WO2007117404A2

WO2007117404A2 - Methods and materials for preparing organic compounds from primary amines

Info

Publication number: WO2007117404A2
Application number: PCT/US2007/008221
Authority: WO
Inventors: H. Mario Geysen; Cyrille Gineste
Original assignee: University Of Virginia Patent Foundation
Priority date: 2006-03-31
Filing date: 2007-03-30
Publication date: 2007-10-18
Also published as: WO2007117404A3; WO2007117404A9

Abstract

Methods are disclosed for the conversion of primary amines to other functional groups. The methods can be used to prepare chiral organic compounds, including organic alcohols and organic halides. The methods can be carried out by treating a primary amine with an activating agent and a nitrosyl agent to produce the transformed compound along with nitrous oxide.

Description

METHODS AND MATERIALS FOR PREPARING ORGANIC COMPOUNDS

FROM PRIMARY AMINES

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application Serial No. 60/787,830 filed March 31, 2006, the disclosure of which is incorporated by reference in its entirety herein.

BACKGROUND

[0002] There is a constant need for new and different molecules having unique structures for use in the treatment of diseases and, more generally, for the advancement of science. While recent advances in organometallic chemistry have expanded synthetic strategies to create new carbon carbon bonds, much synthetic organic chemistry still relies on well known functional groups for the creation of new compounds. New synthetic strategies must be economically practical before they will find widespread use in the pharmaceutical or industrial context^".

[0003] One well known synthetic strategy is the conversion of an amino group to a leaving group, for example halogen, or to another functional group, for example hydroxyl. In the past this reaction has been considered practical only for aromatic amines. The reaction was known as early as 1849 and has been the subject of much research and analysis in the succeeding years. During this time no simple alternative transformation has been identified, despite the obvious importance to, for example, medicinal chemistry where nitrogen chemistry is central. The archetype of this reaction is a diazonium mediated transformation with resultant liberation of dinitrogen. This reaction has been considered to be of little synthetic utility with simple alkyl amines, a viewpoint that is well documented by general organic chemistry textbooks. Even in synthetic schemes that are amenable to diazonium reactions, challenges exist with regard to scale-up.

[0004] Another consideration with functional group transformations is the creation, incorporation and maintenance of chirality. While a limited number of reactions are known that provide control over chirality, a common method is to utilize chiral building blocks isolated from nature as starting materials. Amino acids are one significant source of chiral molecules. If a method for transforming the functional groups of the amino acids into other types of functional groups could be found, then amino acids could be used as starting materials for the preparation of a wide variety of chiral compounds.

[0005] A number of amino acid-based compounds having α-hydroxy and α-halo acids have been prepared using a diazotization process. For example, Souers et. al.(Synthesis, No. 4, 583-85 (1999)) purports to have demonstrated the conversion of amino acids to α-bromo acids, via a diazotization process with sodium nitrite, potassium bromide and 0.75 M HBr at -4 to -7 ⁰C. The yields were said to be between 54 and 86 %, with greater than 95% retention of stereochemistry. Reactions were noted as "vigorously exothermic." In addition, Shin et. al.(Journal of Organic Chemistry, Vol. 65, 7667-75 (2000)) purports to have converted 7 naturally-occurring amino acids to α- hydroxy acids via a diazotization process using sodium nitrite and acid, either sulfuric, hydrochloric or acetic, at 0⁰C. In 2004, Deegchongkit et. al. (Organic Letters, Vol. 6(4), 497-500 (2004)) reportedly developed chemistry to produce 18 chiral α-hydroxy acids which were said to be derived from 18 chiral amino acids (glycine being achiral, proline being a secondary amine.) Deegchongkit et. al. also utilized a diazotization process, with sodium nitrite and acid, and noted that only 15 of 18 worked by this process. They also noted that the preparation of some compounds were problematic due to side chain incompatibility with the acidic or oxidizing conditions, or due to intramolecular attack of side chains. Cupido et. al. {Tetrahedron Letters, Vol. 46, 6733- 35, (2005)) noted that intramolecular attack was problematic_. in several compounds by Deegchongkit et. al., and provided some improvement in the yields for arginine-like amino acids. Cupϊdo's reaction was also accomplished by a diazotization process.

[0006] New and facile methods are needed for the conversion of the functional group of primary amines to other groups. Ideally, the methods will be useful for the production of chiral compounds. In addition, the methods should be simple to carry out, quick and efficient (e.g., quantitative).

SUMNdARY

[0007] Methods and materials are disclosed for the conversion of primary amines to other functional groups. The methods can be used to prepare organic compounds, including chiral organic compounds. The methods can be carried out by reacting a primary amine with an activating agent and a nitrosyl agent to produce an organic compound and nitrous oxide. The methods can be simple, quick and efficient (e.g., quantitative). . ^• .

[0008] Methods are disclosed for preparing organic compounds, including organic alcohols and organic halides. In such methods, primary amines can be reacted • with activating agents and nitrosyl agents to produce such organic compounds along with nitrous oxide. Methods are also disclosed in which a primary organic N-haloamine or N,N-dihaloamine can be reacted with a nitrosyl agent to produce the organic compound and nitrous oxide. Methods are also disclosed for preparing an α-hydroxy acid or derivative thereof by treating a α-amino acid or derivative thereof with an activating agent and a nitrosyl agent, with resulting generation of nitrous oxide. Novel compounds and compositions prepared by the methods are also disclosed.

[0009] The disclosed compounds, compositions or methods can be used in a number of processes, including large scale and commercial processes, and in a wide variety of useful products including, for- example, bromides, chlorides, chiral bromides derived from chiral amines, α-halo acids, Z)-amino acids from £-amino acids in two steps and in a general procedure for inversion of chiral centers via an amine intermediate. A variety of substituted chemical entities can be prepared from amines using the disclosed methods, for example, azides, cyanides, phenolic ethers and esters. Reagents and reaction mixtures useful for carrying out the conversions of amines to the corresponding products are also disclosed. Fqr example, reagents useful for converting amines to the corresponding- halides can include halides and inter-halides, N-halo reagents, nitroso and nitryl reagents and hydroxyl halides.

[0010] Additional features and advantages are described herein, and will be apparent from the following Detailed Description and the Figures.

BRIEF DESCRIPTION OF THE FIGURES

[0011] Figure 1 provides a mass spectra for the reaction of 1.0 equivalent each of amyl nitrite and Br₂ with aniline (a; upper, panel) and with 3-aminomethylpyridϊne (AMP; b; lower panel).

[0012] Figure 2 provides an^" infrared spectrum of the N₂O evolved from the reaction of AMP and 1.1 equivalents of isoamyl nitrite and 5.0 equivalents bromine. . [0013] Figure 3 provides analytical HPLC traces for the two amines, AMP (trace a) and 2-(2-aminoethyl)pyridine (AEP - trace b), before and after addition of 1.1 equivalent isoairiyl nitrite and 5.0 equivalents of Efø.

[0014] Figure 4 provides an HPLC trace of a α-bromo acid converted from the amino acid Tyr(tBu).

[0015] Figure 5 provides HPLC traces of three α-bromo acids converted from the amino acids Trp(Boc), Asp(OtBu), and His(Trt).

[0016] Figure 6 provides HPLC traces of three α-bromo acids converted from the amino acids Lys(Fmoc). Phe, and Lys(Boc).

[0017] Figure 7 provides graphs demonstrating the disappearance of AMP and appearance of 3-bromomethylpyridine as a function of equivalents of isoamyl nitrite and Br₂ added.

DETAILED DESCRIPTION

[0018] Methods are provided for converting primary amines to other organic compounds with the resultant production of nitrous oxide. Methods as disclosed herein can result in the production of new organic compounds having a new functional group in place of the amine in the starting material. A wide variety of substitutions are possible. For example, substitutions can include azide, cyanide, phenol ether and ester substitutions. In some embodiments, the new functional group can be a hydroxyl group, resulting in an organic alcohol. In other embodiments, the functional group can be a halide, resulting in an organic halide.

[0019] Methods are provided that can be carried out with an activating agent and a nitrosyl agent The activating agent can be any compound that can activate the amine. In preferred methods, the activating agent can halogenate the amine to generate an N- haloamine or an N,N-dihaloamine. In other methods, the activating agent can include but is not limited to an alkyl nitrite and X₂, XNO2, HOX, an alkyl hypohalite, cyanogen bromide, NO₂-BX₄ and X₂, N-halosuccinimide, l-(chloromethyl)-4-fluoro-l,4- diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (e.g. SELECTFLUOR^®), or cyanuric halide, wherein X is F, Cl, Br, or I. In some preferred embodiments, the activating agent can be N-bromosuccinide. Alternatively, it can be isoamyl nitrite and bromine; sodium nitrite and bromine; cyanuric bromide; cyanuric chloride; or cyanuric fluoride.

[0020] Any nitrosyl agent that can convert either the primary amine or the activated amine into the desired organic compound can be used. The nitrosyl agent can be added with the activating agent to a reaction mixture or it can be added separately from the activating agent. The activating agent and nitrosyl agent can be different from one another, or can be the same.

[0021] Useful nitrosyl agents that can cause the production of an organic halide can include, but is not necessarily limited to, XNO, NO-BX4 and X₂, HONO and X2, NaNO2 and trifluoroacetic acid and X₂, NaNO2 and acetic acid and X2, Na₂Fe(CN)S(NO) and X₂, or a nitrite and an acid and X2, wherein X is Br, Cl or F. In a preferred embodiment to produce the organic halide, the nitrosyl agent can be BrNO, HNO2 and bromine, NaNO2 and trifluoroacetic acid and Br₂, cyanuric chloride and NO- BF4, cyanuric fluoride and NO-BF₄, or cyanuric bromide and NO-BF₄.

[0022] Useful nitrosyl agents that can cause the production of the organic alcohol include, but are not limited to, NO₂-BX₄ and trifluoroacetic acid, HONO, NaNO₂ and trifluoroacetic acid, NaNO₂ and acetic acid, or a nitrite and an acid, wherein X is Br, Cl or F. The nitrosyl agent can be generated by the any combination of nitrite salt and acid, e.g. any organic or inorganic nitrite salt and any organic or inorganic acid. In preferred methods, the organic alcohol can be prepared from the nitrosyl agent HONO or NaNO₂ and trifluoroacetic acid.

[0023] The activating agent and the nitrosyl agent can be in the form of one or more compounds added directly to the reaction mixture, can be generated in situ in the reaction mixture, or can be formed in the reaction mixture as intermediates of the reaction. In some embodiments, to produce the organic halide, the activating agent and nitrosyl agent can be generated by the combination of alkyl nitrite, X₂, and primary amine, wherein X is F, Cl, Br, or I. In preferred embodiments, the activating agent and nitrosyl agent can be generated by the combination of isoamyl nitrite, Br₂, and primary amine.

[0024] As disclosed herein, the conversion of 3-aminomethylpyridine (AMP) to 3-(bromomethyl)pyridine was studied. The reaction of AMP in methylene chloride produces an off-white precipitate during the addition of one equivalent of each of isoamyl nitrite and Br₂. The precipitate redissolves on the further addition of Br₂. This suggests that the reaction proceeds through an intermediate that is most likely unstable. To identify the intermediates of the reaction directly, both aniline and AMP were reacted with 1 equivalent each of isoamyl nitrite and Br₂, and neat acetonitrile used as the solvent for dilution prior to obtaining mass spectra. Tn contrast to the intermediates formed when aniline is reacted, which indicates a diazo reaction pathway, Figure 1 shows the presence of both the N-bromo and N,N-dibromo intermediates of AMP with very little of the final product 3-(bromomethyl)pyridine present. The three compounds indicated as ionized radicals in trace b of Figure 1 at m/z 93, 108, and 186/188, are the results of fragmentation by loss of a bromine atom during the mass spectroscopy process. On addition of either reagent alone only AMP is observed in the spectrum, suggesting that Br₂ is not reacting directly with the amine.

