^14-16 1-Tosyl-3-vinyl-1H-indole (2a): (s, H¹³), 1H, 4-Vinylbenzyl 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetate (2b): (d, J 2H, H¹⁸), (m, , = , – , – + H⁶), 0.89 (s, 9H, H¹), 0.05 (s, 6H, H³). The spectroscopic properties were consistent with the data available in the literature.¹⁶ Coupling reactions General procedure C for asymmetric alkylation: A Schlenk tube was charged with substrate (0.10 mmol, 100 mol%), [Ir(cod)2]BARF (6.36 mg, 5.00 μmol, 5 mol%), (R)-SEGPHOS (3.05 mg, 5.00 μmol, 5 mol%) and styrene derivative (if non-volatile, 200 mol%). The Schlenk tube was evacuated and refilled with N₂ (three cycles), then the alkene partner (if volatile, 200-1000 mol%) was added followed by anhydrous 1,4- dioxane (0.2 mL, 0.5 M). The tube was sealed and heated at 130 °C for 72 hours. After cooling to r.t., the solvent was removed under reduced pressure and the crude reaction mixture was purified by FCC. The racemic products were also obtained using the above procedure (rac- BINAP was used in place of (R)-SEGPHOS) and purified by FCC. (2S,3S)-N,N-Dimethyl-3-phenyl-2-(phenylamino)butanamide (3a): Ge The reaction was carried out with substrate 1a (17.8 mg, 0.10 mmol, 10 (23.0 µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/ tO c 0:30) afforded the title compound (23.1 mg, 82%, >30:1 B:L, d.r. = 18:1 a:b, e.r. = 97.5:2.5) as a pale-yellow solid.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 10:1. m.p. = 103 – 105 °C (hexane/EtOAc); [^]^ ^^ = -7.8 (c = 1.0, CHCl₃); IR (thin film) ν_max/cm⁻¹: 3335 (br), 3027 (s), 2931 (s), 1638 (s), 1602 (s), 1495 (s), 699 (s); 1H NMR (500 MHz, CDCl₃) Data for the major diastereomer a: δ 7.35 – 7.25 (m, 5H, H¹² + H¹³ + H¹⁴), 7.20 – 7.16 (m, 2H, H⁷), 6.75 – 6.72 (m, 1H, H⁸), 6.66 (d, J = 7.5 Hz, 2H, H⁶), 5.32 – 4.13 (m, 2H, H³ + H⁴), 3.39 – 3.34 (m, 1H, H⁹), 2.92 (s, 3H, H¹), 2.66 (s, 3H, H^1’), 1.40 (d, J = 7.0 Hz, 3H, H¹⁰). Characteristic signals for the minor diastereomer b: 2.76 (s, 3H, H¹), 2.64 (s, 3H, H^1’), 1.49 (d, J = 7.0 Hz, 3H, H¹⁰);13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 171.5 (C²), 146.9 (C⁵), 142.5 (C¹¹), 129.3 (C⁷), 128.4 (C¹³), 127.9 (C¹²), 126.9 (C¹⁴), 117.9 (C⁸), 113.9 (C⁶), 58.1 (C³), 42.3 (C⁹), 36.8 (C¹), 35.6 (C^1’), 15.7 (C¹⁰); HRMS (ESl): calculated for C18H22N2ONa [M+Na]⁺ requires m/z 305.1624, found m/z 305.1627; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO2:i-PrOH 90:10, 2.0 mL/min, 145 bar, 40 °C. Retention times: 6.7 mins (major), 7.2 mins (minor), e.r. = 97.5:2.5. To facilitate analysis by SFC, the major diastereomer was separated from the minor diastereoisomer by FCC. (2S,3S)-N-Methyl-3-phenyl-2-(phenylamino)butanamide (3b): General procedure C: The reaction was carried out with substrate 1b (16.4 mg, 0.10 mmol, 100 mol%) and styrene (23.0 µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 60:40) afforded the title compound (14.5 mg, 54%, >30:1 B:L, d.r. = 18:1 a:b, e.r. = 96:4) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 7:1. [^]^^ ^ = +50.3 (c = 1.0, CHCl3); IR (thin film) νmax/cm⁻¹: 3308 (br), 2928 (s), 1650 (s), 1603 (s), 1504 (s), 1316 (s), 700 (s); 1H NMR (500 MHz, CDCl₃) Data for the major diastereomer a: δ 7.39 – 7.26 (m, 5H, H¹³ + H¹⁴ + H¹⁵), 7.20 – 7.17 (m, 2H, H⁸), 6.82 – 6.79 (m, 1H, H⁹), 6.57 (d, J = 8.0 Hz, 2H, H⁷), 6.53 (br s, 1H, H²), 4.14 – 3.72 (m, 2H, H⁴ + H⁵), 3.57 – 3.51 (m, 1H, H¹⁰), 2.76 (d, J = 4.5 Hz, 3H, H¹), 1.46 (d, J = 7.0 Hz, 3H, H¹¹). Characteristic signals for the minor diastereomer b: 2.80 (d, J = 4.5 Hz, 2H, H¹), 1.43 (d, J = 7.0 Hz, 2H, H¹¹); 13C NMR (126 MHz, CDCl₃) Data for the major diastereomer a only: δ 173.2 (C²), 146.8 (C⁶), 141.2 (C¹²), 129.4 (C⁸), 128.9 (C¹⁴), 127.6 (C¹³), 127.3 (C¹⁵), 119.1 (C⁹), 113.7 (C⁷), 64.6 (C⁴), 42.1 (C¹⁰), 26.0 (C¹), 18.4 (C¹¹); HRMS (ESl): calculated for C17H20N2ONa [M+Na]⁺ requires m/z 291.1468, found m/z 291.1482; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO2:i-PrOH 90:10, 2.0 mL/min, 140 bar, 40 °C. Retention times: 12.3 mins (major), 13.6 mins (minor), e.r. = 96:4. To facilitate analysis by SFC, the major diastereomer was separated from the minor diastereoomer by FCC. (2S,3S)-N,N-Diethyl-3-phenyl-2-(phenylamino)butanamide (3c): reaction was carried out with substrate 1c (20.6 mg, 0.10 mmol, µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 65:35) afforded the title compound (26.1 mg, 84%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 98:2) as a colorless solid.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 5:1. m.p. = 60 – 62 °C (hexane/EtOAc); [^]^ ^^ = -42.2 (c = 1.0, CHCl₃); IR (thin film) ν_max/cm⁻¹: 3334 (br), 2973 (s), 2933 (s), 1631 (s), 1601 (s), 1496 (s), 750 (s), 699 (s); 1H NMR (500 MHz, CDCl₃) Data for the major diastereomer a only: δ 7.33 – 7.23 (m, 5H, H¹³ + H¹⁴ + H¹⁵), 7.17 – 7.14 (m, 2H, H⁸), 6.72 – 6.69 (m, 1H, H⁹), 6.63 (d, J = 7.5 Hz, 2H, H⁷), 4.60 – 4.32 (m, 2H, H⁴ + H⁵), 3.68 – 3.61 (m, 1H, H²), 3.36 – 3.30 (m, 1H, H¹⁰), 3.12 – 3.03 (m, 2H, H^2’), 2.94 – 2.86 (m, 1H, H²), 1.41 (d, J = 7.0 Hz, 3H, H¹¹), 1.12 (t, J = 7.0 Hz, 3H, H¹), 1.02 (t, J = 7.0 Hz, 3H, H^1’); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 170.7 (C³), 147.1 (C⁶), 142.6 (C¹²), 129.2 (C⁸), 128.3 (C¹⁴), 128.1 (C¹³), 126.9 (C¹⁵), 117.8 (C⁹), 114.0 (C⁷), 58.5 (C⁴), 42.6 (C¹⁰), 41.4 (C²), 40.3 (C^2’), 16.1 (C¹¹), 14.3 (C¹), 12.8 (C^1’); HRMS (ESl): calculated for C₂₀H₂₆N₂ONa [M+Na]⁺ requires m/z 333.1937, found m/z 333.1948; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO₂:i-PrOH 98:2, 2.0 mL/min, 140 bar, 40 °C. Retention times: 18.7 mins (minor), 23.9 mins (major), e.r. = 98:2. (2S,3S)-3-Phenyl-2-(phenylamino)-1-(pyrrolidin-1-yl)butan-1-one (3d): Ge The reaction was carried out with substrate 1d (20.4 mg, 0.10 mmol, 10 (23.0 µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 60:40) afforded the title compound (21.3 mg, 69%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 98:2) as a colorless solid.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 9:1. m.p. = 115 – 117 °C (hexane/EtOAc); [^]^ ^^ = -34.3 (c = 1.0 CHCl₃); IR (thin film) ν_max/cm⁻¹: 3335 (br), 3006 (s), 2989 (s), 1631 (s), 1602 (s), 1261 (s), 766 (s); 1H NMR (500 MHz, CDCl₃) Data for the major diastereomer a only: δ 7.32 – 7.21 (m, 5H, H¹³ + H¹⁴ + H¹⁵), 7.17 – 7.14 (m, 2H, H⁸), 6.73 – 6.70 (m, 1H, H⁹), 6.65 (d, J = 8.0 Hz, 2H, H⁷), 4.78 (br s, 1H, H⁵), 4.36 (d, J = 6.0 Hz, 1H, H⁴), 3.49 – 3.44 (m, 1H, H²), 3.41 – 3.34 (m, 2H, H² + H¹⁰), 3.25 – 3.20 (m, 1H, H^2’), 2.59 – 2.55 (m, 1H, H^2’), 1.77 – 1.56 (m, 4H, H¹), 1.39 (d, J = 7.0 Hz, 3H, H¹¹); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 169.7 (C³), 146.6 (C⁶), 142.7 (C¹²), 129.3 (C⁸), 128.4 (C¹⁴ ), 127.9 (C¹³), 126.9 (C¹⁵), 118.0 (C⁹), 113.9 (C⁷), 60.4 (C⁴), 46.3 (C²), 45.8 (C^2’), 42.0 (C¹⁰), 25.6 (C¹), 23.9 (C^1’), 15.4 (C¹¹); HRMS (ESl): calculated for C20H24N2ONa [M+Na]⁺ requires m/z 331.1781, found m/z 331.1788; Chiral SFC: YMC Chiral ART Cellulose-SB column (25 cm), CO2:i-PrOH 95:5, 2.0 mL/min, 140 bar, 40 °C. Retention times: 25.3 mins (minor), 28.2 mins (major), e.r. = 98:2. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-3-Phenyl-2-(phenylamino)-1-(piperidin-1-yl)butan-1-one (3e): General procedure C: The reaction was carried out with substrate 1e (21.8 mg, 0.10 mmol, 100 mol%) and styrene (23.0 µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 60:40) afforded the title compound (25.1 mg, 78%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 94.5:5.5) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 4:1. [^]^ ^^ = -3.2 (c = 1.0 CHCl₃); IR (thin film) ν_max/cm⁻¹: 3336 (br), 2935 (s), 2855 (s), 1627 (s), 1601 (s), 1495 (s), 1249 (s), 793 (s); 1H NMR (500 MHz, CDCl3) Data for the major diastereomer a only: δ 7.35 – 7.17 (m, 5H, H¹⁴ + H¹⁵ + H¹⁶), 7.19 – 7.15 (m, 2H, H⁹), 6.74 – 6.71 (m, 1H, H¹⁰), 6.65 (d, J = 7.5 Hz, 2H, H⁸), 4.74 – 4.39 (m, 2H, H⁵ + H⁶), 3.70 – 3.66 (m, 1H, H³), 3.45 – 3.29 (m, 3H, H³ + H¹¹), 3.12 – 3.07 (m, 1H, H³), 1.65 – 1.46 (m, 5H, H¹), 1.41 (d, J = 7.0 Hz, 3H, H¹²), 1.38 – 1.32 (m, 1H, H¹); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 170.0 (C⁴), 147.2 (C⁷), 142.4 (C¹³), 129.2 (C⁹), 128.4 (C¹⁵), 128.0 (C¹⁴), 126.8 (C¹⁶), 117.9 (C¹⁰), 113.9 (C⁸), 58.1 (C⁵), 46.5 (C³), 43.1 (C^3’), 42.4 (C¹¹), 26.2 (C²), 25.5 (C^2’), 24.4 (C¹), 16.7 (C¹²); HRMS (ESl): calculated for C21H26N2ONa [M+Na]⁺ requires m/z 345.1937, found m/z 345.1951; Chiral SFC: DAICEL CHIRALCEL OD- H column (25 cm), CO2:i-PrOH 90:10, 2.0 mL/min, 140 bar, 40 °C. Retention times: 6.5 mins (minor), 8.2 mins (major), e.r. = 94.5:5.5. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-1-Morpholino-3-phenyl-2-(phenylamino)butan-1-one (3f): reaction was carried out with substrate 1f (22.0 mg, 0.10 mmol, µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 60:40) afforded the title compound (22.0 mg, 68%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 98:2) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 5:1. [^]^^ ^ = -15.9 (c = 1.0 CHCl₃); IR (thin film) ν_max/cm⁻¹: 3344 (br), 2922 (s), 2854 (s), 1635 (s), 1601 (s), 1495 (s), 1423 (s), 1113 (s); 1H NMR (500 MHz, CDCl3) Data for the major diastereomer a only: δ 7.35 – 7.24 (m, 5H, H¹³ + H¹⁴ + H¹⁵), 7.18 – 7.15 (m, 2H, H⁸), 6.74 – 6.71 (m, 1H, H⁹), 6.64 (d, J = 7.5 Hz, 2H, H⁷), 4.56 – 4.47 (m, 2H, H⁴ + H⁵), 3.63 – 3.50 (m, 4H, H¹), 3.43 – 3.26 (m, 3H, H² + H¹⁰), 3.22 – 3.18 (m, 1H, H^2’), 3.00 – 2.95 (m, 1H, H^2’), 1.39 (d, J = 7.0 Hz, 3H, H¹¹); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 170.2 (C³), 146.7 (C⁶), 142.2 (C¹²), 129.4 (C⁸), 128.6 (C¹⁴), 128.0 (C¹³), 127.1 (C¹⁵), 118.3 (C⁹), 113.9 (C⁷), 66.7 (C¹), 66.1 (C^1’), 57.9 (C⁴), 46.0 (C²), 42.3 (C^2’), 42.0 (C¹⁰), 15.7 (C¹¹); HRMS (ESl): calculated for C₂₀H₂₄N₂O₂Na [M+Na]⁺ requires m/z 347.1730, found m/z 347.1742; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO₂:i-PrOH 90:10, 2.0 mL/min, 140 bar, 40 °C. Retention times: 8.7 mins (minor), 10.9 mins (major), e.r. = 98:2. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-2-((4-Hydroxyphenyl)amino)-N,3-diphenylbutanamide (3o): Ge e reaction was carried out with substrate 1o (24.2 mg, 0.10 mmol, 10 3.0 µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 65:35) afforded the title compound (23.9 mg, 69%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 91:9) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 4:1. [^]^ ^^ = -27.4 (c = 1.0 CHCl₃); IR (thin film) ν_max/cm⁻¹: 3320 (br), 2928 (s), 1669 (s), 1599 (s), 1512 (s), 1444 (s), 1238 (s), 756 (s), 702 (s); 1H NMR (500 MHz, CD3OD-d⁴) Data for the major diastereomer a only: δ 7.47 (d, J = 8.0 Hz, 2H, H³), 7.32 – 7.18 (m, 7H, H² + H¹⁴ + H¹⁵ + H¹⁶), 7.11 – 7.08 (m, 1H, H¹), 6.58 (d, J = 8.5 Hz, 2H, H⁹), 6.49 (d, J = 8.5 Hz, 2H, H⁸), 3.97 (d, J = 8.0 Hz, 1H, H⁶), 3.27 – 3.21 (m, 1H, H¹¹), 1.39 (d, J = 7.0 Hz, 3H, H¹²);13C NMR (126 MHz, CD₃OD-d⁴) Data for the major diastereomer a only: δ 173.5 (C⁵), 149.7 (C¹⁰), 142.8 (C⁷), 140.5 (C¹³), 137.7 (C⁴), 128.4 (C²), 128.3 (C¹⁵), 127.4 (C¹⁴), 126.6 (C¹⁶), 124.2 (C¹), 120.3 (C³), 115.5 (C⁹), 115.2 (C⁸), 66.0 (C⁶), 43.1 (C¹¹), 18.0 (C¹²); HRMS (ESl): calculated for C22H22N2O2Na [M+Na]⁺ requires m/z 369.1573, found m/z 369.1583; Chiral SFC: DAICEL CHIRALCEL IE column (25 cm), CO₂:i-PrOH (with 0.5% TEA) 70:30, 2.0 mL/min, 190 bar, 40 °C. Retention times: 4.9 mins (major), 5.8 mins (minor), e.r. = 91:9. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-1,3-Diphenyl-2-(phenylamino)butan-1-one (3q): General procedure C: The reaction was carried out with substrate 1q (21.1 mg, 0.10 mmol, 100 mol%), styrene (23.0 µL, 0.20 mmol, 200 mol%) and (R)-3,5-(t-Bu)₂-H₈-BINAP (5.40 mg, 5.00 μmol, 5 mol%) at 90 ^oC. Purification of the residue by FCC (hexane/EtOAc 95:5) afforded the title compound (26.8 mg, 85%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 71:29) as a pale-yellow oil. ¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 8:1. [^]^ ^^ = +28.6 (c = 1.0 CHCl₃); IR (thin film) ν_max/cm⁻¹: 3379 (br), 3027 (s), 1682 (s), 1601 (s), 1506 (s), 748 (s), 693 (s); 1H NMR (500 MHz, CD2Cl2) Data for the major diastereomer a only: δ 7.93 (d, J = 7.5 Hz, 2H, H³), 7.61 – 7.58 (m, 1H, H¹), 7.49 – 7.46 (m, 2H, H²), 7.26 – 7.18 (m, 3H, H¹⁶ + H¹⁷), 7.12 – 7.08 (m, 4H, H¹⁰ + H¹⁵), 6.68 – 6.65 (m, H⁹ + H¹¹), 5.19 (d, J = 5.0 Hz, 1H, H⁶), 4.37 (br s, 1H, H⁷), 3.45 – 3.40 (m, 1H, H¹²), 1.44 (d, J = 7.0 Hz, 3H, H¹³);13C NMR (126 MHz, CD2Cl2) Data for the major diastereomer a only: δ 200.4 (C⁵), 147.8 (C⁸), 141.4 (C¹⁴), 136.3 (C⁴), 133.5 (C¹), 129.3 (C¹⁰), 128.9 (C³), 128.4 (C¹⁶), 128.3 (C²), 128.2 (C¹⁵), 127.0 (C¹⁷), 118.2 (C¹¹), 114.0 (C⁹), 63.5 (C⁶), 42.9 (C¹²), 18.2 (C¹³); HRMS (ESl): calculated for C₂₂H₂₁NONa [M+Na]+ requires m/z 338.1515, found m/z 338.1524; Chiral SFC: DAICEL CHIRALCEL IE column (25 cm), CO2:i-PrOH 95:5, 1.0 mL/min, 140 bar, 40 °C. Retention times: 42.8 mins (minor), 53.1 mins (major), e.r. = 71:29. