WO2008054155A1 - Method for the preparation of optically active 2-sulfonyloxy-1-phenylethanol derivatives - Google Patents

Method for the preparation of optically active 2-sulfonyloxy-1-phenylethanol derivatives Download PDF

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WO2008054155A1
WO2008054155A1 PCT/KR2007/005492 KR2007005492W WO2008054155A1 WO 2008054155 A1 WO2008054155 A1 WO 2008054155A1 KR 2007005492 W KR2007005492 W KR 2007005492W WO 2008054155 A1 WO2008054155 A1 WO 2008054155A1
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Kee-In Lee
Do-Min Lee
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Korea Research Institute Of Chemical Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/63—Esters of sulfonic acids
    • C07C309/64—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms
    • C07C309/65—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms of a saturated carbon skeleton
    • C07C309/66—Methanesulfonates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/26—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids
    • C07C303/30—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reactions not involving the formation of esterified sulfo groups
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/22—Organic complexes
    • B01J31/2282—Unsaturated compounds used as ligands
    • B01J31/2295—Cyclic compounds, e.g. cyclopentadienyls
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
    • C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/01—Sulfonic acids
    • C07C309/62—Sulfonated fats, oils or waxes of undetermined constitution
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
    • C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
    • C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D319/20—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring with substituents attached to the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
    • C07F7/1804—Compounds having Si-O-C linkages
    • C07F7/1872—Preparation; Treatments not provided for in C07F7/20
    • C07F7/1892—Preparation; Treatments not provided for in C07F7/20 by reactions not provided for in C07F7/1876 - C07F7/1888
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/82—Metals of the platinum group
    • B01J2531/822—Rhodium
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