[0025] While not being bound by a theory, a proposed reaction process for conversion of a primary amine to an organic bromide with isoamyl nitrite and bromine is set forth below in Scheme 1. Conversion of the amine to the N-bromoamine and N,N-dibromoamine can occur with the addition of isoamyl nitrite and bromine. This intermediate then can react with a reactive intermediate, nitrylbromide (BrNC>₂), which can be itself formed by reaction. Confirmation that the isoamyl bromide can result from reaction of isoamyl nitrite with bromine was obtained by GC/MS and by NMR. To account for the almost complete conversion of AMP to 3-(bromomethyl)pyridine as observed by HPLC, an alternative pathway to the N-bromoamine or N,N-dibromoamine intermediates of AMP is postulated as shown by reactions 6 and 7. In this example, the activating agent is hypobromite (HOBr), which can be formed as per reaction 5. Independent confirmation of this was obtained by reacting AMP with either N- bromosuccinimide or a mixture of 4-chloroperoxybenzoic acid and Br₂, and then completing conversion to the 3-(bromomethyl)pyridine by addition of a CH2CI2 solution of nitrous acid and Br₂, reaction 8. Under normal reaction conditions it is thought that nitrosyl bromide (BrNO) can be formed as per reaction 5.

[0026] Formation of 3-(hydroxymethyl) pyridine is postulated to proceed as shown in reaction 9. Without wishing to be bound by any particular theory, this suggests an explanation for the finding that best yields of an organic bromide require about 5 equivalents of total Br₂, and is the result of mass action driven competition for nitrous acid by a large excess of added Br₂, reaction 5. Alternatively, the organic alcohol can be optimized by increasing the amount of nitrous acid in the reaction. SCHEME l

1 isoamyl-N0₂ + Br₂ → isoamyl-Br + BrNO₂

2 R-NH₂ + BrNO₂ → R-NHBr + HNO₂

3 R-NHBr + BrNO₂ → R-NBr₂ + HNO₂ x R-NH₂

4 R-NH₂ + BrNO₂ → y R-NHBr

. z R-NBr₂

5 HNO₂ + Br₂ → HOBr + BrNO

6 R-NH₂ + HOBr → R-NHBr + H₂O

7 R-NHBr + HOBr → R-NBr₂ + H₂O

8 R-NBr₂ + BrNO → R-Br + N₂Ot + Br₂

9 R-NBr₂ + HNO₂ → R-OH + N₂Ot + Br₂

[0027] Because the methods of converting an primary amine to an organic compound are thought to involve an intermediate N-haloamine or N,N-dihaloamine, another method can include the conversion of the primary organic N-haloamine or primary organic N,N-dihaIoamine to the organic compound, wherein the intermediate can be treated with a nitrosyl agent to produce an organic compound and nitrous oxide. The nitrosyl agent can be any nitrosyl agent. For the organic halide, the nitrosyl agent can include any species as set forth above, e.g. XNO, NO-BX₄ and X₂, HONO and X₂, NaNO₂ and trifluoroacetic acid and X₂, NaNO₂ and acetic acid and X₂, Na₂Fe(CN)_S(NO) and X₂, or a nitrite and an acid and X₂, wherein X can be Br, Cl or F. For an organic alcohol, the nitrosyl agent can include any species as set forth above, e.g. NO₂-BX4 and trifluoroacetic acid, HONO, NaNO₂ and trifluoroacetic acid, NaNO₂ and acetic acid, or a nitrite and an acid, wherein X is Br, Cl or F.

[0028] The reaction conditions can include any conditions that allow a facile reaction to occur. The organic amine can be partially dissolved in a solvent. The solvent can be any solvent, including but not limited to tetrahydrofuran, dichloromethane, chloroform, carbon tetrachloride, dimethyl formamide, dimethyl sulfoxide, /-butanol, diethylether, acetic acid, hexane, dichloroethane, ethyl acetate, acetonitrile, methanol, ethanol, bromine, water and the like. Preferably the reaction can be conducted in tetrahydrofuran or dichloromethane.

[0029] The ratio of amine to activating agent to nitrosyl agent can be about 1.0:0.1 :0.1 to about 1:10:100, preferably 1:1:1 to about 1 :5:10, and more preferably 1 :2:3.

[0030] The reaction can be conducted at a range of temperatures, including between about -78 ⁰C and about 200 ⁰C, or -50 °C and about 50 ⁰C, preferably about 25 ⁰C.

[0031] One advantage of the disclosed reactions is that they can be carried out at mild temperatures. This is caused by the facile nature of the reaction in terms of heat generation. The prior art reactions that rely upon the diazo compound to generate nitrogen, while successful with some substrates at small scales, must be conducted at less than 0 °C. Furthermore, that reaction can be hampered in scale-up to multigram scale by the problems with heat generation. A surprising benefit of the disclosed methods is the ability to conduct the reaction at above about 0 ⁰C. Consequently, in some embodiments the reaction can be conducted between about 10 ⁰C and about 40 ⁰C, preferably between about 20 ⁰C and about 30 ⁰C, and more preferably at about room temperature. The yield of the preparation of organic alcohol or organic halide can be greater than about 50%, preferably greater than about 75%, and more preferably greater than about 90% and can be nearly quantitative. Furthermore, because the disclosed reactions can be more facile than the diazo reaction, the conversion of the primary amine can be conducted on a multigram or large scale, including greater than 10 grams, • greater than 100 grams, and greater than 1 kilogram. Finally, the stereochemistry of any chiral primary amine is not lost. Therefore, conversion can occur with greater than about 90% retention of stereochemistry, e.g. about 90% or more, about 91% _. or more, about 92% or more, about 93% or more, about 94% or more, about 95% or more, about 96% or more, about 97% or more, about 98% or more, about 99% or more; preferably greater than about 95% retention of stereochemistry, e.g. about 95% or more, about 96% or more, about 97% or more, about 98% or more, about 99% or more; and most preferably with complete retention of stereochemistry. Complete retention for the purposes of this disclosure is as greater than about 99% retention of configuration.

[0032] Substrates suitable for use with methods as disclosed herein include any primary amines, particularly aliphatic primary amines. One of the differences between methods as disclosed herein and prior methods was that previously known methods were limited to aryl amines and to amino acids in which a neighboring group effect was implicated in the conversion of the amino to a halide or alcohol. In contrast, methods as disclosed herein provide for conversion of simple aliphatic amines, e.g. 2- aminoethylpyridine, 6-aminόhexanoic acid, under facile conditions. Furthermore, the chiral amine i?-(-)-l-methyl-3-phenyIpropylamine, containing no adjacent neighboring group, can be converted to the corresponding bromide with retention of chirality. Consequently, any primary amine can be used in the methods as disclosed herein.

[0033] Furthermore, the disclosed methods can be used to convert any primary amine with retention of stereochemistry. More specifically, any primary amine having a chiral center can be converted to an organic alcohol or organic halide with retention of stereochemistry at the same chiral center.

[0034] Methods for the conversion of amino acids or derivatives thereof, into organic alcohols or organic bromides are also disclosed. Amino acids can include any compound containing an amine and an acid group, or their derivatives, including but not limited to α-amino acids, β-amino acids, achiral amino acids, chiral amino acids, racemic amino acids, enantiomerically enriched amino acids, enantiomerically pure amino acids, diastereomerically enriched amino acids, diastereomerically pure amino acids, and derivatives thereof. In some embodiments, α amino acids include the 20 naturally occurring amino acids, non-naturally occurring amino acids, .D-amino acids, L- amino acids, and mixtures of D- and Z-amino acids, including derivatives thereof.

[0035] Primary amines can include, but are not limited to α-amino acids, β- amino acids, α-amino amides, β-amino amides, α-amino esters, β-amino esters, α-amino aldehydes, β-amino aldehydes, β-amino ether, a β-amino alcohol, γ-amino ether, or a γ- amino alcohol.

[0036] The term "derivatives" as used herein is meant to include but is not limited to esters, ethers, alcohols, aldehydes, amines, weinreb amides, salts, and compounds that contain one or more protecting groups, particularly two or more orthogonal protecting groups. For example derivatives of possible amino acid starting materials include, but are not limited to, derivatives such as α-amino amide, β-amino amide, α-amino ester, β-amino ester, α-amino aldehyde, β-amino aldehyde, β-amino ether, a β-amino alcohol, γ-amino ether, or a γ-amino alcohol, and the corresponding protected versions thereof. [0037] Exemplary amino acid substrates that can be converted by the disclosed methods include l-Boc-piperidine-4-Fmoc-amino-4-carboxylic acid, Boc-(Fmoc- amino)glycine, Boc-Dpr(Fmoc)-OH, Boc-Lys(Fmoc)-OH, Boc-Orn(Fmoc)-OH, Fmoc- (aminomethyl)benzoic acid, Fmoc-11-Aun-OH, Fmoc-12-Ado-OH, Fmoc-2-Me-Ala- OH, Fmoc-3-(4-biphenyl)aIanϊne, Fmoc-3-nitrotyrosine, Fmoc-4,5-dehydroleucine, Fmoc-4-aminomethylphenylacetic acid, Fmoc-4-chlorophenylalanine, Fmoc-5- aminovaleric acid, Fmoc-8-aminocaprylic acid, Fmoc-Ala-OH, Fmoc-Allo-Thr(tBu)- OH, Fmoc-alpha-methylalanine, Fmoc-Arg(Mts)-OH, Fmoc-Arg(N02)-OH, Fmoc- ATg(PmC)-OH₃ Frnoc-Asn(Tmob)-OH, Fmoc-Asn-OH, Fmoc-Asp(O-l-Ada)-OH, Fmoc-Asp(OAllyl)-OH, Fmoc-Asp(Ocyclohexyl)-OH, Fmoc-Asp(OtBu)-OH, Fmoc- benzothienylalanϊne, Fmoc-beta-alanine, Fmoc-beta-cyclopropylalanine, Fmoc-Cha- OH, Fmoc-Cys(Et)-OH, Fmoc-D-2-thienylalanine, Fmoc-D-3-(2-naphthyl)alanine, Fmoc-D-3(3-pyridyl)alanine, Fmoc-D-3,4-dichlorophenylalanine, Fmoc-D-Arg(Tos)- OH, Fmoc-D-Cit-OH, Fmoc-D-cyclohexylglycine, Fmoc-D-Cys(tBu)-OH, Fmoc-delta- amiπobutyric acid, Fmoc-D-Gln-OH, Fmoc-D-homophenylalanine, Fmoc-DL-2- aminotetraline-2-carboxylic acid, Fmoc-D-Leu-OH, Fmoc-DL-p-fluorophenylalanine, Fmoc-D-Lys(nicotinoyl)-OH, Fmoc-D-Met, Fmoc-D-norleucine, Fmoc-D-norvaline, Fmoc-D-Orn(Boc)-OH, Fmoc-D-Ser, Fmoc-D-Thr-OH, Fmoc-D-Tic-OH, Fmoc- Gln(Tmob)-OH, FmOC-GIu(OAlIyI)-OH₅ Fmoc-Gly-Gly-Gly-OH, Fmoc-Gly-Gly-OH, Fmoc-Gly-OH, Fmoc-Gly-Phe-OH, Fmoc-Gly-Pro-Hyp-OH, Fmoc-Gly-Pro-OH, Fmoc- His(Boc)-OH, Fmoc-His(Bum)-OH, Fmoc-His(Bzl)-OH, Fmoc-homophenylalanine, Fmoc-Ile-Pro-OH, Fmoc-L-2-thienylalanine, Fmoc-L-3-(2-naphthyl)alanine, Fmoc-L- 3(3-pyridyl)alanine, Fmoc-L-Gln-OH, Fmoc-L-Glu(OtBu)-OH, Fmoc-Lys(Ac)-OH, Fmoc-Lys(Alloc)-ΘH, Fmoc-Lys(Boc)-OH, Fmoc-Lys(Bzl)-OH, Fmoc-methionine sulfoxide, Fmoc-Nal( I)-OH, Fmoc-Nle-Nle-OH, Fmoc-p-benzylphenylalanine, Fmoc- Phe-GIy-OH, Fmoc-phenylglycine, Fmoc-Phe-OH, Fmoc-Phe-Phe-OH, Fmoc-p- nitrophenyl alanine, Fmoc-S-acetomidomethylcysteine, Fmoc-Ser(Bzl)-OH, Fmoc- Ser(tBu)-OH, Fmoc-tert-leucine, Fmoc-Thr(Bzl)-OH, Fmoc-trans-4-

(aminomethyl)cyclohexanecarboxylϊc acid, Fmoc-Tφ(Boc)-OH, Fmoc-Tφ-OH, Fmoc- Trp-Pro-OH, Fmoc-Tyr(Bzl)-OH, Fmoc-Tyr(Me)-OH, Fmoc-Tyr(tBu)-OH, Fmoc-Tyr- AIa-OH, Fmoc-Tyr-OH, Fmoc-Val, N-alpha-Boc-N-gamma-Fmoc-L-diaminobutyric acid, N-alpha-Fmoc-1-aminocyclopropane-l-carboxylic acid, N-alpha-Fmoc-N-gamma- Boc-diaminobutyric acid, N-alpha-Fmoc-pi-benzyloxymethylhistidine, N-Fmoc-Statin and the like. Of course, the amino protecting group can be removed by methods known in the art prior to the conversion.