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (3S,4S)-4-Phenyl-3-(phenylamino)pentan-2-one (3r): The reaction was carried out with substrate 1r (14.9 mg, 0.10 mmol, , µL, 0.20 mmol, 200 mol%) and (R)-DTBM-SEGPHOS (5.90 mg, 5.00 μmol, 5 mol%) and was run for 22 hours at 90 ^oC. Purification of the residue by FCC (hexane/EtOAc 85:15) afforded the title compound (17.7 mg, 70%, >30:1 B:L, d.r. = 9:1 a:b, e.r. = 90:10) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 2:1. [^]^^ ^ = -1.5 (c = 1.0 CHCl3); IR (thin film) νmax/cm⁻¹: 3378 (br), 2934 (s), 1709 (s), 1603 (s), 1506 (s), 751 (s), 701 (s); 1H NMR (500 MHz, CDCl3) Data for the major diastereomer a: δ 7.39 – 7.27 (m, 5H, H¹² + H¹³ + H¹⁴), 7.17 – 7.14 (m, 2H, H⁷), 6.75 – 6.72 (m, 1H, H⁸), 6.54 (d, J = 7.5 Hz, 2H, H⁶), 4.19 – 3.89 (m, 2H, H³ + H⁴), 3.30 – 3.24 (m, 1H, H⁹), 2.06 (s, 3H, H¹), 1.37 (d, J = 7.0 Hz, 3H, H¹⁰). Characteristic signals for the minor diastereomer b: 6.47 (d, J = 7.5 Hz, 2H, H⁶), 1.99 (s, 3H, H¹), 1.42 (d, J = 7.0 Hz, 3H, H¹⁰); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 211.3 (C²), 146.9 (C⁵), 141.5 (C¹¹), 129.4 (C⁷), 128.9 (C¹³), 127.6 (C¹²), 127.4 (C¹⁴), 118.3 (C⁸), 113.2 (C⁶), 69.2 (C³), 41.5 (C⁹), 26.7 (C¹), 18.2 (C¹⁰); HRMS (ESl): calculated for C17H19NONa [M+Na]⁺ requires m/z 276.1359, found m/z 276.1361; Chiral SFC: DAICEL CHIRALCEL IE column (25 cm), CO2:i- PrOH 95:5, 1.0 mL/min, 140 bar, 40 °C. Retention times: 12.9 mins (major), 14.2 mins (minor), e.r. = 90:10. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (4S,5S)-2,2-Dimethyl-5-phenyl-4-(phenylamino)hexan-3-one (3s): Ge The reaction was carried out with substrate 1s (19.1 mg, 0.10 mmol, 10 .0 µL, 0.20 mmol, 200 mol%) and (R)-DTBM-SEGPHOS (5.90 mg, 5.00 μmol, 5 mol%). Purification of the residue by FCC (hexane/EtOAc 90:10) afforded the title compound (21.3 mg, 72%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 74.5:25.5) as a pale-yellow oil. ¹H NMR analysis of the crude material gave ^^ ^ = +51.5 (c = 1.0 CHCl3); IR (thin film) νmax/cm⁻¹: 3338 (br), 1513 (s), 1314 (s), 1060 (s), 699 (s); 1H NMR (500 MHz, CDCl3) a only: δ 7.34 – 7.21 (m, 5H, H¹³ + H¹⁴ + H¹⁵), 7.17 – 7.14 (m, 2H, H⁸), 6.73 – 6.70 (m, 1H, H⁹), 6.59 (d, J = 8.0 Hz, 2H, H⁷), 4.59 (d, J = 8.0 Hz, 1H, H⁴), 4.08 (br s, 1H, H⁵), 3.31 – 3.25 (m, 1H, H¹⁰), 1.39 (d, J = 7.0 Hz, 3H, H¹¹), 0.87 (s, 9H, H¹); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 215.5 (C³), 147.3 (C⁶), 143.3 (C¹²), 129.3 (C⁸), 128.5 (C¹⁴), 128.2 (C¹³), 126.8 (C¹⁵), 118.0 (C⁹), 113.6 (C⁷), 62.3 (C⁴), 43.4 (C²), 42.7 (C¹⁰), 25.9 (C¹), 16.3 (C¹¹); HRMS (ESl): calculated for C₂₀H₂₆NO [M+H]⁺ requires m/z 296.2009, found m/z 296.2016; Chiral SFC: DAICEL CHIRALCEL IE column (25 cm), CO₂:i-PrOH 95:5, 1.0 mL/min, 140 bar, 40 °C. Retention times: 9.8 mins (major), 10.8 mins (minor), e.r. = 74.5:25.5. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-2-((4-Hydroxyphenyl)amino)-N,N-dimethyl-3-phenylbutanamide (3g): General procedure C: The reaction was carried out with substrate 1g (19.4 mg, 0.10 mmol, 100 mol%) and styrene (23.0 µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 65:35) afforded the title compound (25.9 mg, 87%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 98:2) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 6:1. [^]^ ^^ = -11.8 (c = 1.0 CHCl3); IR (thin film) νmax/cm⁻¹: 3331 (br), 3027 (s), 2968 (s), 1623 (s), 1514 (s), 1240 (s), 700 (s); 1H NMR (500 MHz, CDCl₃) Data for the major diastereomer a only: δ 7.34 – 7.23 (m, 5H, H¹² + H¹³ + H¹⁴), 6.64 (d, J = 8.0 Hz, 2H, H⁷), 6.50 (d, J = 8.0 Hz, 2H, H⁶), 4.60 – 3.61 (m, 2H, H³ + H⁴), 3.30 – 3.24 (m, 1H, H⁹), 2.89 (s, 3H, H¹), 2.72 (s, 3H, H^1’), 1.38 (d, J = 7.0 Hz, 3H, H¹⁰); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 172.7 (C²), 149.4 (C⁸), 142.6 (C⁵), 140.2 (C¹¹), 128.4 (C¹³), 127.8 (C¹²), 126.8 (C¹⁴), 116.4 (C⁷), 116.2 (C⁶), 60.3 (C³), 42.5 (C⁹), 37.0 (C¹), 35.8 (C^1’), 16.3 (C¹⁰); HRMS (ESl): calculated for C₁₈H₂₂N₂O₂Na [M+Na]⁺ requires m/z 321.1573, found m/z 321.1583; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO₂:i-PrOH 85:15, 2.0 mL/min, 160 bar, 40 °C. Retention times: 10.2 mins (major), 11.2 mins (minor), e.r. = 98:2. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-2-((4-Methoxyphenyl)amino)-N,N-dimethyl-3-phenylbutanamide (3h): reaction was carried out with substrate 1h (20.8 mg, 0.10 mmol, µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 65:35) afforded the title compound (17.2 mg, 55%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 90.5:9.5) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 9:1. [^]^{^} _^ ^{^} = -5.8 (c = 1.0 CHCl₃); IR (thin film) ν_max/cm⁻¹: 3334 (br), 2931 (s), 1637 (s), 1510 (s), 1236 (s), 701 (s); 1H NMR (500 MHz, CDCl3) Data for the major diastereomer a only: δ 7.35 – 7.24 (m, 5H, H¹³ + H¹⁴ + H¹⁵), 6.77 (d, J = 9.0 Hz, 2H, H⁷), 6.62 (d, J = 9.0 Hz, 2H, H⁶), 4.61 – 3.89 (m, 2H, H³ + H⁴), 3.75 (s, 3H, H⁹), 3.34 – 3.28 (m, 1H, H¹⁰), 2.91 (s, 3H, H¹), 2.68 (s, 3H, H^1’), 1.39 (d, J = 7.0 Hz, 3H, H¹¹); 13C NMR (126 MHz, CDCl₃) Data for the major diastereomer a only: δ 171.9 (C²), 152.6 (C⁸), 142.7 (C⁵), 141.1 (C¹²), 128.4 (C¹⁴), 127.8 (C¹³), 126.8 (C¹⁵), 115.9 (C⁷), 114.8 (C⁶), 59.8 (C³), 55.7 (C⁹), 42.4 (C¹⁰), 36.8 (C¹), 35.6 (C^1’), 16.0 (C¹¹); HRMS (ESl): calculated for C19H24N2O2Na [M+Na]⁺ requires m/z 335.1730, found m/z 335.1739; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO2:i-PrOH 90:10, 2.0 mL/min, 140 bar, 40 °C. Retention times: 6.9 mins (minor), 8.3 mins (major), e.r. = 90.5:9.5. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-N,N-Dimethyl-3-phenyl-2-(p-tolylamino)butanamide (3i): General procedure C: The reaction was carried out with substrate 1i (19.2 mg, 0.10 mmol, 100 mol%) and styrene (23.0 µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 65:35) afforded the title compound (26.4 mg, 89%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 97:3) as a pale-yellow solid.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 8:1. m.p. = 103 – 105 °C (hexane/EtOAc); [^]^ ^^ = -10.9 (c = 1.0 CHCl₃); IR (thin film) ν /cm⁻¹: 3333 (br), 2923 (s), 1639 (s), 1520 (s), 1396 (s), 1055 (s), 701 (s) 1 max ; H NMR (500 MHz, CDCl₃) Data for the major diastereomer a only: δ 7.35 – 7.24 (m, 5H, H¹³ + H¹⁴ + H¹⁵), 6.99 (d, J = 8.5 Hz, 2H, H⁷), 6.59 (d, J = 8.5 Hz, 2H, H⁶), 4.71 – 4.31 (m, 2H, H³ + H⁴), 3.38 – 3.32 (m, 1H, H¹⁰), 2.91 (s, 3H, H¹), 2.66 (s, 3H, H^1’), 2.25 (s, 3H, H⁹), 1.40 (d, J = 7.0 Hz, 3H, H¹¹); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 171.6 (C²), 144.6 (C⁵), 142.6 (C¹²), 129.7 (C⁷), 128.4 (C¹⁴), 127.8 (C¹³), 127.2 (C¹⁵), 126.8 (C⁸), 114.2 (C⁶), 58.6 (C³), 42.2 (C¹⁰), 36.8 (C¹), 35.5 (C^1’), 20.3 (C⁹), 15.8 (C¹¹); HRMS (ESl): calculated for C₁₉H₂₄N₂ONa [M+Na]⁺ requires m/z 319.1781, found m/z 319.1795; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO₂:i-PrOH 90:10, 2.0 mL/min, 140 bar, 40 °C. Retention times: 5.8 mins (minor), 7.1 mins (major), e.r. = 97:3. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-2-((4-Fluorophenyl)amino)-N,N-dimethyl-3-phenylbutanamide (3j): reaction was carried out with substrate 1j (19.6 mg, 0.10 mmol, 100 mol%) and styrene (23.0 µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 65:35) afforded the title compound (25.8 mg, 86%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 97.5:2.5) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 8:1. [^]^^ ^ = -2.6 (c = 1.0 CHCl3); IR (thin film) νmax/cm⁻¹: 3331 (br), 2932 (s), 1637 (s), 1509 (s), 1395 (s), 1216 (s), 823 (s), 701 (s); 1H NMR (500 MHz, CDCl3) Data for the major diastereomer a only: δ 7.33 – 7.22 (m, 5H, H¹² + H¹³ + H¹⁴), 6.86 – 6.83 (m, 2H, H⁷), 6.56 – 6.53 (m, 2H, H⁶), 4.46 (d, J = 6.5 Hz, 1H, H³), 4.35 (br s, 1H, H⁴), 3.31 – 3.25 (m, 1H, H⁹), 2.90 (s, 3H, H¹), 2.69 (s, 3H, H^1’), 1.37 (d, J = 7.0 Hz, 3H, H¹⁰); 13C NMR (126 MHz, CDCl₃) Data for the major diastereomer a only: δ 171.6 (C²), 156.1 (d, J = 236.9 Hz, C⁸), 143.4 (d, J = 1.3 Hz, C⁵), 142.4 (C¹¹), 128.4 (C¹³), 127.8 (C¹²), 126.9 (C¹⁴), 115.6 (d, J = 21.4 Hz, C⁷), 115.1 (d, J = 7.6 Hz, C⁶), 59.3 (C³), 42.4 (C⁹), 36.8 (C¹), 35.6 (C^1’), 16.1 (C¹⁰); ¹⁹F NMR (471 MHz, CDCl3) δ -126.9; HRMS (ESl): calculated for C18H21FN2ONa [M+Na]⁺ requires m/z 323.1530, found m/z 323.1548; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO2:i-PrOH 95:5, 2.0 mL/min, 140 bar, 40 Retention times: 8.7 mins (minor), 10.4 mins (major), e.r. = 97.5:2.5. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-2-((4-Chlorophenyl)amino)-N,N-dimethyl-3-phenylbutanamide (3k): reaction was carried out with substrate 1k (21.2 mg, 0.10 mmol, µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 65:35) afforded the title compound (27.8 mg, 88%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 97:3) as a pale-yellow solid.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 8:1. m.p. = 98 – 100 °C (hexane/EtOAc); [^]^ ^^ = -32.0 (c = 1.0 CHCl₃); IR (thin film) ν /cm⁻¹: 3327 (br), 2929 (s), 1635 (s), 1492 (s), 1394 (s), 816 (s) 1 max , 699 (s); H NMR (500 MHz, CDCl3) Data for the major diastereomer a only: δ 7.32 – 7.22 (m, 5H, H¹² + H¹³ + H¹⁴), 7.08 (d, J = 9.0 Hz, 2H, H⁷), 6.53 (d, J = 9.0 Hz, 2H, H⁶), 4.69 – 4.26 (m, 2H, H³ + H⁴), 3.32 – 3.27 (m, 1H, H⁹), 2.90 (s, 3H, H¹), 2.67 (s, 3H, H^1’), 1.36 (d, J = 7.0 Hz, 3H, H¹⁰); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 171.2 (C²), 145.5 (C⁵), 142.2 (C¹¹), 129.1 (C⁷), 128.4 (C¹³), 127.8 (C¹²), 127.0 (C¹⁴), 122.4 (C⁸), 114.9 (C⁶), 58.3 (C³), 42.3 (C⁹), 36.8 (C¹), 35.6 (C^1’), 15.9 (C¹⁰); HRMS (ESl): calculated for C H ClN ONa [M+N + 18 21 2 a] requires m/z 339.1235, found m/z 339.1248; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO₂:i-PrOH 95:5, 2.0 mL/min, 140 bar, 40 °C. Retention times: 6.3 mins (minor), 7.5 mins (major), e.r. = 97:3. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-N,N-Dimethyl-3-phenyl-2-((4-(trifluoromethyl)phenyl)amino)butanamide (3l): General procedure C: The reaction was carried out with substrate 1l (24.6 mg, 0.10 mmol, 100 mol%) and styrene (23.0 µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 65:35) afforded the title compound (26.3 mg, 75%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 98:2) as a pale-yellow solid.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 10:1. m.p. = 88 – 90 °C (hexane/EtOAc); [^]^{^} _^ ^{^} = -8.0 (c = 1.0 CHCl3); IR (thin film) ν /cm⁻¹: 3324 (br), 2 1 max 935 (s), 1639 (s), 1616 (s), 1324 (s), 1106 (s), 1065 (s), 701 (s); H NMR (500 MHz, CDCl3) Data for the major diastereomer a only: δ 7.39 (d, J = 8.5 Hz, 2H, H⁷), δ 7.36 – 7.25 (m, 5H, H¹³ + H¹⁴ + H¹⁵), 6.63 (d, J = 8.5 Hz, 2H, H⁶), 4.92 (br s, 1H, H⁴), 4.62 (d, J = 6.0 Hz, 1H, H³), 3.38 – 3.33 (m, 1H, H¹⁰), 2.94 (s, 3H, H¹), 2.69 (s, 3H, H^1’), 1.40 (d, J = 7.0 Hz, 3H, H¹¹); 13C NMR (126 MHz, CDCl₃) Data for the major diastereomer a only: δ 170.8 (C²), 149.4 (C⁵), 141.9 (C¹²), 128.5 (C¹⁴), 128.0 (C¹³), 127.8 (C¹⁵), 126.6 (q, J = 3.8 Hz, C⁷), 124.8 (q, J = 270.9 Hz, C⁹), 119.1 (q, J = 32.8 Hz, C⁸), 112.6 (C⁶), 57.4 (C³), 42.3 (C¹⁰), 36.9 (C¹), 35.6 (C^1’), 15.7 (C¹¹); ¹⁹F NMR (471 MHz, CDCl3) δ -61.1; HRMS (ESl): calculated for C19H21F3N2ONa [M+Na]⁺ requires m/z 373.1498, found m/z 373.1509; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO₂:i-PrOH 95:5, 2.0 mL/min, 140 bar, 40 °C. Retention times: 6.9 mins (minor), 8.8 mins (major), e.r. = 98:2. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-2-((4-Fluoro-3-methoxyphenyl)amino)-N,N-dimethyl-3-phenylbutanamide (3m): was carried out with substrate 1m (22.6 mg, 0.10 mmol, µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 65:35) afforded the title compound (27.4 mg, 83%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 96.5:3.5) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 8:1. [^]^{^} _^ ^{^} = +10.1 (c = 1.0 CHCl3); IR (thin film) νmax/cm⁻¹: 3328 (br), 2934 (s), 1636 (s), 1519 (s), 1221 (s), 1121 (s), 701 (s); 1H NMR (500 MHz, CDCl3) Data for the major diastereomer a only: δ 7.32 – 7.21 (m, 5H, H¹⁵ + H¹⁶ + H¹⁷), 6.85 – 6.81 (m, 1H, H⁷), 6.22 – 6.20 (m, 1H, H⁶), 6.08 – 6.05 (m, 1H, H¹⁰), 4.45 – 4.21 (m, 2H, H³ + H⁴), 3.79 (s, 3H, H¹¹), 3.30 – 3.25 (m, 1H, H¹²), 2.90 (s, 3H, H¹), 2.72 (s, 3H, H^1’), 1.37 (d, J = 7.0 Hz, 3H, H¹³); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 171.6 (C²), 147.9 (d, J = 11.3 Hz, C⁹), 145.8 (d, J = 235.6 Hz, C⁸), 144.0 (d, J = 2.5 Hz, C⁵), 142.3 (C¹⁴), 128.4 (C¹⁶), 127.8 (C¹⁵), 126.9 (C¹⁷), 116.0 (d, J = 18.9 Hz, C⁷), 114.5 (d, J = 6.3 Hz, C⁶), 110.9 (C¹⁰), 59.2 (C³), 56.0 (C¹¹), 42.5 (C¹²), 36.8 (C¹), 35.5 (C^1’), 16.2 (C¹³); ¹⁹F NMR (471 MHz, CDCl₃) δ - 148.7; HRMS (ESl): calculated for C19H23FN2O2Na [M+Na]⁺ requires m/z 353.1636, found m/z 353.1664; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO2:i-PrOH 90:10, 2.0 mL/min, 140 bar, 40 °C. Retention times: 6.6 mins (minor), 8.3 mins (major), e.r. = 96.5:3.5. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-2-((4-Hydroxyphenyl)amino)-1-morpholino-3-phenylbutan-1-one (3n): Ge he reaction was carried out with substrate 1n (23.6 mg, 0.10 mmol, 10 23.0 µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (he a e c ) aforded the title compound (27.6 mg, 81%, >30:1 B:L, d.r. = 15:1 a:b, e.r. = 96.5:3.5) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 4:1. [^]^ ^^ = -12.0 (c = 1.0 CHCl₃); IR (thin film) ν_max/cm⁻¹: 3337 (br), 2969 (s), 1619 (s), 1515 (s), 1452 (s), 1224 (s), 1114 (s), 701 (s); 1H NMR (500 MHz, CDCl3) Data for the major diastereomer a: δ 7.36 – 7.26 (m, 5H, H¹⁴ + H¹⁵ + H¹⁶), 6.67 (d, J = 8.5 Hz, 2H, H⁸), 6.55 (d, J = 8.5 Hz, 2H, H⁷), 5.10 (br s, 1H, H¹⁰), 4.42 (d, J = 6.5 Hz, 1H, H⁴), 4.13 (br s, 1H, H⁵), 3.67 – 3.52 (m, 4H, H¹), 3.41 – 3.24 (m, 4H, H² + H¹¹), 3.13 – 3.08 (m, 1H, H²), 1.40 (d, J = 7.0 Hz, 3H, H¹²). Characteristic signal for the minor diastereomer b: 1.52 (d, J = 7.0 Hz, 2H, H¹²); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 170.9 (C³), 148.8 (C⁹), 142.4 (C⁶), 140.7 (C¹³), 128.6 (C¹⁵), 127.9 (C¹⁴), 127.1 (C¹⁶), 116.4 (C⁸), 116.2 (C⁷), 66.8 (C¹), 66.2 (C^1’), 66.1 (C⁴), 46.0 (C²), 42.4 (C¹¹), 42.6 (C^2’), 16.2 (C¹²); HRMS (ESl): calculated for C₂₀H₂₄N₂O₃Na [M+Na]⁺ requires m/z 363.1679, found m/z 363.1684; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO2:i-PrOH 90:10, 2.0 mL/min, 140 bar, 40 °C. Retention times: 32.3 mins (minor), 35.2 mins (major), e.r. = 96.5:3.5. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. N,N-Dimethyl-2-(phenylamino)-3-(p-tolyl)butanamide (4a): General procedure C: The reaction was carried out with substrate 1a (17.8 mg, 0.10 mmol, 100 mol%) and 1-methyl-4-vinylbenzene (26.0 µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 70:30) afforded the title compound (19.8 mg, 67%, >30:1 B:L, d.r. = 8:1 a:b, e.r. = 96.5:3.5) as a pale-yellow solid.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 8:1. m.p. = 121 – 123 °C (hexane/EtOAc); [^]^ ^^ = +15.1 (c = 0.14, CHCl₃); IR (thin film) ν_max/cm⁻¹: 3379 (br), 3009 (s), 2931 (s), 2855 (s), 1611 (s); 1H NMR (500 MHz, CDCl₃) Data for the major diastereomer a: δ 7.17 – 7.09 (m, 6H, H⁷ + H¹² + H¹³), 6.72 – 6.69 (m, 1H, H⁸), 6.63 (d, J = 8.0 Hz, 2H, H⁶), 4.69 – 4.31 (m, 2H, H³ + H⁴), 3.32 – 3.27 (m, 1H, H⁹), 2.90 (s, 3H, H¹), 2.67 (s, 3H, H^1’), 2.32 (s, 3H, H¹⁵), 1.35 (d, J = 7.0 Hz, 3H, H¹⁰). Characteristic signals for the minor diastereomer b: 6.55 (d, J = 8.0 Hz, 2H, H⁶), 2.75 (s, 3H, H¹), 2.62 (s, 3H, H^1’), 1.44 (d, J = 7.0 Hz, 3H, H¹⁰); 13C NMR (126 MHz, CDCl₃) Data for the major diastereomer a only: δ 171.7 (C²), 147.1 (C⁵), 139.5 (C¹¹), 136.6 (C¹⁴), 129.4 (C⁷), 129.3 (C¹³), 127.9 (C¹²), 118.1 (C⁸), 114.1 (C⁶), 58.5 (C³), 42.0 (C⁹), 37.1 (C¹), 35.8 (C^1’), 21.2 (C¹⁵), 16.2 (C⁹); HRMS (ESl): calculated for C19H25N2O [M+H]⁺ requires m/z 296.1961, found m/z 297.1962; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO2:i-PrOH 95:5, 2.5 mL/min, 140 bar, 40 °C. Retention times: 11.1 mins (major), 11.6 mins (minor), e.r. = 96.5:3.5. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-3-(4-Bromophenyl)-N,N-dimethyl-2-(phenylamino)butanamide (5a): reaction was carried out with substrate 1a (17.8 mg, 0.10 mmol, , 4-vinylbenzene (26.0 µL, 0.20 mmol, 200 mol%) at 140 ^oC. Purification of the residue by FCC (hexane/EtOAc 70:30) afforded the title compound (18.0 mg, 50%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 98:2) as a pale-yellow solid.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 8:1. m.p. = 102 – 104 °C (hexane/EtOAc); [^]^^ ^ = - 6.7 (c = 1.0 CHCl₃); IR (thin film) ν_max/cm⁻¹: 3328 (br), 2924 (s), 2852 (s), 1637 (s), 1602 (s), 1490 (s), 1398 (s), 750 (s), 693 (s); 1H NMR (500 MHz, CDCl3) Data for the major diastereomer a only: δ 7.42 (d, J = 8.5 Hz, 2H, H¹³), 7.16 – 7.11 (m, 4H, H⁷ + H¹²), 6.73 – 6.70 (m, 1H, H⁸), 6.62 (d, J = 8.5 Hz, 2H, H⁶), 4.69 – 4.10 (m, 2H, H³ + H⁴), 3.30 – 3.24 (m, 1H, H⁹), 2.91 (s, 3H, H¹), 2.77 (s, 3H, H^1’), 1.35 (d, J = 7.0 Hz, 3H, H¹⁰); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 171.4 (C²), 146.8 (C⁵), 141.4 (C¹¹), 131.4 (C¹³), 129.7 (C¹²), 129.3 (C⁷), 120.7 (C¹⁴), 118.4 (C⁸), 114.1 (C⁶), 58.2 (C³), 42.0 (C⁹), 37.1 (C^1’), 35.7 (C¹), 16.3 (C¹⁰); HRMS (ESl): calculated for C₁₈H₂₁BrN₂ONa [M+Na]⁺ requires m/z 383.0729, found m/z 383.0733; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO2:i-PrOH 90:10, 2.0 mL/min, 140 bar, 40 °C. Retention times: 9.2 mins (minor), 9.8 mins (major), e.r. = 98:2. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-3-([1,1'-Biphenyl]-4-yl)-N,N-dimethyl-2-(phenylamino)butanamide (6a): Ge action was carried out with substrate 1a (17.8 mg, 0.10 mmol, 10 phenyl (36.0 mg, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 70:30) afforded the title compound (34.4 mg, 96%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 97:3) as a pale-yellow solid.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 4:1. m.p. = 103 – 105 °C (hexane/EtOAc); [^]^ ^^ = -11.6 (c = 1.0 CHCl₃); IR (thin film) ν_max/cm⁻¹: 3330 (br), 3028 (s), 1638 (s), 1602 (s), 1499 (s), 1398 (s), 750 (s), 695 (s); 1H NMR (500 MHz, CDCl₃) Data for the major diastereomer a only: δ 7.60 – 7.54 (m, 4H, ArH), 7.46 – 7.43 (m, 2H, H¹⁷), 7.36 – 7.32 (m, 3H, ArH), 7.18 – 7.15 (m, 2H, H⁷), 6.73 – 6.70 (m, 1H, H⁸), 6.66 (d, J = 7.5 Hz, 2H, H⁶), 5.30 – 4.37 (m, 2H, H³ + H⁴), 3.41 – 3.36 (m, 1H, H⁹), 2.92 (s, 3H, H¹), 2.71 (s, 3H, H^1’), 1.41 (d, J = 7.0 Hz, 3H, H¹⁰); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 171.5 (C²), 146.8 (C⁵), 141.6 (C¹¹), 140.7 (C¹⁵), 139.8 (C¹⁴), 129.3 (C⁷), 128.7 (C¹⁷), 128.3 (C¹²), 127.2 (C¹⁸), 127.1 (C¹⁶), 127.0 (C¹³), 118.2 (C⁸), 114.1 (C⁶), 58.3 (C³), 42.0 (C⁹), 37.0 (C¹), 35.7 (C^1’), 16.0 (C¹⁰); HRMS (ESl): calculated for C24H26N2ONa [M+Na]⁺ requires m/z 381.1937, found m/z 381.1948; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO2:i-PrOH 90:10, 2.0 mL/min, 140 bar, 40 °C. Retention times: 19.7 mins (minor), 21.7 mins (major), e.r. = 97:3. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-3-(4-Methoxyphenyl)-N,N-dimethyl-2-(phenylamino)butanamide (7a): 10 O Me 1 General procedure C: The reaction was carried out with substrate 1a (17.8 mg, 0.10 mmol, 100 mol%) and 1-methoxy-4-vinylbenzene (27.0 µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 70:30) afforded the title compound (18.7 mg, 60%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 98:2) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 9:1. [^]^ ^^ = +2.9 (c = 0.26, CHCl₃); IR (thin film) ν_max/cm⁻¹: 3711 (s), 3681 (s), 3344 (br), 2966 (s), 2936 (s), 2873 (s), 2835 (s), 1636 (s), 1602 (s), 1583 (s), 1510 (s); 1H NMR (500 MHz, CDCl₃) Data for the major diastereomer a only: δ 7.17 – 7.14 (m, 4H, H⁷ + H¹²), 6.85 (d, J = 8.5 Hz, 2H, H¹³), 6.72 – 6.69 (m, 1H, H⁸), 6.64 (d, J = 7.5 Hz, 2H, H⁶), 4.67 – 4.29 (m, 2H, H³ + H⁴), 3.79 (s, 3H, H¹⁵), 3.32 – 3.26 (m, 1H, H⁹), 2.90 (s, 3H, H¹), 2.68 (s, 3H, H^1’), 1.35 (d, J = 7.0 Hz, 3H, H¹⁰); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 171.5 (C²), 158.5 (C¹⁴), 146.9 (C⁵), 134.4 (C¹¹), 129.3 (C⁷), 128.8 (C¹²), 118.0 (C⁸), 113.9 (C¹³), 113.8 (C⁶), 58.4 (C³), 55.2 (C¹⁵), 41.4 (C⁹), 36.9 (C¹), 35.6 (C^1’), 16.1 (C¹⁰); HRMS (ESl): calculated for C₁₉H₂₅N₂O₂ [M+H]⁺ requires m/z 313.1911, found m/z 313.1912; Chiral SFC: YMC Chiral ART Cellulose-SC column (25 cm), CO2:i-PrOH 85:15, 3.0 mL/min, 140 bar, 40 °C. Retention times: 5.6 mins (minor), 6.9 mins (major), e.r. = 98:2. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-3-(4-(Tert-butyl)phenyl)-N,N-dimethyl-2-(phenylamino)butanamide (8a): was carried out with substrate 1a (17.8 mg, 0.10 mmol, vinylbenzene (37.0 µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 70:30) afforded the title compound (19.6 mg, 58%, >30:1 B:L, d.r. = 8:1 a:b, e.r. = 97:3) as a pale-yellow solid.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 8:1. m.p. = 121 – 123 (hexane/EtOAc); [^]^ ^^ = -2.5 (c = 0.16, CHCl3); IR (thin film) νmax/cm⁻¹: 3681 (s), 3350 (br), 2960 (s), 2925 (s), 2868 (s), 1638 (s), 1632 (s), 1502 (s); 1H NMR (500 MHz, CDCl₃) Data for the major diastereomer a: δ 7.33 – 7.31 (m, 2H, H¹³), 7.18 – 7.13 (m, 4H, H⁷ + H¹²), 6.71 – 6.68 (m, 1H, H⁸), 6.62 (d, J = 7.5 Hz, 2H, H⁶), 4.80 – 4.29 (m, 2H, H³ + H⁴), 3.34 – 3.29 (m, 1H, H⁹), 2.89 (s, 3H, H¹), 2.61 – 2.60 (s, 3H, H^1’), 1.35 (d, J = 7.0 Hz, 3H, H¹⁰), 1.30 (s, 9H, H¹⁶). Characteristic signals for the minor diastereomer b: 6.49 (d, J = 7.5 Hz, 2H, H⁶), 2.74 (s, 3H, H¹), 1.45 (d, J = 7.0 Hz, 3H, H¹⁰); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 171.7 (C²), 150.0 (C¹⁴), 147.0 (C⁵), 139.5 (C¹¹), 129.4 (C⁷), 127.7 (C¹³), 125.4 (C¹²), 118.1 (C⁸), 114.1 (C⁶), 58.5 (C³), 41.9 (C⁹), 36.9 (C¹), 35.8 (C^1’), 34.6 (C¹⁵), 31.5 (C¹⁶), 15.9 (C¹⁰); HRMS (ESl): calculated for C₂₂H₃₁N₂O [M+H]⁺ requires m/z 339.2431, found m/z 339.2434; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO2:i-PrOH 95.5:4.5, 2.5 mL/min, 140 bar, 40 °C. Retention times: 11.5 mins (major), 14.1 mins (minor), e.r. = 97:3. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-3-(4-Fluorophenyl)-N,N-dimethyl-2-(phenylamino)butanamide (9a): 10 O Me 1 12 Me 3 11 N 2 9 13 Me 4 14 NH 5 F reaction was carried out with substrate 1a (17.8 mg, 0.10 mmol, vinylbenzene (24.0 µL, 0.20 mmol, 200 mol%). Purification of the 60:40) afforded the title compound (18.6 mg, 62%, >30:1 B:L, d.r. = 8:1 a:b, e.r. = 98.5:1.5) as a pale-yellow solid.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 8:1. m.p. = 117 – 120 °C (hexane/EtOAc); [^]^ ^^ = -5.1 (c = 0.19, CHCl3); IR (thin film) νmax/cm⁻¹: 3709 (s), 3681 (s), 3337 (br), 2968 (s), 2937 (s), 2873 (s), 2845 (s), 1637 (s), 1602 (s), 1508 (s); 1H NMR (500 MHz, CDCl₃) Data for the major diastereomer a: δ 7.22 – 7.13 (m, 4H, H¹² + H¹³), 7.01 – 6.97 (m, 2H, H⁷), 6.72 – 6.69 (m, 1H, H⁸), 6.61 (d, J = 8.0 Hz, 2H, H⁶), 4.73 – 4.29 (m, 2H, H³ + H⁴), 3.33 – 3.27 (m, 1H, H⁹), 2.90 (s, 3H, H¹), 2.76 – 2.75 (m, 3H, H^1’), 1.36 (d, J = 7.0 Hz, 3H, H¹⁰). Characteristic signals for the minor diastereomer b: 6.52 (d, J = 8.0 Hz, 2H, H⁶), 2.68 (s, 3H, H¹), 1.43 (d, J = 7.0 Hz, 3H, H¹⁰); 13C NMR (126 MHz, CDCl₃) Data for the major diastereomer a only: δ 171.7 (C²), 161.9 (d, J = 245.0 Hz, C¹⁴), 147.1 (C⁵), 138.2 (d, J = 3.0 Hz, C¹¹), 129.5 – 129.4 (C⁷ + C¹²), 118.4 (C⁸), 115.3 (d, J = 21.0 Hz, H¹³), 114.2 (C⁶), 58.5 (C³), 41.9 (C⁹), 37.1 (C¹), 35.8 (C^1’), 16.5 (C¹⁰); ¹⁹F NMR (471 MHz, CDCl3) δ -115.90; HRMS (ESl): calculated for C18H22FN2O [M+H]⁺ requires m/z 301.1711, found m/z 301.1712; Chiral SFC: DAICEL CHIRALCEL OD- H column (25 cm), CO2:i-PrOH 97:3, 2.5 mL/min, 140 bar, 40 °C. Retention times: 15.1 mins (minor), 16.2 mins (major), e.r. = 98.5:1.5. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-N,N-Dimethyl-2-(phenylamino)-3-(o-tolyl)butanamide (10a): General procedure C: The reaction was carried out with substrate 1a (17.8 mg, 0.10 mmol, 100 mol%) and 1-methyl-2-vinylbenzene (26.0 µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 60:40) afforded the title compound (21.9 mg, 74%, >30:1 B:L, d.r. = 13:1 a:b, e.r. = 98:2) as a pale-yellow solid.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 8:1. m.p. = 135 – 137 °C (hexane/EtOAc); [^]^ ^^ = +19.4 (c = 0.25, CHCl3); IR (thin film) νmax/cm⁻¹: 3681 (s), 3329 (br), 3052 (s), 3017 (s), 2967 (s), 2937 (s), 2873 (s), 2845 (s), 1635 (s), 1602 (s); 1H NMR (500 MHz, CDCl3) Data for the major diastereomer a: δ 7.21 – 7.10 (m, 6H, H⁷ + H¹⁴ + H¹⁵ + H¹⁶ + H¹⁷), 6.73 – 6.70 (m, 1H, H⁸), 6.65 (d, J = 7.5 Hz, 2H, H⁶), 4.76 – 4.38 (m, 2H, H³ + H⁴), 3.66 – 3.61 (m, 1H, H⁹), 2.86 (s, 3H, H¹), 2.56 (s, 3H, H^1’), 2.44 (s, 3H, H¹³), 1.34 (d, J = 7.0 Hz, 3H, H¹⁰). Characteristic signals for the minor diastereomer b: 2.71 (s, 2H, H¹), 2.62 (s, 2H, H^1’), 2.35 (s, 2H, H¹³), 1.41 (d, J = 7.0 Hz, 2H, H¹⁰); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 171.8 (C²), 147.0 (C⁵), 140.9 (C¹¹), 136.1 (C¹²), 130.5 (C¹⁴), 129.5 (C⁷), 126.7 (ArC), 126.6 (ArC), 126.2 (ArC), 118.3 (C⁸), 114.3 (C⁶), 56.5 (C³), 37.4 (C⁹), 36.8 (C¹), 35.7 (C^1’), 19.9 (C¹³), 15.9 (C¹⁰); HRMS (ESl): calculated for C₁₉H₂₅N₂O [M+H]⁺ requires m/z 297.1961, found m/z 297.1964; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO₂:i-PrOH 92:8, 2.0 mL/min, 140 bar, 40 °C. Retention times: 8.6 mins (major), 9.7 mins (minor), e.r. = 98:2. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-3-(2-Chlorophenyl)-N,N-dimethyl-2-(phenylamino)butanamide (11a): reaction was carried out with substrate 1a (17.8 mg, 0.10 mmol, 100 mol%) and 1-chloro-2-vinylbenzene (25.4 µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 70:30) afforded the title compound (11.7 mg, 37%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 98:2) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 7:1. [^]^ ^^ = +19.7 (c = 1.0 CHCl3); IR (thin film) νmax/cm⁻¹: 3344 (br), 2933 (s), 1639 (s), 1603 (s), 1504 (s), 752 (s), 693 (s); 1H NMR (500 MHz, CDCl₃) Data for the major diastereomer a only: δ 7.36 (d, J = 9.5 Hz, 1H, H¹³), 7.29 – 7.27 (m, 1H, H¹⁶), 7.24 – 7.15 (m, 4H, H⁷ + H¹⁴ + H¹⁵), 6.77 (d, J = 8.0 Hz, 2H, H⁶), 6.75 – 6.72 (m, 1H, H⁸), 5.24 – 4.50 (m, 2H, H³ + H⁴), 3.99 – 3.94 (m, 1H, H⁹), 2.80 (s, 3H, H¹), 2.55 (s, 3H, H^1’), 1.39 (d, J = 7.0 Hz, 3H, H¹⁰); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 170.8 (C²), 146.5 (C⁵), 139.6 (C¹¹), 134.2 (C¹²), 129.4 (ArC), 129.3 (C⁷), 128.8 (ArC), 128.0 (ArC), 126.8 (ArC), 118.2 (C⁸), 114.2 (C⁶), 55.2 (C³), 37.5 (C⁹), 36.6 (C¹), 35.4 (C^1’), 14.7 (C¹⁰); HRMS (ESl): calculated for C18H21ClN2ONa [M+Na]⁺ requires m/z 339.1235, found m/z 339.1250; Chiral SFC: YMC Chiral ART Cellulose-SB column (25 cm), CO2:i-PrOH 90:10, 2.0 mL/min, 140 bar, 40 °C. Retention times: 7.1 mins (major), 7.9 mins (minor), e.r. = 98:2. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-3-(2-Fluorophenyl)-N,N-dimethyl-2-(phenylamino)butanamide (12a): 10 O Me F 1 Me 3 11 12 N 2 9 13 Me 4 NH 16 14 reaction was carried out with substrate 1a (17.8 mg, 0.10 mmol, (24.0 µL, 0.20 mmol, 200 mol%). Purification of the residue by 70:30) afforded the title compound (23.1 mg, 77%, >30:1 B:L, d.r. = 6:1 a:b, e.r. = 98:2) as a pale-yellow solid.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 6:1. m.p. = 78 – 81 °C (hexane/EtOAc); [^]^ ^^ = -2.2 (c = 0.34, CHCl₃); IR (thin film) ν_max/cm⁻¹: 3681 (s), 3333 (br), 2973 (s), 2938 (s), 2874 (s), 2845 (s), 1638 (s), 1602 (s), 1584 (s); 1H NMR (500 MHz, CDCl₃) Data for the major diastereomer a: δ 7.27 – 7.00 (m, 6H, H⁷ + H¹³ + H¹⁴ + H¹⁵ + H¹⁶), 6.71 – 6.62 (m, 3H, H⁶ + H⁸), 4.87 – 4.38 (m, 2H, H³ + H⁴), 3.70 – 3.64 (m, 1H, H⁹), 2.88 (s, 3H, H¹), 2.76 (s, 3H, H^1’), 1.37 (d, J = 7.0 Hz, 3H, H¹⁰). Characteristic signals for the minor diastereomer b: 6.37 (d, J = 7.0 Hz, 3H, H⁶), 3.01 (s, 4H, H¹), 2.86 (s, 4H, H^1’); 13C NMR (126 MHz, CDCl₃) Data for the major diastereomer a only: δ 171.7 (C²), 161.3 (d, J = 244.0 Hz, C¹²), 147.1 (C⁵), 129.5 – 129.2 (m, ArC), 128.5 (d, J = 8.5 Hz, ArC), 124.3 (d, J = 3.5 Hz, C¹⁵), 118.2 (C⁸), 115.3 (d, J = 22.7 Hz, C¹³), 114.1 (C⁶), 56.6 (C³), 37.0 (C¹), 35.7 (C^1’), 35.6 (C⁹), 15.2 (C¹⁰); 19F NMR (471 MHz, CDCl3) δ -117.92 (dt, J = 12.0, 6.5 Hz), -118.48 (dt, J = 12.0, 6.5 Hz); HRMS (ESl): calculated for C18H22FN2O [M+H]⁺ requires m/z 301.1711, found m/z 301.1713; Chiral SFC: YMC Chiral ART Cellulose-SC column (25 cm), CO2:i-PrOH 90:10, 2.0 mL/min, 140 bar, 40 °C. Retention times: 7.7 mins (minor), 9.6 mins (major), e.r. = 98:2. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-3-(3-Chlorophenyl)-N,N-dimethyl-2-(phenylamino)butanamide (13a): General procedure C: The reaction was carried out with substrate 1a (17.8 mg, 0.10 mmol, 100 mol%) and 1-chloro-3-vinylbenzene (25.0 µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 70:30) afforded the title compound (13.3 mg, 42%, >30:1 B:L, d.r. = 9:1 a:b, e.r. = 97:3) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 9:1. [^]^ ^^ = -8.8 (c = 0.29, CHCl₃); IR (thin film) ν_max/cm⁻¹: 3668 (s), 3329 (br), 3055 (s), 3025 (s), 2968 (s), 2936 (s), 2877 (s), 1636 (s), 1601 (s), 1572 (s); 1H NMR (500 MHz, CDCl3) Data for the major diastereomer a: δ 7.24 – 7.10 (m, 6H, H⁷ + H¹² + H¹⁴ + H¹⁵ + H¹⁶), 6.73 – 6.70 (m, 1H, H⁸), 6.62 (d, J = 8.0 Hz, 2H, H⁶), 4.68 – 4.32 (m, 2H, H³ + H⁴), 3.32 – 3.26 (m, 1H, H⁹), 2.91 (s, 3H, H¹), 2.74 (s, 3H, H^1’), 1.35 (d, J = 7.0 Hz, 3H, H¹⁰). Characteristic signals for the minor diastereomer b: 6.54 (d, J = 8.0 Hz, 2H, H⁶), 2.76 (s, 3H, H¹), 2.68 (s, 3H, H^1’), 1.44 (d, J = 7.0 Hz, 3H, H¹⁰); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 171.5 (C²), 146.9 (C⁵), 144.8 (C¹¹), 134.4 (C¹³), 129.8 (ArC), 129.5 (C⁷), 128.1 (ArC), 127.2 (ArC), 126.4 (ArC), 118.5 (C⁸), 114.3 (C⁶), 58.2 (C³), 42.4 (C⁹), 37.2 (C¹), 35.8 (C^1’), 16.2 (C¹⁰); HRMS (ESl): calculated for C₁₈H₂₂ClN₂O [M+H]⁺ requires m/z 317.1415, found m/z 317.1416; Chiral SFC: YMC Chiral ART Cellulose-SC column (25 cm), CO₂:i-PrOH 90:10, 2.0 mL/min, 140 bar, 40 °C. Retention times: 9.4 mins (minor), 11.8 mins (major), e.r. = 97:3. (2S,3S)-N,N-Dimethyl-3-(perfluorophenyl)-2-(phenylamino)butanamide (14a): reaction was carried out with substrate 1a (17.8 mg, 0.10 mmol, 100 mol%) and 1,2,3,4,5-pentafluoro-6-vinylbenzene (27.0 µL, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 70:30) afforded the title compound (27.5 mg, 74%, >30:1 B:L, d.r. = 2:1 a:b, e.r. = 98.5:1.5) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 2:1. [^]^ ^^ = -95.3 (c = 0.13, CHCl3); IR (thin film) ν_max/cm⁻¹: 3323 (br), 3058 (s), 3031 (s), 2979 (s), 2940 (s), 2887 (s), 1643 (s), 1602 (s), 1521 (s); 1H NMR (500 MHz, CDCl₃) Data for diastereomers a and b: δ 7.18 – 7.15 (m, 0.8H, H^7b), δ 7.10 – 7.07 (m, 1.2H, H^7a), 6.75 – 6.72 (m, 0.4H, H^8b), 6.71 – 6.68 (m, 0.6H, H^8a), 6.65 (d, J = 8.0 Hz, 0.7H, H^6b), 6.54 (d, J = 8.0 Hz, 1.2H, H^6a), 4.83 – 4.79 (m, 1H, H³), 3.72 – 3.63 (m, 1H, H⁹), 3.18 (s, 1.8H, H^1a), 2.99 (s, 1.8H, H^1a’), 2.96 (s, 1H, H^1b), 2.80 (s, 1H, H^1b’), 1.46 (d, J = 7.0 Hz, 1.2H, H^10b), 1.34 (d, J = 7.0 Hz, 1.9H, H^10a); 13C NMR (126 MHz, CDCl₃) Data for diastereomers a and b: δ 172.6 (C^2a), 171.7 (C^2b), 147.2 (C⁵), 146.9 (C¹¹), 129.6 (C^7b), 129.5 (C^7a), 119.3 (C^8a), 118.7 (C^8b), 114.6 (C^6a), 113.7 (C^6b), 56.4 (C³), 37.7 (C^1a), 37.3 (C^1b), 36.0 (C^1a’), 35.9 (C^1b’), 35.1 (C^9a), 34.9 (C^9b), 15.8 (C^10b), 15.7 (C^10a); 19F NMR (471 MHz, CDCl3) Data for diastereomers a and b: δ -141.34 (dd, J = 22.5, 7.5 Hz, C¹²-F^b), -142.52 (dd, J = 22.5, 7.5 Hz, C¹²-F^b), -156.28 (t, J = 21.0 Hz, C¹⁴-F^b), -156.61 (t, J = 21.0 Hz, C¹⁴-F^a), - 161.85 (td, J = 22.5, 7.5 Hz, C¹³-F^b), -162.45 (td, J = 22.5, 7.5 Hz, C¹³-F^a); HRMS (ESl): calculated for C₁₈H₁₈F₅N₂O [M+H]⁺ requires m/z 373.1334, found m/z 373.1333; Chiral SFC: DAICEL CHIRALPAK IE column (25 cm) PrOH 98:2, 3.5 mL/min, 140 bar, 40 °C. Retention times: 15.0 mins (minor), 15.8 mins (major), e.r. = 98.5:1.5. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-N,N-Dimethyl-3-(1-(methyl-(λ1-oxidaneyl)-(p-tolyl)sulfinyl)-1H-indol-3-yl)-2- (phenylamino)butanamide (15a): reaction was carried out with substrate 1a (17.8 mg, 0.10 mmol, (λ¹-oxidaneyl)-(p-tolyl)sulfinyl)-3-vinyl-1H-indole (62.4 mg, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 60:40) afforded the title compound (40.4 mg, 85%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 98:2) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 5:1. [^]^ ^^ = -4.5 (c = 1.0 CHCl₃); IR (thin film) ν_max/cm⁻¹: 3330 (br), 3053 (s), 1637 (s), 1602 (s), 1497 (s), 1173 (s), 747 (s), 671 (s); 1H NMR (500 MHz, CDCl₃) Data for the major diastereomer a only: δ 8.02 (d, J = 8.0 Hz, 1H, ArH), 7.70 (d, J = 8.0 Hz, 2H, H²⁰), 7.59 (d, J = 8.0 Hz, 1H, ArH), 7.43 (s, 1H, H¹⁸), 7.36 – 7.27 (m, 2H, ArH), 7.20 – 7.16 (m, 4H, ArH), 6.76 – 6.74 (m, 1H, H⁸), 6.66 (d, J = 8.0 Hz, 2H, H⁶), 5.12 – 4.39 (m, 2H, H³ + H⁴), 3.61 – 3.56 (m, 1H, H⁹), 2.85 (s, 3H, H¹), 2.63 (s, 3H, H^1’), 2.34 (s, 3H, H²³), 1.45 (d, J = 7.0 Hz, 3H, H¹⁰); 13C NMR (126 MHz, CDCl₃) Data for the major diastereomer a only: δ 171.4 (C²), 146.7 (C⁵), 144.8 (ArC), 135.2 (ArC), 135.1 (ArC), 130.5 (ArC), 129.8 (ArC), 129.3 (ArC), 126.6 (C²⁰), 124.8 (ArC), 124.1 (ArC), 123.4 (ArC), 123.2 (ArC), 119.3 (ArC), 118.2 (C⁸), 113.93 (C⁶), 113.89 (ArC), 56.6 (C³), 37.1 (C¹), 35.6 (C^1’), 33.8 (C⁹), 21.5 (C²³), 16.1 (C¹⁰); HRMS (ESl): calculated for C + 27H29N3O3SNa [M+Na] requires m/z 498.1822, found m/z 498.1826; Chiral SFC: DAICEL CHIRALCEL IE column (25 cm), CO₂:i-PrOH 70:30, 3.0 mL/min, 180 bar, 40 °C. Retention times: 7.7 mins (minor), 8.8 mins (major), e.r. = 98:2. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-N,N-Dimethyl-3-(naphthalen-2-yl)-2-(phenylamino)butanamide (16a): General procedure C: The reaction was carried out with substrate 1a (17.8 mg, 0.10 mmol, 100 mol%) and 2-vinylnaphthalene (30.8 mg, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 70:30) afforded the title compound (21.9 mg, 66%, >30:1 B:L, d.r. = 7:1 a:b, e.r. = 98:2) as a pale-yellow solid.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 7:1. m.p. = 148 – 151 °C (hexane/EtOAc); [^]^ ^^ = -9.6 (c = 0.17, CHCl₃); IR (thin film) ν_max/cm⁻¹: 3334 (br), 3052 (s), 3017 (s), 2968 (s), 2932 (s), 2874 (s), 1636 (s), 1601 (s), 1504 (s); 1H NMR (500 MHz, CDCl₃) Data for the major diastereomer a: δ 7.82 – 7.79 (m, 3H, ArH), 7.70 (s, 1H, H¹²), 7.50 – 7.43 (m, 2H, ArH), 7.40 (d, J = 8.5 Hz, 1H, ArH), 7.17 – 7.14 (m, 2H, H⁷), 6.72 – 6.69 (m, 1H, H⁸), 6.66 (d, J = 8.0 Hz, 2H, H⁶), 4.82 – 4.45 (m, 2H, H³ + H⁴), 3.53 – 3.48 (m, 1H, H⁹), 2.89 (s, 3H, H¹), 2.62 (s, 3H, H^1’), 1.47 (d, J = 7.0 Hz, 3H, H¹⁰). Characteristic signals for the minor diastereomer b: 7.13 – 7.10 (m, 2H, H⁷), 6.59 (d, J = 8.0 Hz, 2H, H⁶), 2.69 (s, 3H, H¹), 2.55 (s, 3H, H^1’), 1.56 (d, J = 7.0 Hz, 3H, H¹⁰); 13C NMR (126 MHz, CDCl₃) Data for the major diastereomer a only: δ 171.7 (C²), 147.1 (C⁵), 140.2 (C¹¹), 133.6 (ArC), 132.7 (ArC), 129.5 (C⁷), 128.2 (ArC), 127.81 (ArC), 127.78 (ArC), 126.6 (ArC), 126.30 (ArC), 126.27 (ArC), 125.8 (ArC), 118.2 (C⁸), 114.1 (C⁶), 58.3 (C³), 42.6 (C⁹), 37.2 (C¹), 35.8 (C^1’), 16.2 (C¹⁰); HRMS (ESl): calculated for C22H25N2O [M+H]⁺ requires m/z 333.1961, found m/z 333.1962; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO₂:i-PrOH 85:15, 2.0 mL/min, 160 bar, 40 °C. Retention times: 7.9 mins (major), 9.5 mins (minor), e.r. = 98:2. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. Compound (17a): The reaction was carried out with substrate 1a (17.8 mg, 0.10 mmol, 100 mol%) and vinylferrocene (42.4 mg, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 70:30) afforded the title compound (38.2 mg, 98%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 98:2) as a yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 5:1. [^]^ ^^ = +126.0 (c = 1.0 CHCl₃); IR (thin film) ν_max/cm⁻¹: 3335 (br), 3054 (s), 1638 (s), 1602 (s), 1505 (s), 1106 (s), 749 (s); 1H NMR (500 MHz, CDCl3) Data for the major diastereomer a only: δ 7.18 – 7.15 (m, 2H, H⁷), 6.71 – 6.68 (m, 1H, H⁸), 6.59 (d, J = 8.0 Hz, 2H, H⁶), 4.77 (br s, 1H, H⁴), 4.36 (d, J = 4.0 Hz, 1H, H³), 4.18 – 4.09 (m, 9H, H¹² + H¹³ + H¹⁴ + H¹⁵ + H¹⁶ + H¹⁷ + H¹⁸ + H¹⁹ + H²⁰), 3.07 – 3.02 (m, 1H, H⁹), 2.86 (s, 3H, H¹), 2.60 (s, 3H, H^1’), 1.37 (d, J = 6.5 Hz, 3H, H¹⁰); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 171.2 (C²), 146.8 (C⁵), 129.3 (C⁷), (C⁸), 113.5 (C⁶), 69.1 – 66.4 (m, ArC), 58.3 (C³), 37.5 (C¹), 36.4 (C⁹), 35.6 (C^1’), 15.2 (C¹⁰); HRMS (ESl): calculated for C22H26FeN2ONa [M+Na]⁺ requires m/z 413.1287, found m/z 413.1291; Chiral SFC: YMC Chiral ART Cellulose- SC column (25 cm), CO₂:i-PrOH 80:20, 3.0 mL/min, 170 bar, 40 °C. Retention times: 7.7 mins (minor), 9.3 mins (major), e.r. = 98:2. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. ((2S,3S)-2-((4-Hydroxyphenyl)amino)-N,N-dimethyl-3-(1-(methyl-( λ1-oxidaneyl)-(p- tolyl)sulfinyl)-1H-indol-3-yl)butanamide (18a): was carried out with substrate 1a (19.4 mg, 0.10 mmol, oxidaneyl)-(p-tolyl)sulfinyl)-3-vinyl-1H-indole (62.4 mg, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 35:65) afforded the title compound (46.2 mg, 94%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 95.5:4.5) as a pale-yellow solid. ¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 5:1. m.p. = 96 – 98 °C (hexane/EtOAc); [^]^ ^^ = +2.8 (c = 1.0 CHCl₃); IR (thin film) ν_max/cm⁻¹: 3348 (br), 3053 (s), 1628 (s), 1515 (s), 1447 (s), 1173 (s), 1125 (s), 747 (s), 671 (s); 1H NMR (500 MHz, CDCl3) Data for the major diastereomer a only: δ 7.98 (d, J = 8.0 Hz, 1H, ArH), 7.68 (d, J = 8.0 Hz, 2H, H²¹), 7.52 (d, J = 8.0 Hz, 1H, ArH), 7.40 (s, 1H, H¹⁹), 7.32 – 7.28 (m, 1H, ArH), 7.25 – 7.22 (m, 1H, ArH), 7.14 (d, J = 8.0 Hz, 2H, H²²), 6.60 (d, J = 8.0 Hz, 2H, H⁷ ), 6.47 (d, J = 8.0 Hz, 2H, H⁶), 6.00 (br s, 1H, H⁹), 4.52 (d, J = 6.0 Hz, 1H, H³), 4.15 (br s, 1H, H⁴), 3.51 – 3.46 (m, 1H, H¹⁰), 2.81 (s, 3H, H¹), 2.63 (s, 3H, H^1’), 2.29 (s, 3H, H²⁴), 1.41 (d, J = 7.0 Hz, 3H, H¹¹); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 172.3 (C²), 149.1 (C⁸), 144.9 (C⁵), 140.5 (ArC), 135.17 (ArC), 135.16 (ArC), 130.5 (ArC), 129.8 (C²²), 126.6 (C²¹), 124.8 (ArC), 124.3 (ArC), 123.4 (ArC), 123.2 (ArC), 119.4 (ArC), 116.4 (C⁷), 116.2 (C⁶), 113.9 (C¹²), 58.8 (C³), 37.1 (C¹), 35.8 (C^1’), 33.9 (C¹⁰), 21.5 (C²⁴), 16.3 (C¹¹); HRMS (ESl): calculated for C27H30N3O4S [M+H]⁺ requires m/z 492.1952, found m/z 492.1966; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO2:i-PrOH 80:20, 2.0 mL/min, 170 bar, 40 °C. Retention times: 13.9 mins (major), 16.3 mins (minor), e.r. = 95.5:4.5. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2S,3S)-3-(3-Chlorophenyl)-2-((4-hydroxyphenyl)amino)-1-morpholinobutan-1-one (13n): Ge reaction was carried out with substrate 1n (23.6 mg, 0.10 mmol, 10 inylbenzene (25.0 µL, 0.20 mmol, 200 mol%). Purification of the resdue by CC ( exane/ tOAc 35:65) afforded the title compound (29.9 mg, 80%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 97:3) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 5:1. [^]^^ ^ = -9.8 (c = 1.0 CHCl₃); IR (thin film) ν_max/cm⁻¹: 3327 (br), 2968 (s), 1624 (s), 1515 (s), 1432 (s), 1224 (s), 1114 (s), 1033 (s), 827 (s), 783 (s); 1H NMR (500 MHz, CDCl3) Data for the major diastereomer a only: δ 7.24 – 7.21 (m, 3H, H¹⁴ + H¹⁶ + H¹⁷), 7.14 – 7.12 (m, 1H, H¹⁸), 6.63 (d, J = 8.0 Hz, 2H, H⁸), 6.53 (d, J = 8.0 Hz, 2H, H⁷), 5.93 (br s, 1H, H¹⁰), 4.68 – 3.99 (m, 2H, H⁴ + H⁵), 3.63 – 3.52 (m, 4H, H¹ + H²), 3.40 – 3.13 (m, 5H, H^1’ + H^2’ + H¹¹), 1.35 (d, J = 7.0 Hz, 3H, H¹²); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 170.7 (C³), 149.6 (C⁹), 144.5 (C⁶), 139.7 (C¹³), 134.4 (C¹⁵), 129.8 (ArC), 127.9 (ArC), 127.2 (ArC), 126.2 (C¹⁸), 117.0 (C⁸), 116.3 (C⁷), 66.7 (C¹), 66.2 (C^1’), 60.2 (C⁴), 46.2 (C²), 42.5 (C^2’), 42.1 (C¹¹), 16.5 (C¹²); HRMS (ESl): calculated for C₂₀H₂₄ClN₂O₃ [M+H]+ requires m/z 375.1470, found m/z 375.1479; Chiral SFC: YMC Chiral ART Cellulose-SC column (25 cm), CO₂:i-PrOH 80:20, 2.0 mL/min, 170 bar, 40 °C. Retention times: 7.5 mins (minor), 7.9 mins (major), e.r. = 97:3. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (S)-N,N,3-Trimethyl-3-phenyl-2-(phenylamino)butanamide (19a): General procedure C: The reaction was carried out with substrate 1a (17.8 mg, 0.10 mmol, 100 mol%) and prop-1-en-2-ylbenzene (52.0 µL, 0.40 mmol, 400 mol%) and was run for 96 hours at 140 ^oC. Purification of the residue by FCC (hexane/EtOAc 65:35) afforded the title compound (6.2 mg, 21%, >30:1 B:L, e.r. = 95:5) as a pale-yellow solid.¹H NMR analysis of the crude material gave >30:1 B:L. m.p. = 121 – 123 °C (hexane/EtOAc). [^]^ ^^ = -15.8 (c = 1.0, CHCl₃); IR (thin film) ν_max/cm⁻¹: 3335 (br), 2933 (s), 1636 (s), 1601 (s), 1498 (s), 750 (s), 694 (s); 1H NMR (500 MHz, CDCl₃) δ 7.47 (d, J = 10.0 Hz, 2H, H¹²), 7.34 – 7.30 (m, 2H, H¹³), 7.25 – 7.22 (m, 1H, H¹⁴), 7.16 – 7.12 (m, 2H, H⁷), 6.73 – 6.70 (m, 1H, H⁸), 6.65 (d, J = 7.5 Hz, 2H, H⁶), 4.81 (br s, 1H, H⁴), 4.35 (s, 1H, 2.68 (s, 3H, H¹), 2.26 (s, 3H, H^1’), 1.59 (s, 3H, H¹⁰), 1.52 (s, 3H, H^10’); 13C NMR (126 MHz, CDCl3) δ 172.0 (C²), 147.9 (C⁵), 146.1 (C¹¹), 129.3 (C⁷), 128.0 (C¹³), 126.9 (C¹²), 126.6 (C¹⁴), 118.3 (C⁸), 114.2 (C⁶), 61.6 (C³), 42.7 (C⁹), 36.8 (C¹), 35.2 (C^1’), 26.3 (C¹⁰), 22.8 (C^10’); HRMS (ESl): calculated for C₁₉H₂₅N₂O [M+H]⁺ requires m/z 297.1961, found m/z 297.1959; Chiral SFC: YMC Chiral ART Cellulose-SC column (25 cm), CO2:i-PrOH 90:10, 2.0 mL/min, 145 bar, 40 °C. Retention times: 5.4 mins (major), 7.8 mins (minor), e.r. = 95:5. (2R,3R)-N,N-Dimethyl-3-phenyl-2-(phenylamino)butanamide (3a’): The reaction was carried out with substrate 1a (17.8 mg, 0.10 mmol, µL, 0.20 mmol, 200 mol%) and (S)-SEGPHOS (3.05 mg, 5.00 μmol, 5 mol%). Purification of the residue by FCC (hexane/EtOAc 70:30) afforded the title compound (25.4 mg, 90%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 2.5:97.5) as a pale-yellow solid. ¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 9:1. m.p. = 101 – 103 °C (hexane/EtOAc); [^]^ ^^ = +8.8 (c = 1.0 CHCl3); Chiral SFC: YMC Chiral ART Cellulose-SC column (25 cm), CO₂:i-PrOH 80:20, 2.0 mL/min, 170 bar, 40 °C. Retention times: 4.9 mins (major), 5.9 mins (minor), e.r. = 2.5:97.5. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (4S,5S)-2,2,5-Trimethyl-4-(phenylamino)nonan-3-one (20s): General procedure C: The reaction was carried out with substrate 1s (19.1 mg, 0.10 mmol, 100 mol%), hex-1-ene (125 µL, 1.00 mmol, 1000 mol%), Ir(cod)2BARF (12.7 mg, 0.01 mmol, 10 mol%) and (R)-DM-SEGPHOS (7.23 mg, 0.01 mmol, 10 mol%) and was run in mesitylene (0.2 mL) at 110 °C. Purification of the residue by FCC (hexane/EtOAc 90:10) afforded the title compound (20.6 mg, 75%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 94:6) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 5:1. [^]^ ^^ = +9.9 (c = 1.0 CHCl₃); IR (thin film) νmax/cm⁻¹: 3381 (br), 2960 (s), 2929 (s), 1699 (s), 1601 (s), 1513 (s), 1497 (s), 745 (s), 690 (s); 1H NMR (500 MHz, CDCl₃) Data for the major diastereomer a only: δ 7.16 – 7.12 (m, 2H, H⁸), 6.71 – 6.68 (s, 1H, H⁹), 6.63 (d, J = 7.5 Hz, 2H, H⁷), 4.53 – 3.93 (m, 2H, H⁴ + H⁵), 1.96 – 1.88 (m, 1H, H¹⁰), 1.42 – 1.26 (m, 6H, H¹² + H¹³ + H¹⁴), 1.14 (s, 9H, H¹), 0.91 (t, J = 7.0 Hz, 3H, H¹⁵), 0.86 (d, J = 7.0 Hz, 3H, H¹¹); 13C NMR (126 MHz, CDCl₃) Data for the major diastereomer a only: δ 216.2 (C³), 148.0 (C⁶), 129.3 (C⁸), 118.0 (C⁹), 114.2 (C⁷), 60.9 (C⁴), 43.4 (C²), 35.4 (C¹⁰), 34.4 (C¹²), 29.7 (C¹³), 26.8 (C¹), 22.8 (C¹⁴), 14.1 (C¹¹), 13.9 (C¹⁵); HRMS (ESl): calculated for C18H30NO [M+H]⁺ requires m/z 276.2322, found m/z 276.2334; Chiral SFC: YMC Chiral ART Cellulose-SC column (25 cm), CO2:i-PrOH 97:3, 1.0 mL/min, 140 bar, 40 °C. Retention times: 6.1 mins (major), 6.5 mins (minor), e.r. = 94:6. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (4S,5S)-2,2,5,7-Tetramethyl-4-(phenylamino)octan-3-one (21s): The reaction was carried out with substrate 1s (19.1 mg, 0.10 mmol, , 1-ene (127 µL, 1.00 mmol, 1000 mol%), Ir(cod)₂BARF (12.7 mg, 0.01 mmol, 10 mol%) and (R)-DM-SEGPHOS (7.23 mg, 0.01 mmol, 10 mol%) and was run in mesitylene (0.2 mL) at 110 °C. Purification of the residue by FCC (hexane/EtOAc 90:10) afforded the title compound (18.7 mg, 68%, >30:1 B:L, d.r. = 2:1 a:b, e.r. = 90:10 as a pale- yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 2:1. [^]^ ^^ = +1.5 (c = 1.0 CHCl3); IR (thin film) νmax/cm⁻¹: 3380 (br), 2958 (s), 2971 (s), 1699 (s), 1601 (s), 1498 (s), 747 (s), 691 (s); 1H NMR (500 MHz, CDCl3) Data for diastereomers a and b: δ 7.16 – 7.12 (m, 2H, H⁸), 6.71 – 6.68 (m, 1H, H⁹), 6.62 (d, J = 7.5 Hz, 2H, H⁷), 4.42 – 4.30 (m, 1H, H⁴), 4.18 – 4.07 (m, 1H, H⁵), 2.05 – 1.97 (m, 1H, H¹⁰), 1.75 – 1.66 (m, 1H, H¹³), 1.28 – 1.25 (m, 2H, H¹²), 1.14 – 1.13 (m, 9H, H¹), 0.99 (d, J = 6.5 Hz, 1H, H^14b), 0.94 (d, J = 6.5 Hz, 2H, H^14a), 0.89 (d, J = 6.5 Hz, 3H, H¹¹), 0.84 (d, J = 6.5 Hz, 2H, H^14a’), 0.80 (d, J = 6.5 Hz, 1H, H^14b’); 13C NMR (126 MHz, CDCl₃) Data for diastereomers a and b: δ 216.2 (C^3b), 216.1 (C^3a), 148.1 (C^6a), 147.9 (C^6b), 129.3 (C⁸), 118.0 (C^9a), 117.8 (C^9b), 114.1 (C^7a), 113.8 (C^7b), 62.3 (C^4b), 61.4 (C^4a), 44.3 (C^2a), 43.3 (C^2b), 39.8 (C¹⁰), 33.6 (C^13b), 33.0 (C^13a), 26.73 (C^1a), 26.66 (C^1b), 25.24 (C^12a), 25.17 (C^12b), 24.3 (C^14b), 23.5 (C^14a), 21.9 (C^14a’), 21.1 (C^14b’), 17.5 (C^11b), 13.7 (C^11a); HRMS (ESl): calculated for C₁₈H₃₀NO [M+H]⁺ requires m/z 276.2322, found m/z 276.2331; Chiral SFC: YMC Chiral ART Cellulose-SC column (25 cm), CO₂:i-PrOH 97:3, 1.0 mL/min, 140 bar, 40 °C. Retention times: 5.8 mins (major), 6.1 mins (minor), e.r. = 90:10. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (4S,5S)-2,2,5,6-Tetramethyl-4-(phenylamino)heptan-3-one (22s): The reaction was carried out with substrate 1s (19.1 mg, 0.10 mmol, 1-ene (129 µL, 1.00 mmol, 1000 mol%), Ir(cod)2BARF (12.7 mg, 0.01 -DM-SEGPHOS (7.23 mg, 0.01 mmol, 10 mol%) and was run in mesitylene (0.2 mL) at 110 °C. Purification of the residue by FCC (hexane/EtOAc 90:10) afforded the title compound (11.8 mg, 45%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 71:29) as a pale- yellow oil. ¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 16:1. [^]^^ ^ = +20.6 (c = 1.0 CHCl3); IR (thin film) νmax/cm⁻¹: 3374 (br), 2958 (s), 1699 (s), 1602 (s), 1498 (s), 749 (s), 566 (s); 1H NMR (500 MHz, CDCl₃) Data for the major diastereomer a only: δ 7.16 – 7.12 (m, 2H, H⁸), 6.71 – 6.68 (m, 1H, H⁹), 6.62 (d, J = 7.5 Hz, 2H, H⁷), 4.66 (d, J = 3.0 Hz, 1H, H⁴), 4.09 (br s, 1H, H⁵), 1.75 – 1.64 (m, 2H, H¹⁰ + H¹²), 1.15 (s, 9H, H¹), 1.07 (d, J = 6.0 Hz, 3H, H¹³), 0.95 (d, J = 6.0 Hz, 3H, H^13’), 0.84 (d, J = 6.5 Hz, 3H, H¹¹); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 216.4 (C³), 147.9 (C⁶), 129.3 (C⁸), 118.1 (C⁹), 114.1 (C⁷), 59.3 (C⁴), 43.4 (C²), 41.0 (C¹⁰), 30.7 (C¹²), 26.9 (C¹), 21.7 (C¹³), 19.5 (C^13’), 10.2 (C¹¹); HRMS (ESl): calculated for C₁₇H₂₈NO [M+H]⁺ requires m/z 262.2165, found m/z 262.2181; Chiral SFC: DAICEL CHIRALCEL IE column (25 cm), CO2:i-PrOH 97:3, 1.0 mL/min, 140 bar, 40 °C. Retention times: 9.5 mins (major), 10.3 mins (minor), e.r. = 71:29. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (4S,5S)-9-((Tert-butyldimethylsilyl)oxy)-2,2,5-trimethyl-4-(phenylamino)nonan-3-one : General procedure C: The reaction was carried out with substrate 1s (19.1 mg, 0.10 mmol, 100 mol%), tert-butyl(hex-5-en-1-yloxy)dimethylsilane (42.8 mg, 1.00 mmol, 1000 mol%), Ir(cod)2BARF (12.7 mg, 0.01 mmol, 10 mol%) and (R)-DM-SEGPHOS (7.23 mg, 0.01 mmol, 10 mol%) and was run in mesitylene (0.2 mL) at 110 °C. Purification of the residue by FCC (hexane/EtOAc 97:3) afforded the title compound (16.2 mg, 40%, >30:1 B:L, d.r. = 5:1 a:b, e.r. = 96:4) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 5:1. [^]^ ^^ = +19.7 (c = 1.0 CHCl3); IR (thin film) νmax/cm⁻¹: 3381 (br), 2930 (s), 2857 (s), 1701 (s), 1601 (s), 1498 (s), 1251 (s), 1097 (s), 835 (s), 775 (s), 747 (s); 1H NMR (500 MHz, CDCl3) Data for diastereomers a and b: δ 7.15 – 7.12 (m, 2H, H⁸), 6.71 – 6.67 (m, 1H, H⁹), 6.64 – 6.61 (m, 2H, H⁷), 4.60 – 4.12 (m, 2H, H⁴ + H⁵), 3.63 – 3.55 (m, 2H, H¹⁵), 1.94 – 1.88 (m, 1H, H¹⁰), 1.56 – 1.25 (m, 6H, H¹² + H¹³ + H¹⁴), 1.14 – 1.12 (m, 9H, H¹), 0.90 – 0.86 (m, 12H, H¹¹ + H¹⁷), 0.05 – 0.03 (m, 6H, H¹⁶); 13C NMR (126 MHz, CDCl₃) Data for the major diastereomer a only: δ 216.1 (C³), 148.0 (C⁶), 129.3 (C⁸), 118.1 (C⁹), 114.2 (C⁷), 63.1 (C¹⁵), 60.9 (C⁴), 43.4 (C²), 35.5 (C¹⁰), 34.5 (C¹⁴), 32.9 (C¹²), 26.8 (C¹⁷), 26.0 (C¹), 23.9 (C¹³), 18.4 (C¹⁸), 13.9 (C¹¹), -5.3 (C¹⁶); HRMS (ESl): calculated for C24H43NO2SiNa [M+Na]⁺ requires m/z 428.2955, found m/z 428.2947; Chiral SFC: YMC Chiral ART Cellulose-SC column (25 cm), CO₂:i-PrOH 97:3, 0.5 mL/min, 140 bar, 40 °C. Retention times: 13.6 mins (major), 14.4 mins (minor), e.r. = 96:4. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (2R,3R)-N,N-Dimethyl-3-phenyl-2-((phenylamino)methyl)butanamide (homologated system): The reaction was carried out with substrate 1p (19.2 mg, 0.10 mmol, 100 mol%) and styrene (35.4 µL, 0.30 mmol, 300 mol%), Ir(cod)₂BARF (12.7 mg, 0.01 mmol, 10 mol%) and (R)-BINAP (6.23 mg, 0.01 mmol, 10 mol%) and was run for 96 hours at 140 ^oC. Purification of the residue by FCC (hexane/EtOAc 50:50) afforded the title compound (16.3 mg, 55%, >30:1 B:L, d.r. >20:1 a:b, e.r. = 71:29) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 2:1. [^]^ ^^ = -16.3 (c = 1.0 CHCl₃); IR (thin film) ν_max/cm⁻¹: 3348 (br), 2923 (s), 2854 (s), 1628 (s), 1602 (s), 1496 (s), 750 (s), 670 (s); 1H NMR (500 MHz, CDCl₃) Data for the major diastereomer a only: δ 7.37 – 7.33 (m, 2H, H¹⁴), 7.27 – 7.25 (m, 3H, H¹³ + H¹⁵), 7.10 – 7.06 (m, 2H, H⁸), 6.64 – 6.61 (m, 1H H⁹), 6.33 (d, J = 8.0 Hz, 2H, H⁷), 3.97 (br s, 1H, H⁵), 3.34 – 3.30 (m, 1H, H³), 3.26 – 3.22 (m, 1H, H⁴), 3.13 – 3.07 (m, 1H, H¹⁰), 3.00 – 2.96 (m, 4H, H¹ + H^4’), 2.86 (s, 3H, H^1’), 1.22 (d, J = 7.0 Hz, 3H, H¹¹); 13C NMR (126 MHz, CDCl3) Data for the major diastereomer a only: δ 174.5 (C²), 147.7 (C⁶), 144.5 (C¹²), 129.2 (C⁸), 128.7 (C¹⁴), 127.4 (C¹³), 126.8 (C¹⁵), 117.2 (C⁹), 112.7 (C⁷), 46.7 (C³), 45.3 (C⁴), 41.5 (C¹⁰), 37.7 (C¹), 35.8 (C^1’), 20.2 (C¹¹); HRMS (ESl): calculated for C19H25N2O [M+H]⁺ requires m/z 297.1961, found m/z 297.1968; Chiral SFC: DAICEL CHIRALCEL OD- H column (25 cm), CO₂:i-PrOH 80:20, 2.0 mL/min, 170 bar, 40 °C. Retention times: 3.6 mins (minor), 4.9 mins (major), e.r. = 71:29. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. (S)-2-((4-Hydroxyphenyl)amino)-3-methyl-1-(pyrrolidin-1-yl)-3-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)butan-1-one (25t): A with substrate 2-((4-hydroxyphenyl)amino)-1-(pyrrolidine-1- yl) mmol, 100 mol%), [Ir(cod)₂]BARF (9.54 mg, 7.50 μmol, 7.5 mol%), (R)-DM-SEGPHOS (5.42 mg, 7.50 μmol, 7.5 mol%). The Schlenk tube was evacuated and refilled with N₂ (three cycles), then 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2- dioxaborolane (75.0 µL, 0.40 mmol, 400 mol%) was added followed by anhydrous t-BuOH (0.1 mL, 1.0 M). The tube was sealed and heated at 110 °C for 96 hours. After cooling to r.t., the solvent was removed under reduced pressure and the crude reaction mixture was purified by FCC (hexane/EtOAc 50:50) affording the title compound (26.0 mg, 67%, >30:1 B:L, e.r. = 93:7) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L. [^]^ ^^ = - 32.7 (c = 1.0, CHCl3); IR (thin film) νmax/cm⁻¹: 2917 (s), 2849 (s), 1602 (s), 1508 (s), 1462 (s), 1364 (s), 1228 (s), 730 (s), 7008 (s); 1H NMR (500 MHz, CDCl₃) δ 6.68 (d, J = 8.5 Hz, 2H, H¹⁷ + H¹⁹), 6.53 (d, J = 8.0 Hz, 2H, H¹⁶ + H²⁰), 4.47 (br. s, 1H, H³), 3.97 (s, 1H, H⁸), 3.59 – 3.39 (m, 4H, H²² + H²⁵), 1.89 – 1.75 (m, 4H, H²³ + H²⁴), 1.28 (s, 12H, H^30-33), 1.01 (s, 3H, H²), 0.96 (s, 3H, H⁹); 13C NMR (126 MHz, CDCl3) δ 174.6 (C⁷), 148.8 (C¹⁵), 141.4 (C¹⁸), 116.3 (C¹⁷ + C¹⁹), 115.4 (C¹⁶ + C²⁰), 83.0 (C²⁷), 82.0 (C²⁸), 75.1 (C⁵), 66.2 (C⁸), 47.3 (C²²), 46.8 (C²⁵), 26.1 (C³⁰), 25.0 (C²³), 24.9 (C²⁴), 24.6 (C³¹), 24.0 (C³²), 22.9 (C²), 21.3 (C⁹); HRMS (ESl): calculated for C₂₁H₃₄BN₂O₄ [M+H]⁺ requires m/z 389.2606, found m/z 389.2615; Chiral SFC: YMC Chiral ART Cellulose-SC column (25 cm, CO₂:i-PrOH 75:25, 3.0 mL/min, 228 bar, rt. Retention times: 2.1 mins (minor), 2.5 mins (major), e.r. = 93:7. The racemic product was also obtained using the above procedure (rac-BINAP was used in place of (R)-DM-SEGPHOS) and purified by FCC. Applications and derivatizations 4-((2S,3S)-4-(Dimethylamino)-4-oxo-3-(phenylamino)butan-2-yl)benzyl 2-(1-(4- chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetate (24a): carried out with substrate 1a (17.8 mg, 0.10 mmol, (4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3- yl)acetate (94.6 mg, 0.20 mmol, 200 mol%). Purification of the residue by FCC (hexane/EtOAc 60:40) afforded the title compound (41.0 mg, 63%, >30:1 B:L, d.r. = 20:1 a:b, e.r. = 98:2) as a pale-yellow oil.¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 10:1. [^]^ ^^ = -4.0 (c = 1.0 CHCl₃); IR (thin film) ν_max/cm⁻¹: 3342 (br), 2931 (s), 1736 (s), 1681 (s), 1640 (s), 1602 (s), 1478 (s), 1316 (s), 1262 (s), 1160 (s), 754 (s), 735 (s); 1H NMR (500 MHz, CDCl₃) Data for the major diastereomer a only: δ 7.68 (d, J = 8.5 Hz, 2H, H³⁰), 7.49 (d, J = 8.5 Hz, 2H, H³¹), 7.30 – 7.23 (m, 4H, ArH), 7.18 – 7.15 (m, 2H, H⁷), 6.96 (d, J = 2.5 Hz, 1H, H²⁰), 6.90 (d, J = 9.0 Hz, 1H, ArH), 6.75 – 6.63 (m, 4H, ArH), 5.14 (s, 2H, H¹⁵), 4.70 – 4.34 (m, 2H, H³ + H⁴), 3.80 (s, 3H, H²²), 3.73 (s, 2H, H¹⁷), 3.36 – 3.30 (m, 1H, H⁹), 2.91 (s, 3H, H¹), 2.73 (s, 3H, H^1’), 2.40 (s, 3H, H²⁷), 1.39 (d, J = 7.0 Hz, 3H, H¹⁰); 13C NMR (126 MHz, CDCl₃) Data for the major diastereomer a only: δ 171.5 (C²), 170.6 (C¹⁶), 168.3 (C²⁸), 156.0 (C²¹), 146.9 (C⁵), 142.7 (C¹¹), 139.3 (ArC), 136.0 (ArC), 134.3 (ArC), 133.8 (ArC), 131.2 (C³⁰), 130.8 (C²⁰), 130.6 (ArC), 129.3 (C⁷), 129.1 (C³¹), 128.2 (C¹³), 128.1 (C¹²), 118.3 (C⁸), 114.9 (ArC), 114.1 (C⁶), 112.4 (ArC), 111.7 (ArC), 101.3 (C²⁰), 66.5 (C¹⁵), 58.3 (C³), 55.6 (C²²), 42.2 (C⁹), 36.9 (C¹), 35.6 (C^1’), 30.4 (C¹⁷), 16.3 (C¹⁰), 13.4 (C²⁷); HRMS (ESl): calculated for C38H39ClN3O5 [M+H]⁺ requires m/z 652.2573, found m/z 652.2592; Chiral SFC: DAICEL CHIRALCEL IE column (25 cm), CO₂:i-PrOH 70:30, 4.0 mL/min, 180 bar, 40 °C. Retention times: 21.5 mins (minor), 23.5 mins (major), e.r. = 98:2. To facilitate analysis by SFC, the major diastereoisomer was separated from the minor diastereoisomer by FCC. Synthesis of 3a on 1.00 mmol scale: A Schlenk tube was charged with amide 1a (178 mg, 1.00 mmol, 100 mol%), [Ir(cod)2]BARF (63.6 mg, 0.05 mmol, 5 mol%) and (R)-SEGPHOS (30.5 mg, 0.05 mmol, 5 mol%). The Schlenk tube was evacuated and refilled with N₂ (three cycles), then styrene (229 µL, 2.00 mmol, 200 mol%) was added followed by 1,4-dioxane (2.0 mL). The tube was sealed and heated at 130 °C for 72 hours. After cooling to r.t., the solvent was removed under reduced pressure and the crude reaction mixture was purified by FCC (hexane/EtOAc 65:35) to afford the desired product (265 mg, 94%, >30:1 B:L, d.r. = 10:1, e.r. = 98:2) as a pale-yellow solid. ¹H NMR analysis of the crude material gave >30:1 B:L and d.r. = 10:1. (2S,3S)-3-Phenyl-2-(phenylamino)butan-1-ol (50): mg, was to a solution of 3f (32.4 mg, 0.10 mmol, 100 mol%) in anhydrous THF (1.0 mL) at 0 °C in a sealed tube. After the addition was complete, the reaction mixture was stirred for 20 minutes at 0 °C and the progress of the reaction was monitored by TLC. Upon completion, water (1 drop) was added to the reaction mixture, followed by the addition of 15% w/w NaOH aqueous solution (1 drop) and water (2 drops). The resulting suspension was then warmed to r.t. and stirred for 15 minutes before anhydrous Na₂SO₄ was added. The mixture was stirred for an additional 15 minutes before filtration. The filtrate was collected, and the solvent was removed in vacuo to provide the amino aldehyde intermediate which could be used in the next step without purification. A solution of the above synthesized amino aldehyde intermediate in MeOH (1.0 mL) was stirred at 0 °C in a sealed tube. NaBH4 (15.1 mg, 0.40 mmol, 400 mol%) was then added to the stirring solution. Then the solution was stirred at ambient temperature for 1 hour. Upon completion, the reaction mixture was transferred to a separatory funnel and water (approx. 5.0 mL) was added. The aqueous phase was extracted with EtOAc (approx.3 × 10.0 mL). The combined organic phases were dried over anhydrous MgSO4. The concentration of the filtrate in vacuo was followed by FCC (hexane/EtOAc 25:75) to afford the desired product (12.1 mg, 50%, over 2 steps, d.r. >20:1, e.r. = 99:1) as a colorless oil. [^]^ ^^ = +26.4 (c = 1.0 CHCl3); IR (thin film) νmax/cm⁻¹: 3399 (br), 2964 (s), 2928 (s), 1600 (s), 1495 (s), 1317 (s), 1261 (s), 747 (s), 691 (s); 1H NMR (500 MHz, CDCl3) δ 7.33 – 7.21 (m, 5H, H¹² + H¹³ + H¹⁴), 7.16 – 7.13 (m, 2H, H⁷), 6.73 – 6.70 (m, 1H, H⁸), 6.62 (d, J = 7.5 Hz, 2H, H⁶), 3.76 – 3.68 (m, 2H, H²), 3.61 – 3.26 (m, 2H, H³ + H⁴), 3.19 – 3.14 (m, 1H, H⁹), 1.91 (br s, 1H, H¹), 1.35 (d, J = 7.0 Hz, 3H, H¹⁰); 13C NMR (126 MHz, CDCl₃) δ 147.9 (C⁵), 142.7 (C¹¹), 129.3 (C⁷), 128.6 (C¹³), 127.9 (C¹²), 126.8 (C¹⁴), 118.0 (C⁸), 113.9 (C⁶), 62.5 (C²), 60.2 (C³), 41.0 (C⁹), 18.1 (C¹⁰); HRMS (ESl): calculated for C16H20NO [M+H]⁺ requires m/z 242.1539, found m/z 242.1540; Chiral SFC: YMC Chiral ART Cellulose-SC column (25 cm), CO2:i-PrOH 92:8, 2.0 mL/min, 140 bar, 40 °C. Retention times: 6.4 mins (minor), 7.1 mins (major), e.r. = 99:1. (2S,3S)-3-Phenyl-2-(phenylamino)butanal (51): wise, to a solution of 3f 0 °C in a sealed tube. After the addition was complete, the reaction mixture was stirred for 20 minutes at 0 °C and the progress of the reaction was monitored by TLC. Upon completion, water (1 drop) was added to the reaction mixture, followed by the addition of 15% w/w NaOH aqueous solution (1 drop) and water (2 drops). The resulting suspension was then warmed to r.t. and stirred for 15 minutes before anhydrous Na2SO4 was added. The mixture was stirred for an additional 15 minutes before filtration. Concentration of the filtrate in vacuo was followed by FCC (hexane/EtOAc 10:90) to afford the desired product (16.3 mg, 68%, d.r. >20:1, e.r. = 98.5:1.5) as a colorless oil. [^]^ ^^ = +17.7 (c = 1.0 CHCl₃); IR (thin film) ν_max/cm⁻¹: 3404 (br), 3027 (s), 2970 (s), 2931 (s), 1726 (s), 1599 (s), 1494 (s), 1310 (s), 1266 (s), 748 (s), 698 (s); 1H NMR (500 MHz, CDCl₃) δ 9.53 (d, J = 2.5 Hz, 1H, H¹), 7.39 – 7.28 (m, 5H, H¹¹ + H¹² + H¹³), 7.19 – 7.15 (m, 2H, H⁶), 6.76 – 6.73 (m, 1H, H⁷), 6.60 (d, J = 7.5 Hz, 2H, H⁵), 4.21 – 3.95 (m, 2H, H² + H³), 3.43 – 3.38 (m, 1H, H⁸), 1.38 (d, J = 7.0 Hz, 3H, H⁹); 13C NMR (126 MHz, CDCl3) δ 202.3 (C¹), 146.6 (C⁴), 140.8 (C¹⁰), 129.4 (C⁶), 129.0 (C¹²), 127.8 (C¹¹), 127.4 (C¹³), 118.4 (C⁷), 113.3 (C⁵), 67.3 (C²), 39.7 (C⁸), 17.1 (C⁹); HRMS (ESl): calculated for C + 16H18NO [M+H] requires m/z 240.1383, found m/z 240.1389; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO2:i-PrOH 95:5, 1.0 mL/min, 140 bar, 40 °C. Retention times: 15.3 mins (major), 16.4 mins (minor), e.r. = 98.5:1.5. N-((2S,3S)-1-Morpholino-3-phenylbutan-2-yl)aniline (52): To s THF (1.0 mL), was added a s l%) under N2 at r.t. Then the mixture was heated to 90 °C for 4 hours and the progress of the reaction was monitored by TLC. Upon completion, the mixture was cooled to 0 °C and water (5.0 mL) was slowly added. The mixture was extracted with EtOAc (approx.3 × 10.0 mL). The combined organic phases were dried over anhydrous MgSO4. Concentration of the filtrate in vacuo was followed by FCC (hexane/EtOAc 35:65) to afford the desired product (21.4 mg, 69%, d.r. >20:1, e.r. = 99:1) as a colorless oil. [^]^ ^^ = -7.9 (c = 1.0 CHCl3); IR (thin film) νmax/cm⁻¹: 3366 (br), 2961 (s), 2852 (s), 1601 (s), 1504 (s), 1117 (s), 748 (s), 693 (s); 1H NMR (500 MHz, CDCl3) δ 7.40 – 7.26 (m, 5H, H¹³ + H¹⁴ + H¹⁵), 7.22 – 7.19 (m, 2H, H⁸), 6.73 – 6.68 (m, 3H, H⁷ + H⁹), 3.78 – 3.61 (m, 6H, H¹ + H⁴ + H⁵), 3.49 – 3.44 (m, 1H, H¹⁰), 2.56 – 2.17 (m, 6H, H² + H³), 1.38 (d, J = 7.0 Hz, 3H, H¹¹);13C NMR (126 MHz, CDCl₃) δ 148.2 (C⁶), 142.4 (C¹²), 129.3 (C⁸), 128.4 (C¹⁴), 128.3 (C¹³), 126.5 (C¹⁵), 117.2 (C⁹), 113.2 (C⁷), 66.9 (C¹), 59.3 (C³), 54.5 (C⁴), 53.6 (C²), 39.9 (C¹⁰), 16.2 (C¹¹); HRMS (ESl): calculated for C₂₀H₂₇N₂O [M+H]⁺ requires m/z 311.2118, found m/z 311.2133; Chiral SFC: DAICEL CHIRALCEL OD-H column (25 cm), CO₂:i-PrOH 90:10, 2.0 mL/min, 140 bar, 40 °C. Retention times: 5.8 mins (minor), 7.3 mins (major), e.r. = 99:1. (2S,3S)-1,3-Diphenyl-2-(phenylamino)butan-1-one (53): To a solution of 3f (32.4 mg, 0.10 mmol, 100 mol%) in anhydrous THF (1.0 mL), a solution of PhLi in Et₂O (1.9 M, 105 µL, 0.20 mmol, 200 mol%) was then added dropwise over 3 minutes under N₂ at 0 °C. Then the mixture was stirred at 0 °C for 15 minutes and the progress of the reaction was monitored by TLC. Upon completion, water (5.0 mL) was slowly added to the mixture to quench excess PhLi. The mixture was extracted with EtOAc (approx.3 × 10.0 mL). The combined organic phases were dried over anhydrous MgSO4. The concentration of the filtrate in vacuo was followed by FCC (EtOAc/hexane 10:90) to afford the desired product (28.4 mg, 90%, d.r. >20:1, e.r. = 99:1) as a colorless oil. [^]^ ^^ = +66.4 (c = 1.0 CHCl3); IR (thin film) ν /cm⁻¹: 3379 (br), 3027 (s), 168 1 max 2 (s), 1601 (s), 1506 (s), 748 (s), 693 (s); H NMR (500 MHz, CD2Cl2) δ 7.93 (d, J = 7.5 Hz, 2H, H³), 7.61 – 7.58 (m, 1H, H¹), 7.49 – 7.46 (m, 2H, H²), 7.26 – 7.18 (m, 3H, H¹⁶ + H¹⁷), 7.12 – 7.08 (m, 4H, H¹⁰ + H¹⁵), 6.68 – 6.65 (m, 3H, H⁹ + H¹¹), 5.19 (d, J = 5.0 Hz, 1H, H⁶), 4.37 (br s, 1H, H⁷), 3.45 – 3.40 (m, 1H, H¹²), 1.44 (d, J = 7.0 Hz, 3H, H¹³); 13C NMR (126 MHz, CD₂Cl₂) δ 200.4 (C⁵), 147.8 (C⁸), 141.4 (C¹⁴), 136.3 (C⁴), 133.5 (C¹), 129.3 (C¹⁰), 128.9 (C³), 128.4 (C¹⁶), 128.3 (C²), 128.2 (C¹⁵), 127.0 (C¹⁷), 118.2 (C¹¹), 114.0 (C⁹), 63.5 (C⁶), 42.9 (C¹²), 18.2 (C¹³); HRMS (ESl): calculated for C22H21NONa [M+Na]⁺ requires m/z 338.1515, found m/z 338.1524; Chiral SFC: DAICEL CHIRALCEL IE column (25 cm), CO2:i-PrOH 95:5, 1.0 mL/min, 140 bar, 40 °C. Retention times: 41.4 mins (minor), 51.6 mins (major), e.r. = 99:1. (S)-N-(2-Phenylpropyl)aniline (54): To (0.1 mL) and water (0.1 mL), concentrated sulfuric acid (0.3 mL) was then added dropwise over 2 minutes at r.t. The mixture was then stirred at 120 °C for 72 hours and the progress of the reaction was monitored by TLC. Upon completion, the mixture was cooled down and diluted with water (5.0 mL). This was followed by the addition of 2N aqueous NaOH until a pH value of 9–10 was achieved. The mixture was extracted with EtOAc (approx.3 × 10.0 mL). The combined organic phases were dried over anhydrous MgSO4. Concentration of the filtrate in vacuo was followed by FCC (EtOAc/hexane 2:98) to afford the desired product (9.5 mg, 45%, e.r. = 97:3) as a colorless oil. [^]^^ ^ = -24.8 (c = 1.0 CHCl₃); IR (thin film) ν_max/cm⁻¹: 3415 (br), 3026 (s), 2961 (s), 1602 (s), 1506 (s), 1320 (s), 748 (s), 693 (s); 1H NMR (500 MHz, CD 10 2Cl2) δ 7.35 – 7.23 (m, 5H, H + H¹¹ + H¹²), 7.18 – 7.15 (m, 2H, H²), 6.72 – 6.69 (m, 1H, H¹), 6.60 (d, J = 7.5 Hz, 2H, H³), 4.09 (br s, 1H, H⁵), 3.37 – 3.23 (m, 2H, H⁶), 3.11 – 3.04 (m, 1H, H⁷), 1.35 (d, J = 7.0 Hz, 3H, H⁸); HRMS (ESl): calculated for C₁₅H₁₈N [M+H]⁺ requires m/z 212.1434, found m/z 212.1433; Chiral SFC: DAICEL CHIRALCEL IE column (25 cm), CO2:i-PrOH 90:10, 2.0 mL/min, 140 bar, 40 °C. Retention times: 3.0 mins (major), 3.3 mins (minor), e.r. = 97:3. The spectroscopic properties were consistent with the data available in the literature.¹⁷ (2S,3S)-2-Amino-N,N-dimethyl-3-phenylbutanamide (55): To and water (0.5 mL), added portion-wise at of the reaction was monitored by TLC. Upon completion, the mixture was cooled to 0 °C and a saturated Na2S2O3 solution (approx. 0.2 mL) was slowly added to quench excess PIFA. The mixture was extracted with dichloromethane (approx. 