Definitions

  • the present invention relates to an efficient method for preparing highly optically active 2-sulfonyloxy-l-phenylethanol derivatives.
  • Optically active 2-amino-l-phenylethanol derivatives of formula (I) have been used in the preparations of several agricultural chemicals, medical supplies, fine chemicals and building blocks, and 60 biologically active substances having 2-amino- 1 -phenylethanol moiety have been identified to date.
  • drugs containing 2-amino-l-phenylethanol derivatives include blockbuster drugs such as Paroxetine (Paxil, anti-depression agent) and Salmeterol (Seretide, anti-asthma agent) ⁇ Chemistry Today (2006), 24, 40); currently available drugs such as Fluoxetin (Prozac), Sotalol (Bumblece), Formotero (Foradil) and Fexofenadine (Allegra), which are derived from chiral switches in the pipeline ⁇ Nature Rev. Drug Discov.
  • blockbuster drugs such as Paroxetine (Paxil, anti-depression agent) and Salmeterol (Seretide, anti-asthma agent) ⁇ Chemistry Today (2006), 24, 40
  • currently available drugs such as Fluoxetin (Prozac), Sotalol (Bumblece), Formotero (Foradil) and Fexofenadine (Allegra), which are derived from chiral switches in the
  • adrenoceptor agonists such as Tulobuterol, Metaproterenol, Fenoterol and Terbutaline
  • NR1/2B subtype NMDA receptor antagonists such as Ifenprofil and Eliprodil.
  • candidate drugs having 2-amino-l-phenylethanol moiety under development which include adrenoceptor agonists such as Albuterol, Calcimimetics, Terbutaline, Ritodrine, Salmeterol. Suloctidil and Synephrine; NR1/2B subtype NMDA receptor antagonists such as CP-101,606 and Ro-25-6981 ⁇ Bioorg. Med. Chem. Lett.
  • the compound of formula (I) is prepared by a conventional method using essential intermediates of formulae (II) to (TV).
  • X is a halogen atom such as -Cl and -Br, or a leaving group such as mesyloxy (-OMs) and tosyloxy (-OTs);
  • Y is -NH 2 , primary or secondary amine, -N 3 , or -CN; and R is hydrogen, halogen, alkyl, hydroxy, amine, -NO 2 or -CF 3 substituted in the ortho-, metha- or para- position of the phenyl group.
  • the asymmetric reduction of aminoketone using hydrogen at high pressure can be conducted only when the amino group of aminoketone is disubstituted, it is difficult to derivatize the product thereof, and the hydrogen gas used in the reduction is danger.
  • ⁇ -substituent of acetophenones such as -Cl, -N 3 or -CN is known to be harmful to the skin and eyes. Furthermore, it is difficult to apply the method on the mass production due to its poor light stability, and low e.e. (enantiomer excess) value of the product thereof, e.g., ⁇ -azido- or ⁇ -cyano-acetophenone.
  • an object of the present invention to provide an efficient method for preparing optically active 2-sulfonyloxy-l-phenylethanol derivatives.
  • a method for preparing an optically active 2-sulfonyloxy-l-phenylethanol derivative of formula (II) comprising i) reacting (pentamethylcyclopentadienyl)rhodium(III) chloride dimer ([Rh(C 5 Me 5 )Cl 2 ] 2 ) with optically active l,2-diphenylethylene-N-(/7-toluenesulfonyl)diamine (TsDPEN) in methylene chloride and optionally in the presence of triethylamine, and removing the solvent from the reaction product to obtain a rhodium compound; and ii) conducting asymmetrical reduction of an ⁇ -sulfonyloxy acetophenone compound in the presence of the rho
  • X is tosyloxy or mesyloxy
  • substituents each independently, selected from the group consisting of H, F, Cl, Br,
  • the compound of formula (II) can be prepared in a high e.e. value by asymmetrically reducing ⁇ -sulfonyloxy acetophenone compound in the presence of a rhodium compound of formula (V) or (VI) as a catalyst.
  • the rhodium catalyst of formula (V) used in the inventive method is a known material referred to as "TsDPEN-RhCl-Cp*" in the art. Particularly, the rhodium catalyst has been disclosed in several papers, e.g.,
  • the rhodium catalyst of formula (V) may be prepared by methods (A) and (B) described below, and the compound of formula (VI) may be also employed as a catalyst instead of the compound of formula (V):
  • the compound of formula (V) can be easily and efficiently prepared by the methods (A) and (B) in a higher yield than that of the conventional methods, and therefore, the compound of formula (II) obtained in the asymmetrical reduction of ⁇ -chloro acetophenones using the catalyst of formula (V) or (VI) exhibits a higher e.e. (enantiomer excess) value than that of the products obtained in the conventional methods.
  • the ⁇ -sufonyloxy acetophenone compound used in the above process may be prepared by a conventional method; for instance, the ⁇ -tosyloxy acetophenone compound may be prepared by reacting acetophenone with
  • a hydrogen donor which is a compound capable of providing hydrogen by the action of heat or catalysis, is employed, and the exemplary hydrogen donor includes formic acid, a metal or ammonium salt thereof, or an azeotropic mixture of formic acid and an amine such as triethylamine.
  • the asymmetric reduction of the inventive method may be carried out in the presence of an optional solvent, the solvent may be selected from the group consisting of ethylacetate, toluene, methylene chloride, dimethylformamide (DMF), dimethylsulfoxide (DMSO), tetrahydrofuran (THF), acetonitrile and isopropanol.
  • the solvent may be selected from the group consisting of ethylacetate, toluene, methylene chloride, dimethylformamide (DMF), dimethylsulfoxide (DMSO), tetrahydrofuran (THF), acetonitrile and isopropanol.
  • the ⁇ -sulfonyloxy acetophenone compound used as a starting material in the inventive method may be employed in an amount ranging from 100 to 100,000 moles, preferably 1,000 to 10,000 moles based on the metal in the catalyst.
  • the method of the present invention may further comprise conventional purification steps such as extraction, distillation, recrystallization and column chromatography for the purpose of increasing the purity of the product.
  • Example 1 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2.5 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 4 hrs and subjected to a column chromatography to obtain the title compound (yield: 97%).
  • Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.1 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 2 hrs and washed with water, and the combined organic layer was dried over anhydrous sodiumsulfate and filtered. The residue was subjected to a column chromatography to obtain the title compound (yield: 94%).
  • Preparation Example 1 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2.5 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 24 hrs and subjected to a column chromatography to obtain the title compound (yield:
  • Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 30 mins and subjected to a column chromatography to obtain the title compound (yield: 97%).
  • 0.258 g (1 mmol) of l-(2-methoxy-5-methylphenyl)-2-(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of KS]-TsDPEN-RhCl-Cp*/Et 3 N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto.
  • Preparation Example 2 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 35 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 1 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 rnins, the reaction mixture was stirred at room temperature for 18 hrs and subjected to a column chromatography to obtain the title compound (yield:
  • Preparation Example 2 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 40 mins and subjected to a column chromatography to obtain the title compound (yield: 95%).
  • M D 28 +51.5 (c 0.55, CHCl 3 ), 99.2% e.e.,

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Abstract

Optically active 2-sulfonyloxy-1-phenylethanol derivative of formula (II) can be prepared easily and selectively by the method of the present invention using an asymmetric reduction of an α-sulfonyloxy acetophenone compound with a rhodium catalyst having petamethylcyclopentadienyl group and a hydrogen donor, and the compound of formula (II) obtained in the inventive method exhibits a higher e.e. (enantiomer excess) value than that of the products in the conventional methods.