[0038] An exemplary set of substrates suitable for conversion to organic compounds such as the product organic alcohols and organic halides by methods disclosed herein can also be described by Formulas T and II.

R² R³ R² R³

(0 (π> wherein Y is OH, Br, Cl or F; R¹, R², R³ can be independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, acyl, substituted acyl, alkoxycarbonyl, substituted alkoxycarbonyl, aryloxycarbonyl, substituted aryloxycarbonyl, carbamoyl, substituted carbamoyl, carboxyl, nitro, cyano, or optionally R¹ and R² together with the carbon atom to which they are attached form a cycloalkyl, substituted cycloalkyl, cycloheteroalkyl or substituted cycloheteroalkyl ring.

[0039] In a class of compounds described by Formula I and Formula II, R¹ is hydrogen and R² is acyl, substituted acyl, alkoxycarbonyl, substituted alkoxycarbonyl, aryloxycarbonyl, substituted aryloxycarbonyl, carboxyl, carbamoyl, substituted carbamoyl, carboxyl, nitro or cyano.

[0040] In a class of compounds described by Formula I and Formula II, R¹ is hydrogen and R³ is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl.

[0041] In a class of compounds described by Formula I and Formula II, R² is acyl, substituted acyl, carboxyl, alkoxycarbonyl, substituted alkoxycarbonyl, aryloxycarbonyl, substituted aryloxycarbonyl, carbamoyl, substituted carbamoyl, nitro or cyano and R³ is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl.

[0042] In a class of compounds described by Formula I and Formula II, R¹ is hydrogen and R² is acyl, substituted acyl, carboxyl, alkoxycarbonyl, substituted alkoxycarbonyl, aryloxycarbonyl, substituted aryloxycarbonyl, carbamoyl, substituted carbamoyl, nitro or cyano and R³ is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl.

[0043] In a class of compounds described by Formula I and Formula II, R¹ is hydrogen and R² is acyl, carboxyl, carbamoyl, substituted carbamoyl, alkoxycarbonyl, or aryloxycarbonyl.

[0044] In a class of compounds described by Formula I and Formula II, R² is acyl, carboxyl, alkoxycarbonyl, or aryloxycarbonyl and R³ is hydrogen, alkyl, substituted alkyl, arylalkyl, substituted arylalkyl, heteroalkyl, substituted heteroalkyl, heteroarylalkyl or substituted heteroarylalkyl.

[0045] In a class of compounds described by Formula I and Formula II, R¹ is hydrogen and R³ is hydrogen, alkyl, substituted alkyl, arylalkyl, substituted arylalkyl, heteroalkyl, substituted heteroalkyl, heteroarylalkyl or substituted heteroarylalkyl.

[0046] In a class of compounds described by Formula I and Formula II, R¹ is hydrogen, R² is acyl, carboxyl, carbamoyl, substituted carbamoyl, alkoxycarbonyl, or aryloxycarbonyl and R³ is hydrogen, alkyl, substituted alkyl, arylalkyl, substituted arylalkyl, heteroalkyl, substituted heteroalkyl, heteroarylalkyl or substituted heteroarylalkyl.

[0047] In a class of compounds described by Formula I and Formula II, R¹ is hydrogen and R² is carboxyl, carbamoyl or substituted carbamoyl.

[0048] In a class of compounds described by Formula I and Formula II, R² is carboxyl, carbamoyl or substituted carbamoyl and R³ is hydrogen, alkyl, substituted alkyl, arylalkyl, substituted arylalkyl, heteroalkyl, substituted heteroalkyl, heteroarylalkyl or substituted heteroarylalkyl.

[0049] In a class of compounds described by Formula 1 and Formula II, R¹ is a hydrogen, R² is carboxyl, carbamoyl or substituted carbamoyl and R³ is hydrogen, alkyl, substituted alkyl, arylalkyl, substituted arylalkyl, heteroalkyl, substituted heteroalkyl, heteroarylalkyl or substituted heteroarylalkyl.

[0050] In a class of compounds described by Formula I and Formula II, R³ is a hydrogen or alkyl group, more preferably R³ is a hydrogen, methyl, isopropyl, isobutyl, .sec-butyl, /"-butyl, cyclopentyl or cyclohexyl group.

[0051] In a class of compounds described by Formula I and Formula II, R³ can be a substituted alkyl group. More preferably R³ can be -CH₂OH, -CH(OH)CH₃, -CH₂CO₂H, -CH₂CH₂CO₂H, -CH₂CONH₂, -CH₂CH₂CONH₂, -CH₂CH₂SCH₃, -CH₂SH, -CH₂(CH₂)₃NH₂ or -CH₂CH₂CH₂NHC(NH)NH₂.

[0052] In a class of compounds described by Formula I and Formula II, R³ can be aryl, arylalkyl, substituted arylalkyl or heteroarylalkyl and even more preferably R³ can be phenyl, benzyl, 4-hydroxybenzyl, 4-imϊdazolylmethyl or 3-indolylmethyl.

[0053] Preferred classes of substrates described by Formula I and Formula II can contain protecting groups, wherein R¹, R² or R³ contains one or more functional groups that are independently attached to a protecting groups. R¹, R² or R³ protecting groups can contain one or more -OH groups that are independently protected as -O-t-butyl, OBzI, -OAc, -OTrityl, or protecting groups commonly used for Ser, Thr, Tyr amino acid sidechains.

[0054] Alternatively, R¹, R² or R³ can contain one or more -NH₂ groups that are independently protected as -NHBoc, -NHBzI, -N(BzI)₂, -N(Bzl)Boc, -NHAc, -NHCbz, -NH(2-Cl-Cbz), -N(Me)₂, -NHCOCF₃, -NHFmoc, -NHDde, NHTrityl. NHMtt, or protecting groups commonly used for Lys or Orn amino acid sidechains. Alternatively, R¹, R² or R³ can contain one or more -NH- groups that are independently protected as -N(Boc)-, — N(Bom)-, — N(tosyl)-, — N(Trityl)-, or protecting groups commonly used for His and Trp amino acid sidechains.

[0055] Alternatively, R¹, R² or R³ can contain one or more -SH groups that are independently protected as — SBzI, -STrityl, -SMtt, or protecting groups commonly used for Cys amino acid sidechains.

[0056] Alternatively, R¹, R² or R³ can contain one or more -COOH group(s) that are independently protected as -COO-t-butyl, -COOBzI, -COOAHyI, -COODmab, or protecting groups commonly used for Asp or GIu amino acid sidechains.

[0057] Alternatively, R¹, R² or R³ can contain one or more -CONH₂ or -NHC(=NH)NH₂ groups that are independently protected as protecting groups commonly used for Asn, GIn or Arg amino acid sidechains.

[0058] Primary amines, in the context of the present disclosure, also encompass salts of the primary amines.

[0059] The following definitions are intended to help clarify this disclosure and are not intended to provide any special meanings as the following terms are to be given their normal meaning as the terms would be understood by one of skill in the art. [0060] "Alkyl," by itself or as part of another substituent, refers to a saturated or unsaturated, branched, straight-chain or cyclic monovalent hydrocarbon radical derived by the removal of one hydrogen atom from a single carbon atom of a parent alkane, alkene or alkyne. Typical alkyl groups include, but are not limited to, methyl; ethyls such as ethanyl, ethenyl, ethynyl; propyls such as propan-1-yl, propan-2-yl, cycloρropan-1-yl, prop-1-en-l-yl, prop-l-en-2-yl, prop-2-en-l-yl (allyl), cycloprop-1-en-l-yl; cycloprop-2-en-l-yl, prop-1-yn-l-yl, prop-2-yn-l-yl, etc.; butyls such as butan-1-yl, butan-2-yl, 2-methyl-propan-l-yl, 2-methyl-propan-2-yl, cyclobutan-1-yl, but-1-en-l-yl, but-l-en-2-yl, 2-methyl-prop-l-en-l-yl, but-2-en-l-yl, but-2-en-2-yl, buta-l,3-dien-l-yl, buta-l,3-dien-2-yl, cyclobut-1-en-l-yl, cyclobut-l-en-3-yl, cyclobuta-l,3-dien-l-yl, but-1-yn-l-yl, but-l-yn-3-yl, but-3-yn-l -yl and the like.

[0061] The term "alkyl" is specifically intended to include groups having any degree or level of saturation, e.g., groups having exclusively single carbon-carbon bonds, groups having one or more double carbon-carbon bonds, groups having one or more triple carbon-carbon bonds and groups having mixtures of single, double and triple carbon-carbon bonds. Where a specific level of saturation is intended, the expressions "alkanyl," "alkenyl," and "alkynyl" are used. In some embodiments, an alkyl group comprises from 1 to 20 carbon atoms (C1-C20 alkyl). In other embodiments, an alkyl group comprises from 1 to 10 carbon atoms (C1-C10 alkyl). In still other embodiments, an alkyl group comprises from 1 to 6 carbon atoms (Ci -Ce alkyl).

[0062] "Alkanyl," by itself or as part of another substituent, refers to a saturated branched, straight-chain or cyclic alkyl radical derived by the removal of one hydrogen atom from a single carbon atom of a parent alkane. Typical alkanyl groups include, but are not limited to, methanyl; ethanyl; propanyls such as propan-1-yl, propan-2-yl (isopropyl), cyclopropan-1-yl, etc.; butanyls such as butan-1-yl, butan-2-yl (see-butyl), 2-methyl-propan-l-yl (isobutyl), 2-methyl-propan-2-vl (tf-butyl), cyclobutan-1-yl and the like.

[0063] "Alkenyl," by itself or as part of another substituent, refers to an unsaturated branched, straight-chain or cyclic alkyl radical having at least one carbon-carbon double bond derived by the removal of one hydrogen atom from a single carbon atom of a parent alkene. The group can be in either the cis or trans conformation about the double bond(s). Typical alkenyl groups include, but are not limited to, ethenyl; propenyls such as prop-1-en-l-yl, prop-l-en-2-yl, prop-2-eri-l-yl (allyl), prop-2-en-2-yl, cycloprop-1-en-l-yl; cycloprop-2-en-l-yl; butenyls such as but-1-en-l-yl, but-l-en-2-yl, 2-methyl-prop-l-en-l-yl, but-2-en-l-yl , but-2-en-l-yl, but-2-en-2-yl, buta-l,3-dien-l-yl, buta-l,3-dien-2-yl, cyclobut-1-en-l-yl, cyclobut-l-en-3-yl, cyclobuta-l,3-dien-.l-yl and the like.

[0064] "Alkynyl," by itself or as part of another substituent refers to an unsaturated branched, straight-chain or cyclic alkyl radical having at least one carbon-carbon triple bond derived by the removal of one hydrogen atom from a single carbon atom of a parent alkyne. Typical alkynyl groups include, but are not limited to, ethynyl; propynyls such as prop-1-yn-l-yl, prop-2-yn-l-yl, etc.; butynyls such as -but-1-yn-l-yl, but-l-yn-3-yl, but-3-yn-l-yl and the like.

[0065] "Alkoxy" by itself or as part of another substituent refers to a radical -OR³⁰ where R³⁰ is alkyl, substituted alkyl, heteroatkyl or substituted heteroalkyl, as defined herein. Representative examples include, but are not limited to, methoxy, ethoxy, propoxy, butoxy, cyclohexyloxy and the like.

[0066] "Alkoxycarbonyl," by itself or as part of another substituent, refers to a radical of the formula -C(O)-R³⁰, where R³⁰ is as defined above.