5 × 5.0 mL). The combined organic phases were dried over anhydrous MgSO4. The concentration of the filtrate in vacuo was followed by FCC (basic Al₂O₃, dichloromethane/MeOH 90:10) to afford the desired product (19.8 mg, 96%, d.r. >20:1, e.r. = 98:2) as a pale-yellow oil. [^]^ ^^ = +10.1 (c = 1.0 CHCl₃); 1H NMR (500 MHz, CD₂Cl₂) δ 7.34 – 7.20 (m, 5H, H⁸ + H⁹ + H¹⁰), 3.82 (d, J = 8.5 Hz, 1H, H³), 3.05 – 3.00 (m, 4H, H¹ + H⁵), 2.99 (s, 3H, H^1’), 1.58 (br s, 2H, H⁴), 1.24 (d, J = 7.0 Hz, 3H, H⁶); HRMS (ESl): calculated for C12H18N2ONa [M+Na]⁺ requires m/z 229.1311, found m/z 229.1317; Chiral SFC: DAICEL CHIRALCEL IE column (25 cm), CO2:MeOH (with 0.5% TEA) 80:20, 2.0 mL/min, 170 bar, 40 °C. Retention times: 6.5 mins (minor), 7.8 mins (major), e.r. = 98:2. The spectroscopic properties were consistent with the data available in the literature.¹⁸ Synthesis of (2S,3S)-2-Amino-3-phenyl-butyric acid hydrochloride 56, (2S,3S)-2-amino- 3-phenylbutan-1-ol 57 and (2S,3S)-3-phenyl-2-(phenylamino)butan-1-ol 58: To a solution of 55 (103 mg, 0.50 mmol, 100 mol%) in AcOH (2.5 mL), concentrated hydrochloric acid (2.5 mL) was then added dropwise over 2 minutes at r.t. The mixture was then stirred at 130 °C for 48 hours and the progress of the reaction was monitored by TLC. After cooling to r.t., the solvents were removed in vacuo, the solid was then washed with EtOAc and dried under vacuum to afford 56 as a brown solid. The solid was used in the next step without further purification. IR (thin film) ν_max/cm⁻¹: 3386 (br), 2973 (s), 1732 (s), 1646 (s), 1497 (s), 1468 (s), 1228 (s), 703 (s); 1H NMR (500 MHz, D₂O) δ 7.48 – 7.37 (m, 5H, H⁶ + H⁷ + H⁸), 4.12 (d, J = 7.5 Hz, 1H, H²), 3.46 – 3.40 (m, 1H, H³), 1.46 (d, J = 7.0 Hz, 3H, H⁴);13C NMR (126 MHz, D2O) δ 171.8 (C¹), 139.3 (C⁵), 129.3 (C⁷), 128.2 (C⁸), 127.8 (C⁶), 59.2 (C²), 34.5 (C³), 17.0 (C⁴). To the above solid, a solution of LiAlH4 in THF (1.0 M, 1.1 mL, 1.10 mmol, 220 mol%) was then added dropwise over 2 minutes under N₂ at r.t. The mixture was then stirred at 70 °C for 12 hours and the progress of the reaction was monitored by TLC. Upon completion, the mixture was cooled to 0 °C and 5 drops of water were slowly added. This was followed by addition of 15% w/w NaOH aqueous solution (5 drops) and water (5 drops). The resulting suspension was then warmed to r.t. and stirred for 15 minutes before anhydrous Na2SO4 was added. The mixture was stirred for additional 15 minutes before filtration. The concentration of the filtrate in vacuo to afford the desired product 57 (66.0 mg, 80%, over 2 steps, d.r. >20:1) as a colorless oil. [^]^ ^^ = -17.7 (c = 1.0 CHCl₃); IR (thin film) ν_max/cm⁻¹: 3356 (br), 2963 (s), 2929 (s), 1582 (s), 1494 (s), 1453 (s), 1040 (s), 763 (s), 702 (s); 1H NMR (500 MHz, CDCl3) δ 7.33 – 7.19 (m, 5H, H⁸ + H⁹ + H¹⁰), 3.78 – 3.75 (m, 1H, H²), 3.44 – 3.40 (m, 1H, H^2’), 2.96 – 2.92 (m, 1H, H³), 2.71 – 2.64 (m, 1H, H⁵), 1.99 (br s, 3H, H¹ + H⁴), 1.26 (d, J = 7.0 Hz, 3H, H⁶); 13C NMR (126 MHz, CDCl₃) δ 144.2 (C⁷), 128.7 (C⁹), 127.8 (C⁸), 126.6 (C¹⁰), 64.4 (C²), 58.0 (C³), 43.7 (C⁵), 18.7 (C⁶); HRMS (ESl): calculated for C10H16NO [M+H]⁺ requires m/z 166.1226, found m/z 166.1221. To a solution of 57 (21.5 mg, 0.13 mmol, 100 mol%) in DMSO (0.3 mL) and water (0.15 mL), iodobenzene (17.5 µL, 0.16 mmol, 120 mol%), NaOH (10.4 mg, 0.26 mmol, 200 mol%) and CuI (1.2 mg, 6.5 μmol, 5 mol%) were sequentially added under N2 at r.t. The mixture was then stirred at 90 °C for 12 hours and the progress of the reaction was monitored by TLC. After cooling to r.t., the mixture was extracted with EtOAc (approx. 3 × 5.0 mL). The combined organic phases were dried over anhydrous MgSO₄. Concentration of the filtrate in vacuo was followed by FCC (EtOAc/hexane 25:75) to afford the desired product 58 (19.4 mg, 62%, d.r. >20:1, e.r. = 98:2) as a colorless oil. [^]^ ^^ = +27.4 (c = 1.0 CHCl3); IR (thin film) νmax/cm⁻¹: 3399 (br), 2964 (s), 2928 (s), 1600 (s), 1495 (s), 1317 (s), 1261 (s), 747 (s), 691 (s); 1H NMR (500 MHz, CDCl3) δ 7.33 – 7.21 (m, 5H, H¹² + H¹³ + H¹⁴), 7.16 – 7.13 (m, 2H, H⁷), 6.73 – 6.70 (m, 1H, H⁸), 6.62 (d, J = 7.5 Hz, 2H, H⁶), 3.76 – 3.68 (m, 2H, H²), 3.61 – 3.26 (m, 2H, H³ + H⁴), 3.19 – 3.14 (m, 1H, H⁹), 1.91 (br s, 1H, H¹), 1.35 (d, J = 7.0 Hz, 3H, H¹⁰); 13C NMR (126 MHz, CDCl₃) δ 147.9 (C⁵), 142.7 (C¹¹), 129.3 (C⁷), 128.6 (C¹³), 127.9 (C¹²), 126.8 (C¹⁴), 118.0 (C⁸), 113.9 (C⁶), 62.5 (C²), 60.2 (C³), 41.0 (C⁹), 18.1 (C¹⁰); HRMS (ESl): calculated for C16H20NO [M+H]⁺ requires m/z 242.1539, found m/z 242.1543; Chiral SFC: YMC Chiral ART Cellulose-SC column (25 cm), CO2:i-PrOH 92:8, 2.0 mL/min, 140 bar, 40 °C. Retention times: 6.5 mins (minor), 7.2 mins (major), e.r. = 98:2. 4-Bromo-N-((2S,3S)-1-(dimethylamino)-1-oxo-3-phenylbutan-2-yl)benzamide (59): 11 O Me O Me 1 13 4-bromobenzoyl chloride (100 mol%) Me 3 12 Me 1 Et N (2 N 2 10 4 N ₃ 00 mol%) Me 4 O NH 15 4- wise, to 200 mol%) and DCM (1.0 mL) at 0 °C. The reaction was stirred at ambient temperature for 12 hours. Upon completion, the reaction mixture was diluted with DCM (5.0 mL) and transferred to a separatory funnel. The mixture was washed with 1N HCl (10.0 mL). The combined organic phases were dried over anhydrous MgSO₄. The concentration of the filtrate in vacuo was followed by FCC (EtOAc/hexane 40:60) to afford the desired product (25.2 mg, 65%, d.r. >20:1, e.r. = 98:2) as a colorless solid. m.p. = 154 – 156 °C (hexane/EtOAc); [^]^ ^^ = +52.8 (c = 1.0 CHCl₃); IR (thin film) ν_max/cm⁻¹: 3310 (s), 2926 (s), 1621 (s), 1538 (s), 1484 (s), 1335 (s), 698 (s), 648 (s); 1H NMR (500 MHz, CDCl₃) δ 7.51 (s, 4H, H⁷ + H⁸), 7.34 – 7.23 (m, 5H, H¹³ + H¹⁴ + H¹⁵), 6.96 (d, J = 8.5 Hz, 1H, H⁴), 5.35 (t, J = 8.0 Hz, 1H, H³), 3.46 – 3.40 (m, 1H, H¹⁰), 2.97 – 2.96 (m, 6H, H¹), 1.39 (d, J = 7.0 Hz, 3H, H¹¹); 13C NMR (126 MHz, CDCl3) δ170.7 (C²), 165.7 (C⁵), 141.6 (C¹²), 132.8 (C⁶), 131.6 (C⁸), 128.6 (C⁷), 128.5 (C¹⁴), 127.8 (C¹³),127.1 (C¹⁵), 126.1 (C⁹), 53.7 (C³), 42.9 (C¹⁰), 37.3 (C¹), 35.7 (C^1’), 16.9 (C¹¹); HRMS (ESl): calculated for C₁₉H₂₁BrN₂O₂Na [M+Na]⁺ requires m/z 411.0679, found m/z 411.0682; Chiral SFC: DAICEL CHIRALCEL IE column (25 cm), CO₂:i-PrOH 80:20, 2.0 mL/min, 170 bar, 40 °C. Retention times: 7.2 mins (minor), 9.3 mins (major), e.r. = 98:2. The stereochemistry of compound 59 was assigned by single crystal X-ray diffraction of crystals obtained from EtOAc/Hexane (CCDC number: 2245009) (2S,3S)-2-Amino-N,3-diphenylbutanamide (60): To a solution of 30 (34.6 mg, 0.10 mmol, 100 mol%) in CH3CN (1.0 mL) and water (0.5 mL), (bis(trifluoroacetoxy)iodo)benzene (51.6 mg, 0.12 mmol, 120 mol%) was slowly added, portion-wise, at 0 °C. The mixture was then stirred at 0 °C for 1 hour and the progress of the reaction was monitored by TLC. Upon completion, saturated Na₂S₂O₃ solution (0.2 mL) was slowly added to the mixture to quench excess PIFA at 0 °C. The mixture was extracted with dichloromethane (approx. 5 × 5.0 mL). The combined organic phases were dried over anhydrous MgSO4. The concentration of the filtrate in vacuo was followed by FCC (basic Al2O3, EtOAc/hexane 65:35) to afford the desired product (22.9 mg, 90%, d.r. >20:1, e.r. = 93:7) as a pale-yellow oil. [^]^ ^^ = -84.1 (c = 1.0 CHCl3); IR (thin film) νmax/cm⁻¹: 3301 (br), 3060 (s), 2928 (s), 1666 (s), 1600 (s), 1523 (s), 1443 (s), 755 (s), 701 (s); 1H NMR (500 MHz, CDCl3) δ 9.15 (s, 1H, H⁵), 7.54 (d, J = 8.0 Hz, 2H, H³), 7.35 – 7.22 (m, 7H, H² + H¹² + H¹³ + H¹⁴), 7.11 – 7.08 (m, 1H, H¹), 3.61 (d, J = 6.0 Hz, 1H, H⁷), 3.47 – 3.41 (m, 1H, H⁹), 1.93 (br s, 2H, H⁸), 1.42 (d, J = 7.0 Hz, 3H, H¹⁰); 13C NMR (126 MHz, CDCl₃) δ 172.0 (C⁶), 141.5 (C¹¹), 137.6 (C⁴), 128.9 (C²), 128.7 (C¹³), 128.0 (C¹²), 127.1 (C¹⁴), 124.1 (C¹), 119.6 (C³), 61.3 (C⁷), 42.6 (C⁹), 18.4 (C¹⁰); HRMS (ESl): calculated for C16H19N2O [M+H]⁺ requires m/z 255.1492, found m/z 255.1494; Chiral SFC: DAICEL CHIRALCEL IE column (25 cm), CO2:MeOH (with 0.5% TEA) 90:10, 2.0 mL/min, 140 bar, 40 °C. Retention times: 23.9 mins (minor), 33.9 mins (major), e.r. = 93:7. (2S,3S)-2-Amino-3-(1H-indol-3-yl)-N,N-dimethylbutanamide (62): To a solution of 18a (49.1 mg, 0.10 mmol, 100 mol%) in CH₃CN (1.0 mL) and water (0.5 mL), (bis(trifluoroacetoxy)iodo)benzene (51.6 mg, 0.12 mmol, 120 mol%) was slowly added, portion-wise, at 0 °C. The mixture was then stirred at 0 °C for 1 hour and the progress of the reaction was monitored by TLC. Upon completion, saturated Na2S2O3 solution (0.2 mL) was slowly added to the mixture to quench excess PIFA at 0 °C. The mixture was extracted with dichloromethane (approx. 5 × 5.0 mL). The combined organic phases were dried over anhydrous MgSO₄. The concentration of the filtrate in vacuo was followed by FCC (basic Al2O3, dichloromethane/MeOH 90:10) to afford the amide intermediate 61 (38.3 mg, 96%, d.r. >20:1) as a pale-yellow oil. The above amide intermediate (39.9 mg, 0.10 mmol, 100 mol%) in DMA (0.50 mL) was slowly added to a solution of NaH (8.00 mg, 0.20 mmol, 200 mol%) in DMA (0.25 mL) at r.t. The mixture was then stirred at 60 °C for 3 hours and the progress of the reaction was monitored by TLC. After cooling to 0 °C, water (approx.5.0 mL) was added to the reaction mixture and then extracted with EtOAc (approx.5 × 10.0 mL). The combined organic phases were dried over anhydrous MgSO4. The concentration of the filtrate in vacuo was followed by FCC (basic Al₂O₃, dichloromethane/MeOH 80:10) to afford the desired product 62 (20.1 mg, 82%, d.r. >20:1, e.r. = 96:4) as a pale-yellow solid. m.p. = 92 – 94 °C (hexane/EtOAc); [^]^^ ^ = +42.7 (c = 1.0 CHCl3); IR (thin film) νmax/cm⁻¹: 3261 (br), 2925 (s), 1631 (s), 1458 (s), 1343 (s), 1110 (s), 742 (s); 1H NMR (500 MHz, CDCl3) δ 8.44 (s, 1H, H¹⁴), 7.60 (d, J = 8.0 Hz, 1H, H⁹), 7.36 (d, J = 8.0 Hz, 1H, H¹²), 7.19 – 7.16 (m, 1H, H¹¹), 7.11 – 7.08 (m, 1H, H¹⁰), 7.05 (s, 1H, H¹⁵), 4.03 (d, J = 8.0 Hz, 1H, H³), 3.40 – 3.35 (m, 1H, H⁵), 3.01 (s, 3H, H¹), 2.96 (s, 3H, H^1’), 2.17 (br s, 2H, H⁴), 1.36 (d, J = 7.0 Hz, 3H, H⁶); 13C NMR (126 MHz, CDCl3) δ 173.9 (C²), 136.5 (C¹³), 126.9 (C⁸), 122.1 (C¹¹ + C¹⁵), 119.4 (C¹⁰), 119.0 (C⁹), 117.2 (C⁷), 111.5 (C¹²), 55.7 (C³), 37.4 (C¹ + C⁵), 35.8 (C^1’), 17.9 (C⁶); HRMS (ESl): calculated for C + 14H20N3O [M+H] requires m/z 246.1601, found m/z 246.1605; Chiral SFC: DAICEL CHIRALCEL IE column (25 cm), CO₂:MeOH (with 0.5% TEA) 80:20, 3.0 mL/min, 170 bar, 40 °C. Retention times: 7.7 mins (minor), 9.4 mins (major), e.r. = 96:4. Formal synthesis of 64 and 65: To a solution of 13n (187 mg, 0.50 mmol, 100 mol%) in AcOH (0.4 mL), concentrated hydrochloric acid (2.0 mL) was added dropwise over 2 minutes at r.t. The mixture was then stirred at 150 °C for 72 hours and the progress of the reaction was monitored by TLC. Upon completion, the mixture was cooled to r.t. and diluted with water (5.0 mL). This was followed by addition of 2N aqueous NaOH until a pH value of 9–10 was achieved. The mixture was extracted with EtOAc (approx.3 × 10.0 mL). The combined organic phases were dried over anhydrous MgSO4. Concentration of the filtrate in vacuo was followed by FCC (EtOAc/hexane 25:75) to afford the amine intermediate 63 (71.8 mg, 55%) as a colorless oil. To a solution of 63 (39.2 mg, 0.15 mmol, 100 mol%) in CH₃CN (1.5 mL) and water (0.75 mL), (bis(trifluoroacetoxy)iodo)benzene (77.4 mg, 0.18 mmol, 120 mol%) was added portion-wise, at 0 °C. The mixture was then stirred at 0 °C for 1 hour and the progress of the reaction was monitored by TLC. Upon completion, the mixture was cooled to 0 °C and saturated Na2S2O3 solution (0.2 mL) was slowly added to quench excess PIFA. This was followed by addition of 2N aqueous NaOH until a pH value of 10–11 was achieved. The mixture was extracted with dichloromethane (approx. 3 × 5.0 mL). The combined organic phases were dried over anhydrous MgSO₄. The filtrate was concentrated in vacuo to afford the free amine intermediate 64 as a pale-yellow oil. The oil was used in the next step without further purification. To a solution of the above free amine intermediate, Et3N (32.0 µL, 0.23 mmol, 150 mol%) in DCM (1.5 mL), and 4-toluenesulfonyl chloride (34.3 mg, 0.18 mmol, 120 mol%) were added portion-wise at 0 °C. The reaction was stirred at r.t. for 16 hours. Upon completion, the reaction mixture was diluted with DCM (5.0 mL) and transferred to a separatory funnel and washed with aq.1N HCl (10.0 mL). The combined organic phases were dried over anhydrous MgSO4. The concentration of the filtrate in vacuo was followed by FCC (EtOAc/hexane 25:75) to afford the desired product 65 (26.9 mg, 56%, over 2 steps, e.r. = 93:7) as a pale-yellow oil. [^]^ ^^ = -10.7 (c = 1.0 CHCl 1 3); H NMR (500 MHz, CDCl3) δ 7.65 (d, J = 8.0 Hz, 2H, H⁴), 7.29 (d, J = 8.0 Hz, 2H, H³), 7.22 – 7.18 (m, 2H, ArH), 6.99 – 6.96 (m, 2H, ArH), 4.30 – 4.28 (m, 1H, H⁶), 3.21 – 3.16 (m, 1H, H⁷), 3.01 – 2.96 (m, 1H, H^7’), 2.88 – 2.82 (m, 1H, H⁸), 2.43 (s, 3H, H¹), 1.21 (d, J = 6.9 Hz, 3H, H⁹); Chiral SFC: YMC Chiral ART Cellulose-SC column (25 cm), CO2:i-PrOH 80:20, 2.0 mL/min, 165 bar, 40 °C. Retention times: 4.9 mins (minor), 5.2 mins (major), e.r. = 93:7. 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Claims