Description

METHOD FOR THE PREPARATION OF OPTICALLY ACTIVE 2-SULFONYLOXY-l-PHENYLETHANOL DERIVATIVES
FIELD OF THE INVENTION
The present invention relates to an efficient method for preparing highly optically active 2-sulfonyloxy-l-phenylethanol derivatives.
BACKGROUND OF THE INVENTION
Optically active 2-amino-l-phenylethanol derivatives of formula (I) have been used in the preparations of several agricultural chemicals, medical supplies, fine chemicals and building blocks, and 60 biologically active substances having 2-amino- 1 -phenylethanol moiety have been identified to date.
Figure imgf000002_0001
(I)
Representative examples of drugs containing 2-amino-l-phenylethanol derivatives include blockbuster drugs such as Paroxetine (Paxil, anti-depression agent) and Salmeterol (Seretide, anti-asthma agent) {Chemistry Today (2006), 24, 40); currently available drugs such as Fluoxetin (Prozac), Sotalol (Betapace), Formotero (Foradil) and Fexofenadine (Allegra), which are derived from chiral switches in the pipeline {Nature Rev. Drug Discov. (2002), 1, 753-768); adrenoceptor agonists such as Tulobuterol, Metaproterenol, Fenoterol and Terbutaline; and NR1/2B subtype NMDA receptor antagonists such as Ifenprofil and Eliprodil. Further, there are several candidate drugs having 2-amino-l-phenylethanol moiety under development, which include adrenoceptor agonists such as Albuterol, Calcimimetics, Terbutaline, Ritodrine, Salmeterol. Suloctidil and Synephrine; NR1/2B subtype NMDA receptor antagonists such as CP-101,606 and Ro-25-6981 {Bioorg. Med. Chem. Lett. (2002), 12, 2615-2619); antidiabetics (US Patent No. 5,817,689); anti-obesity agents (US Patent No. 5,817,689 and J. Med. Chem. (1999), 42, 181-201); and anti-depressants (US Patent No. 4,707,497 and Tetrahedron (2001), 57, 1849-1855).
Generally, the compound of formula (I) is prepared by a conventional method using essential intermediates of formulae (II) to (TV).
Figure imgf000003_0001
Figure imgf000003_0002
Figure imgf000003_0003
wherein, X is a halogen atom such as -Cl and -Br, or a leaving group such as mesyloxy (-OMs) and tosyloxy (-OTs); Y is -NH2, primary or secondary amine, -N3, or -CN; and R is hydrogen, halogen, alkyl, hydroxy, amine, -NO2 or -CF3 substituted in the ortho-, metha- or para- position of the phenyl group. Accordingly, there have been numerous attempts to develop the preparations of optically active intermediates of formulae (II) to (IV). For example, a number of studies disclosed the methods for preparing the compound of formula (II) or (IV), comprising asymmetric reduction of α-substituted acetophenones using oxazaborolidine catalyst and borane (Angew. Chem. Int. Ed. (1998), 37, 1986-2012; Tetrahedron Lett. (1997), 38, 1125-1128; and Tetrahedron Lett. (2001), 42, 8919-8921), asymmetric reduction of α-substituted acetophenones using asymmetric transfer hydrogenation (Org. Lett. (2005), 7, 5489-5491; Org. Lett. (2002), 4, 4373-4376; and Japanese Patent Publication No. 2002-251994); asymmetric reduction of aminoketone using hydrogen at high pressure (J. Am. Chem. Soc. (2000), 122, 6510-6511); synthesis of diol using asymmetric dihydroxylation {Tetraderon: Asymmetry (2004), 15, 3955-3959); asymmetric acylation of α-azidoalcohol using enzymes {Tetraderon: Asymmetry (2004), 15, 3939-3944); or reduction of α-azidoketone using microorganisms (Tetraderon: Asymmetry (2001), 12, 3381-3385; and /. MoI. Cat. B: Enzymatic (2006), 39, 9-12).
Among these methods, the asymmetric reduction of α-substituted acetophenones using oxazaborolidine catalyst and borane is mainly employed in the preparation of the compound of formulae (II) to (IV); however, such method require high cost due to the use of an expensive catalyst in an excess amount, and have the wide fluctuation of the optical activity of the product depending on the substitution of the phenyl moiety, in addition, the reduction is highly sensitive to humidity.