[0067] "Acyl" by itself or as part of another substituent refers to a radical -C(O)R³¹, where R³¹ is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroalkyl, substituted heteroalkyl, heteroarylalkyl or substituted heteroarylalkyl as defined herein. Representative examples include, but are not limited to formyl, acetyl, cyclohexylcarbonyl, cyclohexylmethylcarbonyl, benzoyl, benzylcarbonyl and the like.

[0068] "Aryl," by itself or as part of another substituent, refers to a monovalent aromatic hydrocarbon group derived by the removal of one hydrogen atom from a single carbon atom of a parent aromatic ring system, as defined herein. Typical aryl groups include, but are not limited to, groups derived from aceanthrylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, coronene, fluoranthene, fluorene, hexacene, hexaphene, hexalene, .w-indacene, s-indacene, indane, indene, naphthalene, octacene, octaphene, octalene, ovalene, penta-2,4-diene, pentacene, pentalene, pentaphene, perylene, phenalene, phenanthrene, picene, pleiadene, pyrene, pyranthrene, rubicene, triphenylene, trinaphthalene and the like. In some embodiments, an aryl group comprises from 6 to 20 carbon atoms (C₆-C₂₀ aryl). In other embodiments, an aryl group comprises from 6 to 15 carbon atoms (Cβ-Cis aryl). In still other embodiments, an aryl group comprises from 6 to 15 carbon atoms (Ce-Ci o aryl).

[0069] "Arylalkyl," by itself or as part of another substituent, refers to an acyclic alkyl group in which one of the hydrogen atoms bonded to a carbon atom;, typically a terminal or sp³ carbon atom, is replaced with an aryl group as, as defined herein. Typical arylalkyl groups include, but are not limited to, benzyl, 2-phenylethan-l-yl, 2-phenylethen-l-yl, naphthylmethyl, 2-naphthylethan-l-yl, 2-naphthylethen-l-yl, naphthobenzyl, 2-naphthophenylethan-l-yl and the like. Where specific alkyl moieties are intended, the nomenclature arylalkanyl, arylalkenyl and/or arylalkynyl is used. In some embodiments, an arylalkyl group is (C6-C₃₀) arylalkyl, e.g., the alkanyl, alkenyl or alkynyl moiety of the arylalkyl group is (C₁-C₁₀) alkyl and the aryl moiety is (C6-C20) aryl. In other embodiments, an arylalkyl group is (C6-C₂0) arylalkyl, e.g., the alkanyl, alkenyl or alkynyl moiety of the arylalkyl group is (Cj-Cβ) alkyl and the aryl moiety is (Ce-Ci 2) aryl. In still other embodiments, an arylalkyl group is (Cβ-Cis) arylalkyl, e.g., the alkanyl, alkenyl or alkynyl. moiety of the arylalkyl group is (C₁-C₅) alkyl and the aryl moiety is (Cβ-Cio) aryl.

[0070] "Aryloxycarbonyl," by itself or as part of another substituent, refers to a radical of the formula -C(O)-O-R³², where R³² is aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl.

[0071] "Aryloxy" by itself or as part of another substituent refers to a radical -OR³², where R³² is defined as above.

[0072] "Carbamoyl," by itself or as part of another substituent, refers to a radical of the formula -C(O)NR³³R³⁴, where R³³ and R³⁴ are independently selected from the group consisting of hydrogen, alkyl and alkoxy as defined herein, or alternatively, R³³ and R³⁴, taken together with the nitrogen atom to which they are attached, form a 4-, 5-, 6- or 7-membered cycloheteroalkyl ring as defined herein, which can optionally include from 1 to 4 of the same or different additional heteroatoms selected from the group consisting of O, S and N.

[0073] "Cycloalkyl," by itself or as part of another substituent, refers to a saturated or unsaturated cyclic alkyl radical, as defined herein. Where a specific level of saturation is intended, the nomenclature "cycloalkanyl" or "cycloalkenyl" is used. Typical cycloalkyl groups include, but are not limited to, groups derived from cyclopropane, cyclobutane, cyclopentane, cyclohexane, and the like. In some embodiments, the cycloalkyl group comprises from 3 to 10 ring atoms (C₃-C₁₀ cycloalkyl). In other embodiments, the^' cycloalkyl group comprises from 3 to 7 ring atoms (C₃-C₇ cycloalkyl).

[0074] "Cycloheteroalkyl," by itself or as part of another substituent, refers to a saturated or unsaturated cyclic alkyl radical in which one or more carbon atoms (and optionally any associated hydrogen atoms) are independently replaced with the same or different heteroatom. Typical heteroatoms to replace the carbon atom(s) include, but are not limited to, N, P, O, S, Si, etc. Where a specific level of saturation is intended, the nomenclature "cycloheteroalkanyl" or "cycloheteroalkenyl" is used. Typical cycloheteroalkyl groups include, but are not limited to, groups derived from epoxides, azirines, thiiranes, imidazolidine, morpholine, piperazine, piperidine, pyrazolidine, pyrrolidone, quinuclidine, and the like. In some embodiments, the cycloheteroalkyl group comprises from 3 to. 10 ring atoms (3-10 membered cycloheteroalkyl) In other embodiments, the cycloalkyl group comprise from 5 to 7 ring atoms (5-7 membered cycloheteroalkyl).

[0075] A cycloheteroalkyl group can be substituted at a heteroatom, for example, a nitrogen atom, with a (Ci-Cβ) alkyl group. As specific examples, N-methyl-imidazolidinyl, N-methyl-morpholinyl, N-methyl-piperazinyl,

N-methyl-piperidinyl, N-methyl-pyrazolidinyl and N-methyl-pyrrolidinyl are included within the definition of "cycloheteroalkyl." A cycloheteroalkyl group can be attached to the remainder of the molecule via a ring carbon atom or a ring heteroatom.

[0076] "Heteroalkyl," "Heteroalkanyl," "Heteroalkenyl" and "Heteroalkynyl," "by themselves or as part of other substituents, refer to alkyl, alkanyl, alkenyl and alkynyl groups, respectively, in which one or more of the carbon atoms (and optionally any associated hydrogen atoms), are each, independently of one another, replaced with the same or different heteroatoms or heteroatomic groups. Typical heteroatoms or heteroatomic groups which can replace the carbon atoms include, but are not limited to, O, S, N, Si, -NH-, -S(O)-, -S(O)₂-, -S(O)NH-, -S(O)₂NH- and the like and combinations thereof. The heteroatoms or heteroatomic groups can be placed at any interior position of the alkyl, alkenyl or alkynyl groups. Typical heteroatomic groups which can be included in these groups include, but are not limited to, -O-, -S-, -O-O-, -S-S-, -O-S-, -NR³⁵R³⁶-, =N-N=, -N=N-, -N=N-NR³⁷R³⁸, -PR³⁹-, -P(O)₂-, -POR⁴⁰^₅ -0-P(O)₂-, -SO-, -SO₂-, -SnR⁴¹R⁴²- and the like, where R³⁵, R³⁶, R³⁷, R³⁸, R³⁹, R⁴⁰, R⁴¹ and R⁴² are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl.

[0077] "Heteroaryl," by itself or as part of another substituent, refers to a monovalent heteroaromatϊc radical derived by the removal of one hydrogen atom from a single atom of a parent heteroaromatic ring systems, as defined herein. Typical heteroaryl groups include, but are not limited to, groups derived from acridine, D-carboline, chromane, chromene, cinnoline, fiiran, imidazole, indazole, indole, indoline, indolizϊne, isobenzofiiran, isochromene. isoindole, isoindoliπe, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, perimidine, phenanthridine, phenanthroline, phenazine, phthalazine, pteridine, purine, pyran, pyrazine, pyrazole, pyridazine, pyridine, pyrimϊdine, pyrrole, pyrrolizine, quinazoline, quinoline, quinolizine, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazole, xanthene, and the like. In some embodiments, the heteroaryl group comprises from 5 to 20 ring atoms (5-20 membered heteroaryl). In other embodiments, the heteroaryl group comprises from 5 to 10 ring atoms (5-10 membered heteroaryl). Exemplary heteroaryl groups include those derived from furan, thiophene, pyrrole, benzothiophene, benzofuran, benzimidazole, indole, pyridine, pyrazole, quinoline, imidazole, oxazole, isoxazole and pyrazine.

[0078] "Heteroarylalkyl" by itself or as part of another substituent refers to an acyclic alkyl group in which one of the hydrogen atoms bonded to a carbon atom, typically a terminal or sp³ carbon atom, is replaced with a heteroaryl group. Where specific alkyl moieties are intended, the nomenclature heteroarylalkanyl, heteroarylakenyl and/or heteroarylalkynyl is used. In some embodiments, the heteroarylalkyl group is a 6-21 membered heteroarylalkyl, e.g., the alkanyl, alkenyl or alkynyl moiety of the heteroarylalkyl is (Ci -Ce) alkyl and the heteroaryl moiety is a 5-15-membered heteroaryl. In other embodiments, the heteroarylalkyl is a 6-13 membered heteroarylalkyl, e.g., the alkanyl, alkenyl or alkynyl moiety is (C₁-C₃) alkyl and the heteroaryl moiety is a 5- 10 membered heteroaryl.

[0079] "Protecting group" refers to a grouping of atoms that when attached to a reactive functional group in a molecule masks, reduces or prevents reactivity of the functional group. Examples of protecting groups can be found in Greene et ah, "Protective Groups in Organic Chemistry", (Wiley, 4^th ed. 2006) and Harrison et ah, "Compendium of Synthetic Organic Methods", VoIs. 1-12 (John Wiley and Sons, 1971- 2007). ^•

[0080] "Substituted," when used to modify a specified group or radical, means that one or more hydrogen atoms of the specified group or radical are each, independently of one another, replaced with the same or different substituent(s). Substituent groups useful for substituting saturated carbon atoms in the specified group or radical include, but are not limited to -R^a, halo, -O^", =O, -OR^b, -SR^b, -S^", =S, -NR^CR^C, =NR^b, =N-OR^b, trihalomethyl, -CF₃, -CN, -OCN, -SCN, -NO, -NO₂, =N₂, -N₃, -S(O)₂R^b, -S(O)₂NR^b, -S(O)₂O^", -S(O)₂OR¹⁵, -OS(O)₂R", -OS(O)₂O^", -OS(O)₂OR^b, -P(O)(O^")₂, -P(O)(OR^b)(O ), -P(O)(OR^(OR*⁵), -C(O)R^b, -C(S)R^b, -C(NR¹OR¹³, -C(O)O^", -C(O)OR^b, -C(S)OR^b, -C(O)NR^CR^C, -C(NR¹ONR⁰R⁰, -OC(O)R^b, -OC(S)R^b, -OC(O)O^', -OC(O)OR^b, -OC(S)OR^b, -NR^bC(O)R^b, -NR^bC(S)R^b, -NR^bC(O)O^', -NR^bC(O)OR^b, -NR^bC(S)OR^b, -NR^bC(O)NR^cR^c, -NR^bC(NR^b)R^b and -NR¹³C(NR¹ONR⁰R⁰, where R^a is selected from the group consisting of alkyl, cycloalkyl, heteroalkyl, cycloheteroalkyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl; each R^b is independently hydrogen or R^a; and each R° is independently R^b or alternatively, the two R^cs are taken together with the nitrogen atom to which they are bonded form a 4-, 5-, 6- or 7-membered cycloheteroalkyl which can optionally include from 1 to 4 of the same or different additional heteroatoms selected from the group consisting of O, N and S. As specific examples, -NR^CR^C is meant to include -NH₂, -NH-alkyl, N-pyrrolidinyl and N-morpholinyl.