CLAIMS 1. A process comprising reacting a carbonyl compound with an alkene compound in the presence of an iridium catalyst, wherein the carbonyl compound comprises a nitrogen- based group in a position that is α or β to the carbonyl group and wherein the process comprises the step of α-alkylation of the carbonyl compound by carbon-carbon bond formation between the carbon atom α to the carbonyl group and a carbon atom of the double bond of the alkene compound.

2. A process as claimed in claim 1 wherein the carbonyl group of the carbonyl compound is part of an amide.

3. A process as claimed in claim 2 wherein the amide is a tertiary amide.

4. A process as claimed in claim 3 wherein the two groups on the nitrogen atom together form a ring.

5. A process as claimed in claim 2 wherein the amide is a secondary amide.

6. A process as claimed in claim 1 wherein the carbonyl group of the carbonyl compound is in the form of a ketone.

7. A process as claimed in any preceding claim wherein the nitrogen-based group of the carbonyl compound is a secondary amine.

8. A process as claimed in claim 7 wherein the secondary amine has the structure -NHAr wherein Ar is an aromatic moiety.

9. A process as claimed in any preceding claim wherein the alkene compound is a monosubstituted alkene.

10. A process as claimed in any of claims 1 to 8 wherein the alkene compound is disubstituted on one of the carbon atoms of the double bond of the alkene.

11. A process as claimed in any preceding claim wherein the iridium catalyst is an iridium (I) catalyst.

12. A process as claimed in any preceding claim wherein the iridium catalyst is a chiral iridium catalyst.

13. A process as claimed in claim 12 wherein the chiral iridium catalyst has a diphosphine ligand.

14. A process as claimed in any preceding claim comprising the charging of a vessel with said carbonyl compound, an iridium compound, a chiral ligand, said alkene compound and solvent, and allowing reaction to occur at elevated temperature.

15. A process as claimed in any preceding claim which is carried out in 1,4-dioxane as solvent.