[0081] Similarly, substituent groups useful for substituting unsaturated carbon atoms in the specified group or radical include, but are not. limited to, -R^a, halo, -O^", -OR^b, -SR^b, -S^", -NR⁰R⁰, trihalomethyl, -CF₃, -CN, -OCN, -SCN, -NO, -NO₂, -N₃, -S(O)₂R^b, -S(O)₂O^", -S(O)₂OR^b, -OS(O)₂R^b, -OS(O)₂O^", -OS(O)₂OR^b, -P(O)(O^")₂, -P(O)(OR¹O(O-), -P(O)(OR^(OR¹⁵), -C(O)R^b, -C(S)R^b, -C(NR¹OR", -C(O)O^", -C(O)OR^b, -C(S)OR^b, -C(O)NR⁰R⁰, -C(NR¹^NR⁰R⁰, -OC(O)R^b, -OC(S)R^b, -OC(O)O^", -0C(0)0R^b, -OC(S)OR^b, -NR^bC(O)R^b, -NR^bC(S)R^b, -NR^bC(O)O^", -NR^bC(6)OR^b, -NR^bC(S)OR^b, -NR^bC(O)NR°R^c, -NR⁵C(NR¹OR¹⁵ and -NR¹⁵C(NR¹ONR⁰R⁰, where R^a, R^b and R^c are as previously defined. [0082] Substituent groups useful for substituting nitrogen atoms in heteroalkyl and cycloheteroalkyl groups include, but are not limited to, -R^a, -O^', -OR^b, -SR^b, -S^', -NR^CR^C, trihalomethyl, -CF₃, -CN, -NO, -NO₂, -S(O)₂R^b, -S(O)₂O-, -S(O)₂OR", -OS(O)₂R^b, -OS(O)₂O-, -OS(O)₂OR^b, -P(O)(O )₂, -P(O)(ORO(O ), -P(O)(OR^b)(OR^b), -C(O)R^b, -C(S)R^b, -C(NR^b)R^b, -C(O)OR^b, -C(S)OR^b, -C(O)NR^CR^C, -C(NR^NR⁰R⁰, -OC(O)R^b, -OC(S)R", -OC(O)OR^b, -OC(S)OR⁵, -NR^bC(O)R^b, -NR^bC(S)R^b, -NR^bC(O)OR^b, -NR^bC(S)OR^b, -NR^bC(O)NR^cR^c, -NR^bC(NR^b)R^b and -NR^bC(NR^b)NR^cR^c, where R^a, R^b and R^c are as previously defined.

[0083] Substituent groups from the above lists useful for substituting other specified groups or atoms will be apparent to those of skill in the art.

[0084] The substituents used to substitute a specified group can be further substituted, typically with one or more of the same or different groups selected from the various groups specified above.

[0085] "Salt" refers to a salt of a compound. Such salts include acid addition salts, formed with inorganic acids, including but not limited to hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, or phosphoric acid; or formed with organic acids including but not limited to acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl) benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1 ,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo[2.2.2]-oct-2-ene-l-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trϊmethylacetic acid, tertiary butylacetic acid, Iauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoϊc acid, salicylic acid, stearic acid, muconic acid, and the like; salts formed when an acidic proton present in the parent compound is replaced by a metal ion, e.g., an alkali metal ion, an alkaline earth ion, or an aluminum ion; an ammonium ion; or an organic base, including but not limited to ethanolamine, diethanolamine, triethanolamine, N-methylglucamine and the like; and zwitterionic salt compounds.

[0086] The following examples further illustrate the methods of the disclosure but, of course, should not be construed as in any way limiting their scope. EXAMPLE 1

[0087] This example demonstrates methods of preparing an α-bromo acid from an amino acid precursor.

[0088] To a stirred suspension of the amino acid [0.2 mM] in 1 mL of CH2CI2 was added a solution of isoamyl nitrite (1.1 equiv) and bromine (5 equiv) in 1.5 mL of CH2CI2. After complete dissolution of the amino acid, CH2CI2 was removed under reduced pressure. The remaining residue was suspended in EtOAc (10 mL) and washed with 5% aqueous hydrochloric acid (3 x 25 ml), followed by washes with water (3 x 25 ml). The desired product was extracted using aqueous sodium hydroxide (1 M), and then acidified with hydrochloric acid (2 M) until pH 2 and extracted with EtOAc (3 x 20 ml). The organic phase was dried (Na₂SO₄) and filtered, and the solvent was removed under reduced pressure to give the α-bromo acid.

EXAMPLE 2

[0089] This example demonstrates methods using aliphatic amines without aromatic substitution or acid substitution α to the amine.

[0090] 40 mg of 6-aminohexanoic acid was reacted under conditions set forth in Exmaple 1. The reaction was monitored by MS, and the identity of the product 6- bromohexanoic acid confirmed by NMR.

EXAMPLE 3

[0091] The following example explores reaction conditions and product distributions.

[0092] Under reaction conditions identical to those used with Br2 in Example 1, the reaction using I2 failed to produce the corresponding iodide. Using 10 equivalents of ICl however, as the source of halogen, results in the production of the chloride in good yield without the iodide. In a further experiment, using 10 equivalents of IBr, gives again the bromide with no detectable iodide. As per the postulated mechanism, the highly reactive nitryl, and nitrosyl halides are the active intermediates, neither of which is known for the iodide.

[0093] Conversion of 3-aminomethylpyridine to the bromide in THF was similar to that in CH₂Cl₂, but decreased in the series CH₂Cl₂ > CHCl₃ > CCl₄ with a corresponding increase in the formation of the hydroxy product. Reaction in DMF or DMSO led to remaining AMP under the conditions used and also favored the formation of the 3-(hydroxymethyl)pyridine over the bromide.

[0094] Using isoamyl nitrite as the nitroso source, and Br₂, in water, resulted in an incomplete conversion with very little of the hydroxy product. In all solvents tried using NaNC>₂ and acetic acid as the nitroso source, an increased amount of 3- (hydroxymethyl)pyridine was observed with incomplete reaction of the AMP. This latter observation is most likely due to the use of NaNO₂ for the nitroso source, as in CH2CI2, increasing additions of acetic acid up to 5 equivalents with respect to AMP, favored the formation of the bromide over the hydroxy product. The stronger acid TFA, however, favored the formation of the hydroxy product over the bromide. Addition of an organic base, TEA, piperidine or DBU was well tolerated up to about 1 equivalent with respect to AMP, with higher amounts leading to less conversion of the amine to the bromide. Reaction to the bromide was concentration dependent with best conversions occurring at > 0.1 molar in AMP (variable only explored in GH2CI2).

[0095] Conversion of 3-aminomethyl pyridine to 3-(bromomethyl)pyridine using 1.1 equiv. of nitrosyl agent and 5 equiv. of bromine was conducted in the solvent shown in Table 1 below. A sample of the reaction mixture was taken and quenched by high dilution into acetontrile for ESMS analysis of the products. 3- (hydroxymethyl)pyridine and 3-(isoamyloxymethyl)pyridine side products were also observed in addition to starting material and 3-(bromomethyl)pyridine product.

Table 1. Product distributions based on variation in reaction conditions.

[0096] The gas evolved by the reaction was identified by collecting the gas in an IR cell and examining by IR Spectroscopy. The IR spectrum in Figure 2 shows the N₂O gas produced by the reaction.

[0097] Conversion of 3-aminomethylpyridine (AMP) and 2-(2- aminoethyl)pyrϊdine (AEP) is efficient, as demonstrated by the HPLC traces before and after reaction as shown in Figure 3.

[0098] Titration of the addition of both isoamyl nitrite and Bτ₂ to AMP shows that the amine disappears from the reaction mixture on addition of one equivalent each of isoamyl nitrite and Br₂. As shown in Figure 7, the formation of the product 3- (bromomethyl)pyridine is out of phase with the disappearance of reacting amine, and in some trials was almost completely absent until greater than one equivalent of isoamyl nitrite and Br₂ was added. Best yields were obtained by a total addition of about five equivalents OfBr₂.in this example

EXAMPLE 4

[0099] The following example demonstrates the conversion of various amino acids to α-bromo acids.

[00100] Conversion of Ala, Cys(Trt), He, VaI: A small fraction of the amino acid was added to a solution of isoamyl nitrite (2 equiv.) and bromine (5 equiv.) in CH2CI2 (1 mL/mmol of amino acid), after the beginning of gas evolution the remaining amino acid (1 equiv.) is added gradually. Five minutes after complete dissolution of the amino acid, the reaction was stopped by removing the solvent under reduced pressure. The residue obtained was suspended in EtOAc (10 mL), and was washed with 5% HCl (3 x 2 ml) and water (3 x 25 ml). After washing, the desired product was extracted with aqueous IM NaOH, the aqueous solution was then acidified with 2M HCl until pH 2 and extracted with EtOAc (3 x 20 ml).

[00101] Conversion of Arg: A small fraction of the amino acid was added to a solution of isoamyl nitrite (2 equiv.) and bromine (5 equiv.) in CH₂CI₂ (1 mL/mmol of amino acid), after the beginning of gas evolution the remaining amino acid (1 equiv.) was added gradually. Five minutes after complete dissolution of the amino acid, the desired product was extracted with 1 M HCl (3 x 50 ml). The aqueous phases were combined and concentrated under reduced pressure. [00102] Conversion of Asp(OtBu), GIu(OtBu), Phe, His(Trt),

Lys(Boc), Leu, Met, Asn, GIn, Ser(tBu), Thr.(tBu), Trp(Boc), Tyr(tBu): A small fraction of the amino acid was added to a solution of isoamyl nitrite (2 equiv.) and bromine (5 equiv.) in CH2CI₂ (1 .mL/mmol of amino acid), after the beginning of gas evolution the rest of the amino acid (1 equiv.) was added gradually. Five minutes after the complete dissolution of the amino acid, the reaction was stopped by removing the solvent under reduced pressure. The residue obtained was suspended in EtOAc (10 mL), and was washed with 5% HCl (3 x 25 ml) and water (3 x 25 ml). After washing, the desired product was extracted with IM NaOH, the aqueous solution was then acidified with 2M HCI until pH 2 and extracted with EtOAc (3 x 20 ml). The organic phase was dried (Na₂SO₄) and filtered, and the solvent was removed under reduced pressure to give the corresponding α-bromo acid. The product was then purified by column chromatography on silica gel using hexane/ethyl acetate (7:3) as eluent.

[00103] Conversion of Phe, Leu, Arg, Ser(tBu), Tyr(tBu): A small fraction of the amino acid was added to a solution of isoamyl nitrite (2 equiv.) and bromine (5 equiv.) in CH₂Cb (1 mL/mmol of amino acid), after beginning of gas evolution the remaining amino acid (1 equiv.) is added gradually. Five minutes after complete dissolution of the amino acid the reaction was stopped by adding 50 ml of IM sodium sulfite / 1% HCl. This emulsion was stirred for 5 minutes until colorless. The organic phase was washed 2 more times with the same solution, then with water (30 ml). The organic phase was dried (Na₂SO₄) and filtered, and the solvent was removed under reduced. pressure to give the corresponding α-bromo acid.

[00104] Figures 4, 5, and 6 provide HPLC traces of α-bromoamino acids produced as described above.

EXAMPLE 5

[00105] The following example demonstrates the retention of stereochemistry.

[00106] Conversion of a chiral amine such as an α-amino acid to the α- bromo acid was achieved without inversion. Several amino acids were reacted under the conditions of 1.1 equivalents of isoamyl nitrite and 5 equivalents OfBr₂ in CH₂Cl₂. The optical rotary power shown in Table 2 below was measured at 589 nm on 20mg of α-bromo acid dissolved in 2 mL of methanol. Table 2. Product yields and optical rotations of α-bromo acids..

[00107] Conversion of a chiral amine without a neighboring group effect was demonstrated for (i?)-2-bromo-4-phenylbutane. (i?)-(-)-l-Methyl-3~ phenylpropylamine was reacted under the conditions of 1.1 equivalents of isoamyl nitrite and 5. equivalents of Br₂ in CH2CI2 to give (i?)-2-bromo-4-phenylbutane, as confirmed by ¹H NMR and HPLC-ESMS, and with retention of chirality as confirmed by [α]_D = 66.3°

EXAMPLE 6 [00108] The following example demonstrates the preparation of organic fluorides.

[00109] Conversion of a primary amine to the corresponding fluoride can be achieved by reacting the amine with the N-fluorinating reagent SELECTFLUOR^® in the presence OfNOBF₄.

EXAMPLE 7

[00110] The following example demonstrates the conversion of a series of amino acids to the corresponding α-bromo acids.

[0011 1] A mixture of isoamyl nitrite (2 equiv.) and bromine (5 equiv.) in

CH₂CI2 (1 mL/mmol of amino acid) was freshly prepared. To it was added a small portion of the solid amino acid (1 equiv.). After gas evolution begins, the remaining solid is added slowly to keep the reaction under control. After the amino acid has been added and dissolved, the reaction mixture in stirred for a further 5 minutes and then immediately concentrated under reduced pressure. The residue was dissolved in ethyl acetate (1 mL/mmol of amino acid) and was washed with 5% HCl (3 x 25 ml) and brine (3x 25ml). The organic phase was dried over Na₂SO₄ and the solvent was removed in vacuo. The residue was purified by silica chromatography eluting with 20% ethyl acetate / hexane.

[00112] As an alternative extraction workup, the residue was dissolved in ethyl acetate (1 mL/mmol of amino acid) and washed with 0.25M sodium sulfite, 1% HCl (3 x 30 ml), and brine (3 x 25ml). The organic phase was dried (Na₂SO^ and the solvent was removed in vacuo to give the α-bromo acid.

[00113] (25)-2-bromopropanoic acid. Z-Alanine (0.2 g, 2.24 mmol) was converted to (2S)-2-bromopropanoic acid (0.308g, 2.03 mmol) in 91% yield. ESMS m/z = 151/153 (M-H)^{" 1}HNMR (D₆-DMSO): δ 1.69 (d, 3H, 6.8 Hz₅ CH₃), 4.53 (q, IH, 6.8 Hz, CHBr). [α]²⁰D = -29.8° (1.0 MeOH), literature [α]²⁰ _D = -29.8° (1.0 MeOH). -

[00114] (2>S)-2-bromo-3-hydroxypropanoic acid. Z-Serine (0.105 g, 1 mmol) was converted to (2S)-2-bromo-3-hydroxypropionic acid (0.149 g, 0.88 mmol) in 89% yield. ESMS m/z = 167/169 (M-H)^". ¹H NMR (D₆-DMSO): δ 4.03 (t, IH, 6.8 Hz, CHBr), 4.24 (d, 2H, 7.3 Hz, CH₂). [α]²⁰ _D = -12.9° (1.0 MeOH), literature [α]²⁰ _D = -12.8° (1.0 MeOH).

[00115] (^S^-bromo-S-phenylpropanoic acid. Z-Phenylalanine (0.33g,

2mmol) was converted to (2S)-2-bromo-3-hydroxypropionic acid (0.394g, 1.73mmol) in 87% yield. ESMS m/z = 227/229 (M-H)^". ¹H NMR (D₆-DMSO): 8 3.16 (m, IH, CH₂Ph), 3.65 (m, IH, CH₂Ph), 4.63 (t, IH, 7.7 Hz, CHBr), 7.3 (m, 4H, ArH), 8.44 (s, IH, ArH). [Ct]²⁰D = -10.4° (1.0 MeOH), literature [<x]²⁰ _D = -10.2° (1.0 MeOH).

[00116] (2S)-2-bromo-4-methyIpentanoic acid. Z-Leucine (0.261 g,

2mmol) was converted to (2S)-2-bromo-4-methylpentanoic acid (0.338g, 1.74mmol) in 87% yield. ESMS m/z = 193/195 (M-H)^{" 1}H NMR (D₆-DMSO): δ 1.14 (d, 6H, 5.6 Hz, Me₂), 2.04 (q, IH, 6 Hz, CH₂), 2.20 (m, 1 H, CH(Me)₂), 4.3 (t, 1Η, 6.1 Hz, -CHBr). [Ot]²⁰D = -39.6° (1.0 MeOH), literature [α]²⁰ _D = -39.6° (1.0 MeOH).

[00117] (2_S)-2-bromo-3-methyIbutanoic acid. Z-Valine (0.234 g, 2 mmol) was converted to (2S)-2-bromo-3-methylbutanoic acid (0.34 g, 1.89 mmol) in 95% yield. ESMS m/z = 179/181 (M-H)^{" 1}H NMR (D₆-DMSO): δ 1.02 (d, 6H, 6.8 Hz, Me₂), 2.83 (m, IH, CHMe₂), 4.26 (d, 1Η, 4.9 Hz, CHBr). [α]²⁰ _D = -16.1° (1.0 MeOH), literature [α]²⁰ _D = -16.1° (1.0 MeOH).

[00118] As an alternate reaction, a mixture of isoamyl nitrite (2 equiv.) and bromine (5 equiv.) in CH₂Cl₂ (1 mL/mmol of amino acid), freshly prepared, was treated with a small portion of the solid amino acid Z-arginine (1 equiv.). After gas evolution begins, the remaining solid /,-arginine is added slowly to keep the reaction under control. After the amino acid has been added and dissolved, the reaction mixture in stirred for a further 5 minutes. The product was extracted with IM HCl (3x 50ml), and the aqueous layers concentrated under reduced. pressure to give the corresponding α- bromo acid in 97% yield.

[00119] Yields of several α-bromoacids from amino acids are shown in

Table 3.

Table 3. Summary of preparative scale conversions conducted at room temperature for the conversion of α-amino acids to α-bromo acids.

EXAMPLE 8

[00120] The following example demonstrates the conversion of an amine to the corresponding bromide.

[00121] . A mixture of isoamyl nitrite (1.1 equiv.) and bromine (5 equiv.) in CH2CI2 (1 mL/mmol of amine) was freshly prepared. To it was slowly added the amine (1 equiv.), with the evolution of gas keeping the reaction under control. The reaction mixture in stirred for- a further 5 minutes and then immediately concentrated under reduced pressure. The residue was dissolved in ethyl acetate and was washed with 5% HCl (3x) and brine (3x). The organic phase was dried over Na₂SO₄ and the solvent was removed in vacuo. The residue was purified as necessary by silica chromatography.

[00122] 2-(2~bromoethyl)pyridine. ESMS m/z = 186/188 (MH)⁺. ¹H

NMR (D₆-DMSO): δ 3.61 (t, 2H₅ 6.3 Hz, CH₂Pyr), 3.95 (t, 2H, 6.4 Hz, CH₂Br), 7.98 (t, IH, 6.4 Hz, rø-PyrH), 8.08 (d, IH, 7.08 Hz, /w-PyrH), 8.59 (t, IH, 7.6 Hz, />-PyrH), 8.9 (d, IH, 5.4 Hz, σ-PyrH).

[00123] 3-(bromomethyI)pyridine. ESMS m/z = 172/174 (MH)⁺. ¹H

NMR (D₆-DMSO): δ 4.87 (s, 2H, CH₂Br), 8.10 (dd, IH, 5.8 Hz, /w-PyrH), 8.69 (dt, IH, 6 Hz,/7-PyrH), 8.89 (d, IH, 5.8 Hz, o-PyrH), 9.07 (d, IH, ø-PyrH).

[00124] 6-bromohexanoic acid. ESMS m/z = 193/195 (M-H)^".

EXAMPLE 9

[00125] The following example demonstrates the conversion of a primary amine to an organic alcohol.

[00126] To a suspension of amine (1 equiv.) in CH₂Cl₂ (0.8ml/mmol), N- bromosuccinimide (2.05 equiv.,) was added followed by a few drops of DMF to ensure complete dissolution. A 2.8M solution of trifluoroacetic acid (5 equiv.) in CH₂Cl₂ was added to sodium nitrite (5 equiv) to generate a solution of nitrous acid. The nitrous acid solution was slowly added to the amine mixture, and stirred at room temperature for 10 minutes. The reaction was concentrated in vacuo, and the residue redissolved in ethyl acetate (2ml/mmol). The organic phase was washed with 2M HCl (3x), and brine (3x). The organic phase was dried over Na₂SO₄ and the solvent was removed in vacuo to give the corresponding hydroxy product.

[00127] (2-S)-2-hydroxy-3-phenyIpropanoic acid. Z-Phenylalanine (6 g,

36.4 mmol) was converted to (2S)-2-hydroxy-3-phenylpropionic acid (5.01 g) in 83% yield. RP-HPLC (Ci₈ anal.) - ESMS m/z = 165 (M-H)^". The gas evolved during the reaction was identified by collecting the gas in an IR cell and examining by IR Spectroscopy. The IR spectrum was identical to that of the N₂O collected previously in Figure 2. [00128] In addition, the amino acids His(Trt), Ser(tBu), LysQBoc),

GIu(OtBu), Arg, Asn and Tyr(tBu) were converted by the same procedure to the corresponding α-hydroxy acids and confirmed by RP-HPLC-ESMS.

[00129] 3-(hydroxymethyl)pyridine. From 3-aminomethylpyridine.

ESMS m/z = 110 (MH)⁺.

[00130] 2-(2-hydroxyethyI)pyridine. From 2-(2-aminoethyl)pyridine.

ESMS m/z = 124 (MH)⁺.

[00131] 6-hydroxyhexanoic acid. From 6-hydroxyhexanoic acid. ESMS m/z = 131 (M-H)^".

EXAMPLE 10

[00132] The following example demonstrates the preparation of a α- hydroxy acid derivative.

[00133] To a suspension of α-amino Weinreb amide (1 equiv.) in CH₂CI2

(0.8ml/mmol) is added N-bromosuccinimide (2.05 equiv.). A 2.8M solution of trifluoroacetic acid (5 equiv.) in CH₂Cl₂ is added to sodium nitrite (5 equiv.) to generate a solution of nitrous acid. The nitrous acid solution is slowly added to the phenylalanine mixture, and stirred at room temperature for 10 minutes.

[00134] The isolated α-hydroxy Weinreb amide is protected with

TBDMSCl, and then reduced with LiAlH₄ to give the TBDMS protected α-hydroxy aldehyde.

[00135] It should be understood that various changes and modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present subject matter and without diminishing its intended advantages. It is therefore intended that such changes and modifications be covered by the appended claims.

Claims

WHAT IS CLAIMED IS:

1. A method for preparing an organic compound, comprising reacting a primary amine with an activating agent and a nitrosyl agent to produce an organic compound and nitrous oxide.

2. The method of Claim 1, wherein the organic compound is an organic alcohol or organic halide.

3. The method of Claim I₃ wherein the organic compound is an organic alcohol.

4. The method of Claim 1, wherein the organic compound is an organic halide.

5. The method of Claim 1, where the organic compound is an organic bromide, organic chloride or organic fluoride.

6. The method of Claim 1, wherein the organic compound is an organic bromide.

7. The method of Claim 1, wherein the organic compound is an organic halide and the activating agent is an alkyl nitrite and X₂, XNO₂, HOX, an alkyl hypohalite, cyanogen bromide, NO₂-BX₄ and X2, N-halosuccinimide, 1- (chloromethyl)-4-fluoro-l,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate), or cyanuric halide, wherein X is F, Cl, Br, or I.

8. The method of Claim 1, wherein the organic compound is an organic halide and the activating agent is N-bromosuccinimide.

9. The method of Claim 1, wherein the organic compound is an organic halide and the activating agent is BrNO₂ or isoamyl nitrite and Br₂.

10. The method of Claim 1, wherein the organic compound is an organic halide and the nitrosyl agent is XNO, NO-BX₄ and X₂, HONO and X₂, NaNO₂ and trifluoroacetic acid and X₂, NaNO₂ and acetic acid and X₂, Na₂Fe(CN)₅(NO) and X₂, cyanuric halide and NO-BX4, or a nitrite and an acid and X₂, wherein X is Br, Cl or F.

11. The method of Claim 1, wherein the organic compound is an organic halide and the nitrosyl agent is BrNO.

12. The method of Claim 1, wherein the organic compound is an organic halide and the nitrosyl agent is sodium nitrite and trifluoroacetic acid and Br₂.

13. The method of Claim 1, wherein the organic compound is an organic halide and the activating agent is N-bromosuccinimide and the nitrosyl agent is BrNO.

14. The method of Claim 1, wherein the organic compound is an organic halide and the activating agent is N-bromosuccinimide and the nitrosyl agent is HONO and Br₂.

15. The method of Claim 1, wherein the organic compound is an organic halide and the activating agent is N-bromosuccinimide and the nitrosyl agent is NaNθ2 and trifluoroacetic acid and Br₂.

16. The method of Claim 1, wherein the organic compound is an organic halide and the activating agent is isoamyl nitrite and Br2 and the nitrosyl agent is BrNO.

17. The method of Claim 1, wherein the organic compound is an organic halide and the activating agent and nitrosyl agent are generated by the combination of alkyl nitrite, X₂, and primary amine, wherein X is F, Cl, Br, or I.

18. The method of Claim 1, wherein the organic compound is an organic halide and the activating agent is isoamyl nitrite and Br₂ and the nitrosyl agent is HONO and Br₂.

19. The method of Claim 1, wherein the organic compound is an organic halide and the activating agent is isoamyl nitrite. and Br₂ and the nitrosyl agent is NaNO₂ and trifluoroacetic acid and Br₂.

20. The method of Claim 1, wherein the organic compound is an organic halide and the activating agent is cyanuric chloride and the nitrosyl agent is NO- BF4 and cyanuric chloride.

21. The method of Claim 1, wherein the organic compound is an organic halide and the activating agent is cyanuric chloride and the nitrosyl agent is ClNO.

22. The method of Claim 1, wherein the organic compound is an organic halide and the activating agent is cyanuric fluoride and the nitrosyl agent is ^"NO-BF₄ and cyanuric fluoride.

23. . The method of Claim 1, wherein the organic compound is an organic halide and the activating agent is cyanuric fluoride and the nitrosyl agent is FNO.

24. The method of Claim 1, wherein the organic compound is an organic halide and the activating agent is cyanuric bromide and the nitrosyl agent is NO- BF₄ and cyanuric bromide.

25. The method of Claim 1, wherein the organic compound is an organic halide and the activating agent is cyanuric bromide and the nitrosyl agent is BrNO.

26. The method of Claim 1, wherein the organic compound is an organic halide and the primary amine is contacted with the activating agent and nitrosyl agent at between about -78 ⁰C and about 200 ⁰C.

27. The method of Claim 1, wherein the organic compound is an organic halide and the primary amine is contacted with the activating agent and nitrosyl agent at between about -50 ⁰C and about 50 ⁰C.

28. The method of Claim 1, wherein the organic compound is an organic halide and the primary amine is contacted with the activating agent and nitrosyl agent at between about 15 ⁰C and about 30 ⁰C.

29. The method of Claim 1, wherein the organic compound is an organic halide and the ratio of primary amine, activating agent and nitrosyl reagent is about 1:0.1:0.1 to about 1:10:100.

30. The method of Claim 1, wherein the organic compound is an organic halide and the ratio of primary amine, activating agent and nitrosyl reagent is about 1 :1 :1 to about 1:5:10.

31. The method of Claim 1, wherein the organic compound is an organic halide and the ratio of primary amine, activating agent and nitrosyl reagent is about 1:2:3.

32. The method of Claim 1, wherein the organic compound is an organic halide and the primary amine is at least partially dissolved in a solvent.

33. The method of Claim 1, wherein the organic compound is an organic halide and the primary amine is at least partially dissolved in a solvent selected from the group of solvents consisting of tetrahydrofuran, dichloromethane, chloroform, carbon tetrachloride, dimethyl formamϊde, dimethyl sulfoxide, t- butanol, diethylether, acetic acid, hexane, dichloroethane, ethyl acetate, acetonitrile, methanol, ethanol, bromine and water.

34. The method of Claim 1, wherein the organic compound is an organic halide and the primary amine is at least partially dissolved in tetrahydrofuran or dichloromethane.

35. The method of Claim 1, wherein the organic compound is an organic halide and the primary amine is at least partially dissolved in a solvent and the amine is an α-amino acid, β-amino acid, α-amino amide, β-amino amide, α- amino ester, β-amino ester, α-amino aldehyde, β-amino aldehyde, β-amino ether, a β-amino alcohol, γ-amino ether, or a γ-amino alcohol.

36. The method of Claim 1, wherein the organic compound is an organic halide, the primary amine is at least partially dissolved in a solvent and the amine is an α-L-amino acid.

37. The method of Claim 1, wherein the organic compound is an organic halide, the primary amine is at least partially dissolved in a solvent and the amine is an α-D-amino acid.

38. The method of Claim 1, wherein the organic compound is an organic halide, the primary amine is an α-amino acid at least partially dissolved in methylene chloride or tetrahydrofuran, the activating agent is isoamyl nitrite and Br2 and the nitrosyl agent is BrNO and the amine is contacted with the' activating agent and nitrosyl agent at about 25 ⁰C.

39. The method of Claim 1, wherein the organic compound is an organic halide, the primary amine is at least partially dissolved in a solvent and the amine is an α-amino acid, the solvent is methylene chloride or tetrahydrofuran, the activating agent is isoamyl nitrite and Br₂ and the nitrosyl agent is isoamyl nitrite and Br2 and the amine is contacted with the activating agent and nitrosyl agent at about 25 ⁰C.

40. The method of Claim 1, wherein the organic compound is an organic halide, the primary amine is at least partially dissolved in a solvent and the amine is an α-amino acid, the solvent is methylene chloride or tetrahydrofuran, the activating agent is N-bromosuccinimide and the nitrosyl agent is BrNO and the amine is contacted with the activating agent and nitrosyl agent at about 25 ⁰C.

41. The method of Claim 1, wherein the organic compound is an organic halide, the primary amine is at least partially dissolved in a solvent and the amine is an α-amino acid, the solvent is methylene chloride or tetrahydrofuran, the activating agent is N-bromosuccinimide and the nitrosyl agent is NaNθ2 and trifluoroacetic acid and Efø, and the amine is contacted with the activating agent and nitrosyl agent at about 25 ⁰C.

42. The method of Claim 1, wherein the organic compound is an organic alcohol and the activating agent is an alkyl nitrite and X₂, XNO₂, HOX₅ an alkyl hypohalite, cyanogen bromide, NO₂-BX₄ and X₂, N-halosuccinimide, 1- (chloromethyl)-4-fluoro-l,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) or cyanuric halide, wherein X is fluoride, chloride, bromide or iodide.

43. The method of Claim 1, wherein the organic compound is an organic alcohol and the activating agent is N-bromosuccinimide.

44. The method of Claim 1, wherein the organic compound is an organic alcohol and the activating agent is BrNO₂ or isoamyl nitrite and Br₂.

45. The method of Claim 1, wherein the organic compound is an organic alcohol ^■ and the nitrosyl agent is NO2-BX4 and trifluoroacetic acid, HONO, NaNO₂ and trifluoroacetic acid, NaNO₂ and acetic acid, or a nitrite and an acid, wherein X is Br, Cl or F.

46. The method of Claim 1, wherein the organic compound is an organic alcohol and the nitrosyl agent is HONO.

47. The method of Claim 1, wherein the organic compound is an organic alcohol and the nitrosyl agent is sodium nitrite and trifluoroacetic acid.

48. The method of Claim 1, wherein the organic compound is an organic alcohol and the activating agent is N-bromosuccinimide and the nitrosyl agent is HONO.

49. The method of Claim I₅ wherein the organic compound is an organic alcohol and the activating agent is N-bromosuccinimide and the nitrosyl agent is sodium nitrite and trifluoroacetic acid.

50. The method of Claim 1, wherein the organic compound is an organic alcohol and the activating agent is cyanuric bromide and the nitrosyl agent is HONO.

51. The method of Claim 1, wherein the organic compound is an organic alcohol and the activating agent is cyanuric bromide and the nitrosyl agent is sodium nitrite and trifluoroacetic acid.

52. The method of Claim 1, wherein the organic compound is an organic alcohol • and the amine is contacted with the activating agent and nitrosyl agent at between about -78 °C and about 200 ⁰C.

53. The method of Claim 1, wherein the organic compound is an organic alcohol and the amine is contacted with the activating agent and nitrosyl agent at between about -50 ⁰C and about 50 ⁰C.

54. The method of Claim 1, wherein the organic compound is an organic alcohol and the amine is contacted with the activating agent and nitrosyl agent at about 25 ⁰C.

55. The method of Claim 1, wherein the organic compound is an organic alcohol and the ratio of amine, activating agent and nitrosyl reagent is about 1:0.1 :0.1 to about 1:10:100.

56. The method of Claim 1, wherein the organic compound is an organic alcohol and the ratio of amine, activating agent and nitrosyl reagent is about 1:1:1 to about 1:5:10.

57. The method of Claim 1, wherein the organic compound is an organic alcohol and the ratio of amine, activating agent and nitrosyl reagent is about 1 :2:3.

58. The method of Claim 1, wherein the organic compound is an organic alcohol and the primary amine is at least partially dissolved in a solvent.

59. The method of Claim 1, wherein the organic compound is an organic alcohol and the primary amine is at least partially dissolved in a solvent and the solvent is tetrahydrofuran, dichloromethane, chloroform, carbon tetrachloride, dimethyl formamide, dimethyl sulfoxide, /-butanol, diethylether, acetic acid, hexane, dichloroethane. ethyl acetate, acetonitrile, methanol, ethanol, bromine or water.

60. The method of Claim 1, wherein the organic compound is an organic alcohol and the primary amine is at least partially dissolved in tetrahydrofuran or dichloromethane.

61. The method of Claim 1, wherein the organic compound is an organic alcohol and the carbon atom to which the amine is attached is chiral and the chirality is substantially retained in the organic alcohol.

62. The method of Claim 1, wherein the organic compound is an organic alcohol and the primary amine is an α-amino acid, β-amino acid, α-amino amide, β- amino amide, α-amino ester, β-amino ester, α-amino aldehyde, β-amino aldehyde, β-amino ether, a β-amino alcohol, γ-amino ether, or a γ -amino alcohol.

63. The method of Claim 1, wherein the organic compound is an organic alcohol and the amine is an α-amino acid.

64. The method of Claim 1, wherein the organic compound is an organic alcohol and the amine is an α-L-amino acid.

65. The method of Claim 1, wherein the organic compound is an organic alcohol and the amine is an α-D-amino acid.

66. The method of Claim 1, wherein the organic compound is an organic alcohol and the primary amine is at least partially dissolved in methylene chloride or tetrahydrofuran, the activating agent is N-bromosuccinimide and the nitrosyl agent is HONO and the amine is contacted with the activating agent and nitrosyl agent at about 25 ⁰C. •

67. The method of Claim 1, wherein the organic compound is an organic alcohol and wherein the primary amine is an α-amino acid and is at least partially dissolved in acetonitrile, the activating agent is N-bromosuccinimide and the nitrosyl agent is HONO and the amine is contacted with the activating agent and nitrosyl agent at about 25 ⁰C.

68. The method of Claim 1, wherein the organic compound is an organic alcohol and wherein the primary amine is an α-amino acid and is at least partially dissolved in methylene chloride or tetrahydrofuran, the activating agent is N- bromosuccinimide and the nitrosyl agent is sodium nitrite and trifluoroacetic acid and the amine is contacted with the activating agent and nitrosyl agent at about 25 ⁰C.

69. The method of Claim 1, wherein the organic compound is an organic alcohol and wherein the primary amine is an α-amiπo acid and is at least partially dissolved in acetonitrile, the activating agent is N-bromosuccinimide and the nitrosyl agent is NaNO₂ and trifluoroacetic acid, and the amine is contacted with the activating agent and nitrosyl agent at about 25 ⁰C.

70. The method according to Claim 1, wherein the primary amine is described by Formula (I) and the organic compound is described by Formula (IT),

0) (^Q) wherein:

Y is OH, Br, Cl or F;

R¹, R², R³ are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, acyl, substituted acyl, alkoxycarbonyl, substituted alkoxycarbonyl, aryloxycarbonyl, substituted aryloxycarbonyl, carbamoyl, substituted carbamoyl, carboxyl, nitro, cyano, or optionally R¹ and R² together with the carbon atom to which they are attached form a cycloalkyl, substituted cycloalkyl, cycloheteroalkyl or substituted cycloheteroalkyl ring.

71. The method of Claim 70, wherein R¹ is hydrogen and R² is acyl, substituted acyl, alkoxycarbonyl, substituted alkoxycarbonyl, aryloxycarbonyl, substituted aryloxycarbonyl, carboxyl, carbamoyl, substituted carbamoyl, carboxyl, nitro or cyano.

72. The method of Claim 70, wherein R¹ is hydrogen, R² is carboxyl, carbamoyl or substituted carbamoyl and R³ is hydrogen, alkyl, substituted alkyl, arylalkyl, substituted arylalkyl, heteroalkyl, substituted heteroalkyl, heteroarylalkyl or substituted heteroarylalkyl.

73. The method of Claim 70, wherein R¹ is hydrogen, R² is carboxyl, carbamoyl or substituted carbamoyl and wherein R³ is independently hydrogen or alkyl.

74. The method of Claim 70, wherein R¹ is hydrogen, R² is carboxyl, carbamoyl or substituted carbamoyl and wherein R³ is independently hydrogen, methyl, isopropyl, isobutyl, sec-butyl, /-butyl, cyclopentyl or cyclohexyl.

75. The method of Claim 70, wherein R¹ is hydrogen, R² is carboxyl, carbamoyl or substituted carbamoyl and wherein R³ is substituted alkyl.

76. The method of Claim 70, wherein R¹ is hydrogen, R² is carboxyl, carbamoyl or substituted carbamoyl and wherein R³ is -CH₂OH, -CH(OH)CH₃, -CH₂CO₂H, -CH₂CH₂CO₂H, -CH₂CONH₂, -CH₂CH₂CONH₂, -CH₂CH₂SCH₃, -CH₂SH, -CH₂(CH₂J₃NH₂ or -CH₂CH₂CH₂NHC(NH)NH₂.

77. The method of Claim 70, wherein R¹ is hydrogen, R² is carboxyl, carbamoyl or substituted carbamoyl and wherein R³ is aryl, arylalkyl, substituted arylalkyl or heteroarylalkyl.

78. The method of Claim 70, wherein R¹ is hydrogen, R² is carboxyl, carbamoyl or substituted carbamoyl and wherein R³ is phenyl, benzyl, 4-hydroxybenzyl, 4-imidazolylmethyl or 3-indolylmethyl

79. The method of Claim 70, wherein R¹ is hydrogen, R² is carboxyl, carbamoyl or substituted carbamoyl and R³ contains one or more functional groups that are independently attached to protecting groups.

80. The method of Claim 70, wherein R¹ is hydrogen, R² is carboxyl, carbamoyl or substituted carbamoyl and R³ contains one or more -OH groups that are independently protected as -O-t-butyl, OBzI, -OAc, -OTrityl, or protecting groups commonly used for Ser, Thr, Tyr amino acid sidechains.

81. The method of Claim 70, wherein R¹ is hydrogen, R² is carboxyl, carbamoyl or substituted carbamoyl and R³ contains one or more -NH₂ groups that are independently protected as -NHBoc, -NHBzI, -N(BzI)₂, -N(BzI)BoC, - NHAc, -NHCbz, -NH(2-CI-Cbz), -N(Me)₂, -NHCOCF₃, -NHFmoc, - _. NHDde, NHTrityl, NHMtt, or protecting groups commonly used for Lys or Orn amino acid sidechains.

82. The method of Claim 70, wherein R¹Ms hydrogen, R² is carboxyl, carbamoyl or substituted carbamoyl and R³ contains one or more -NH- groups that are independently protected as -N(Boc)-, -N(Bom)-, -N(Tosyl)-, -N(Trityl)-, or protecting groups commonly used for His and Trp amino acid sidechains.

83. The method of Claim 70, wherein R¹ is hydrogen, R² is carboxyl, carbamoyl or substituted carbamoyl and R³ contains one or more -SH groups that are independently protected as — SBzI, STrityl, -SMtt. or protecting groups commonly used for Cys amino acid sidechains.

84. The method of Claim 70, wherein R¹ is hydrogen, R² is carboxyl, carbamoyl or substituted carbamoyl and R³ contains one or more -COOH group that are independently protected as -COO-t-butyl, -COOBzI, -COOAllyl, COODmab, or protecting groups commonly used for Asp or GIu amino acid sidechains.

85. The method of Claim 70, wherein R¹ is hydrogen, R² is carboxyl, carbamoyl or substituted carbamoyl and R³ contains one or more — CONH₂, - NHC(=NH)NH₂ group that are independently protected as protecting groups commonly used for Asn, GIn or Arg amino acid sidechains.

86. The method of Claim 70, wherein the compound of Formula (I) is the L stereoisomer.

87. The method of Claim 70, wherein the stereochemistry of the compound of Formula (I) is retained in the compound of Formula (II).

88. The method of Claim 70, wherein the compound of Formula (I) is the D stereoisomer.

89. The method of Claim 70, wherein the stereochemistry of the compound of Formula (I) is retained in the compound of Formula (II).

90. The method of Claim 70, wherein the activating agent is an alkyl nitrite and X₂, XNO₂, HOX, an alkyl hypohalite, cyanogen bromide, NO2-BX4 and X₂,

N-halosuccϊnimide, l-(chloromethyl)-4-fluoro-l,4- diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate), or cyanuric halide, wherein X is F₅ Cl, Br, or I.

91. The method of Claim 70, wherein, when Y=Br, Cl or F, the nitrosyl agent is XNO, NO-BX₄ and X₂, HONO and X₂, NaNO₂ and trifluoroacetic acid and X₂, NaNO₂ and acetic acid and X₂, Na₂Fe(CN)₅(NO) and X₂, cyanuric halide and NO-BX₄, or a nitrite and an acid and X2, wherein X is Br, Cl or F.

92. The method of Claim 70, wherein when Y=Cl, Br or F, the activating agent and nitrosyl agent are generated by the combination of alkyl nitrite, X2, and primary amine, wherein X is F, Cl, Br, or I.

93. The method of Claim 70, wherein when Y is Cl, Br or F, the activating agent and nitrosyl agent are generated by the combination of isoamyl nitrite, Br₂, and primary amine.

94. The method of Claim 70, wherein, when Y=OH, the nitrosyl agent is NO₂- BX4 and trifluoroacetic acid, HONO, NaNθ₂ and trifluoroacetic acid, NaNO₂ and acetic acid, or a nitrite and an acid, wherein X is Br, Cl or F.

95. The method of Claim 70, wherein the conversion occurs between about 10 ⁰C and about 40⁰C.

96. The method of Claim 70, wherein the conversion is conducted at room temperature.

97. The method of Claim 70, wherein the conversion occurs with greater than 90% retention of stereochemistry.

98. The method of Claim 70, wherein the conversion occurs with greater than 95% retention of stereochemistry.

99. The method of Claim 70, wherein the conversion occurs with complete retention of stereochemistry.

100. A method for preparing an α-hydroxy acid or derivative thereof, comprising treating a α-amino acid or derivative thereof with a activating agent and a nitrosyl agent, with resulting generation of nitrous oxide.

101. The method of Claim 100, wherein the α-hydroxy acid derivative is an α- ^• hydroxy ester, α-hydroxy aldehyde or α-hydroxy alcohol, and orthogonally protected α-hydroxy esters, α-hydroxy aldehydes or α-hydroxy alcohols.

102. The method according to Claim 100, wherein the α-hydroxy acid derivative is a hydroxyl-protected α-hydroxy aldehyde.

103. The method of Claim 100, wherein the α-hydroxy acid derivative is a hydroxyl-protected α-hydroxy aldehyde and the hydroxyl-protecting group is an ester or an ether.

104. The method of Claim 100, wherein the α-hydroxy acid derivative is a hydroxyl-protected α-hydroxy aldehyde and the hydroxyl-protecting group is a silyl ether protecting group.

105. The method of Claim 100, wherein the α-hydroxy acid derivative is a hydroxyl-protected α-hydroxy aldehyde and the hydroxyl-protecting group is a tert-butyldimethylsilyl group.

106. The method of Claim 100, comprising treating an α-amino acid with a activating agent and a nitrosyl agent to produce the α-hydroxy acid or its derivative, and subsequently reducing the acid or its derivative to an α- hydroxy aldehyde.

107. The method of Claim 100, wherein the α-amino acid derivative is an α-amino Weinreb amide, and the α-amino Weinreb amide is converted to the α- hydroxy Weinreb amide, and subsequently reduced to the aldehye.

108. The method of Claim 100, wherein the conversion occurs with greater than 90% retention of stereochemistry.

109. The method of Claim 100, wherein the conversion occurs with greater than 95% retention of stereochemistry.

110. The method of Claim 100, wherein the conversion occurs with complete retention of stereochemistry.

111. The method of Claim 100, wherein the activating agent is an alkyl nitrite and X₂, XNO₂, HOX, an alkyl hypohalite, cyanogen bromide, NO₂-BX₄ and X2, N-halosύccinimide, l-(chloromethyl)-4-fluoro-l,4_r diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate), or cyanuric halide, wherein X is F, Cl, Br₅ or I.

112. The method of Claim 100, wherein the nitrosyl agent is NO₂-BX₄ and trifluoroacetic acid, HONO, NaNθ2 and trifluoroacetϊc acid, NaNθ2 and acetic acid, or a nitrite and an acid, wherein X is Br, Cl or F.

113. - The method according to Claim 1 , wherein the reaction is conducted between about 10 ⁰C and about 40⁰C.

114. The method of Claim 1, wherein the reaction is conducted at about room temperature.

115. The method of Claim 1, wherein the reaction is conducted between about 10 ⁰C and about 40 ⁰C and the yield of the organic alcohol or organic halide is greater than 50%.

116. The method of Claim 1, wherein the reaction is conducted between about 10 ⁰C and about 40 ⁰C and the yield of the organic alcohol or organic halide is greater than 75%.

117. The method of Claim 1, wherein the reaction is conducted between about 10 ⁰C and about 40 ⁰C and the yield of the organic alcohol or organic halide is greater than 90%.

118. The method of Claim 1, wherein the reaction is conducted between about 10 ⁰C and about 40 ⁰C with greater than 90% retention of stereochemistry.

119. The method of Claim 1, wherein the reaction is conducted between about 10 ⁰C and about 40 ⁰C with greater than 95% retention of stereochemistry.

120. The method of Claim 1, wherein the reaction is conducted between about 10 ⁰C and about 40 ⁰C and the conversion occurs with complete retention of stereochemistry.

121. The method of Claim 1, wherein the reaction is conducted between about 10 ⁰C and about 40⁰C and the conversion is conducted on multigram scale.

122. The method of Claim 1, wherein the reaction is conducted between about 10 ⁰C and about 40 ⁰C with greater than about 10 grams of the primary amine.

123. The method of Claim 1, wherein the reaction is conducted between about 10 ⁰C and about 40 ⁰C with greater than about 100 grams of the primary amine.

124. The method of Claim 1, wherein the reaction is conducted between about 10 °C and about 40⁰C with greater than about 1 kilogram of the primary amine.

125. The method of any of claims 122-124, wherein the conversion is conducted at room temperature.

127. A method for preparing an organic compound, comprising treating a primary organic N-haloamine or N,N-dihaloamine with a nitrosyl agent to produce the organic compound and nitrous oxide.

128. The method of Claim 127, wherein the primary organic N,N-dihaloamine is an N, N-dibromoamine.

129. The method of Claim 127, wherein the organic compound is an organic alcohol or organic haiide.

130. The method of Claim 127, wherein the organic compound is an organic alcohol. ^r

131. The method of Claim 127, wherein the organic compound is an organic haiide.

132. The method of Claim 127, wherein the organic compound is an organic bromide, organic chloride or organic fluoride.

133. The method of Claim 127, wherein the organic compound is an organic bromide.

134. The method of Claim 127, wherein the organic compound is an organic haiide and the nitrosyl agent is XNO₅ NO-BX₄ and X₂, HONO and X₂, NaNO₂ and trifluoroacetic acid and X₂, NaNO₂ and acetic acid and X₂, Na₂Fe(CN)S(NO) and X₂, cyanuric haiide and NO-BX₄, or a nitrite and an acid and X₂, wherein X is Br, Cl or F.

135. The method of Claim 127, wherein the organic compound is an organic haiide and the nitrosyl agent is BrNO.

136. The method of Claim 127, wherein the organic compound is an organic haiide and the nitrosyl agent is isoamyl nitrite and Br₂.

137. The method of Claim 127, wherein the organic compound is an organic halide and the nitrosyl agent is sodium nitrite and trifluoroacetic acid and Br₂

138. The method of Claim 127, wherein the organic compound is an organic alcohol and the nitrosyl agent is NO₂-BX₄ and trifluoroacetic acid, HONO, NaNO₂ and trifluoroacetic acid, NaNθ2 and acetic acid, or a nitrite and an acid, wherein X is Br, Cl or F.

139. The method of Claim 127, wherein the organic compound is an organic alcohol and the nitrosyl agent is HONO.

140. The method of Claim 127, wherein the organic compound is an organic alcohol and the nitrosyl agent is sodium nitrite and trifluoroacetic acid.