Further, the asymmetric reduction of aminoketone using hydrogen at high pressure can be conducted only when the amino group of aminoketone is disubstituted, it is difficult to derivatize the product thereof, and the hydrogen gas used in the reduction is danger.
Although the asymmetric reduction of α-substituted acetophenones using asymmetric transfer hydrogenation is an effective method for the preparation of the intermediates, α-substituent of acetophenones such as -Cl, -N3 or -CN is known to be harmful to the skin and eyes. Furthermore, it is difficult to apply the method on the mass production due to its poor light stability, and low e.e. (enantiomer excess) value of the product thereof, e.g., α-azido- or α-cyano-acetophenone.
SUMMARY OF THE INVENTION
Accordingly, it is an object of the present invention to provide an efficient method for preparing optically active 2-sulfonyloxy-l-phenylethanol derivatives. In accordance with one aspect of the present invention, mere is provided a method for preparing an optically active 2-sulfonyloxy-l-phenylethanol derivative of formula (II), comprising i) reacting (pentamethylcyclopentadienyl)rhodium(III) chloride dimer ([Rh(C5Me5)Cl2]2) with optically active l,2-diphenylethylene-N-(/7-toluenesulfonyl)diamine (TsDPEN) in methylene chloride and optionally in the presence of triethylamine, and removing the solvent from the reaction product to obtain a rhodium compound; and ii) conducting asymmetrical reduction of an α-sulfonyloxy acetophenone compound in the presence of the rhodium compound having pentamethylcyclopentadienyl group as a catalyst and a hydrogen donor:
Figure imgf000005_0001
wherein,
X is tosyloxy or mesyloxy;
R is one or more substituents, each independently, selected from the group consisting of H, F, Cl, Br, OH5 OMe, OBn, OAc, OTBS, OTs, NH2, NHBn NHBz NHTBS, NHMs, N(Ac)2, N(Ms)2, NO2, CF3, Me, tert-Bu and CH2OMe substituted in the ortho-, metha- or para- position of the phenyl moiety, the substituents being optionally fused together to form a benzene, dioxane or dioxolane ring (Me=methyl, Bn=benzyl, Bu=butyl, Bz=benzoyl, TBS=tert-butyldimethylsilyl, Ms=mesyl, Ac=acetyl, and Ts=tosyl).
DETAILED DESCRIPTION OF THE INVENTION
In the present invention, the compound of formula (II) can be prepared in a high e.e. value by asymmetrically reducing α-sulfonyloxy acetophenone compound in the presence of a rhodium compound of formula (V) or (VI) as a catalyst.
Figure imgf000005_0002
(V)
Figure imgf000006_0001
The rhodium catalyst of formula (V) used in the inventive method is a known material referred to as "TsDPEN-RhCl-Cp*" in the art. Particularly, the rhodium catalyst has been disclosed in several papers, e.g.,
Mashima et al., Chem. Letters (1998), 1199-1200 and Chem. Letters (1998), 1201-1202, which demonstrates that the rhodium catalyst can be obtained in a yield of 70% by reacting 1 equivalent of
(pentamethylcyclopentadienyl)rhodium(III) chloride dimer ([Rh(C5Me5)Cl2J2), 2 equivalent of optically active l,2-diphenylethylene-N-(p-toluenesulfonyl)diamine (TsDPEN) and 4 equivalent of triethylamine in methylene chloride, and washing and recrystallizing the reaction mixture.
In the method of the present invention, the rhodium catalyst of formula (V) may be prepared by methods (A) and (B) described below, and the compound of formula (VI) may be also employed as a catalyst instead of the compound of formula (V):
Method (A) - reacting 1 equivalent of
(pentamethylcyclopentadienyl)rhodium(III) chloride dimer ([Rh(C5Me5)Cl2J2), 2 equivalent of optically active l,2-diphenylethylene-N-(/7-toluenesulfonyl)diamine (TsDPEN) and 4 equivalent of triethylamine in methylene chloride as a solvent to obtain a reaction mixture, and removing the solvent from the reaction mixture to obtain the catalyst of formula (V) in a quantitative yield; and
Method (B) - reacting 1 equivalent of
(petamethylcyclopentadienyl)rhodium(III) chloride dimer ([Rh(C5Me5)Cl2]2) and 2 equivalent of optically active l,2-diphenylemylene-N-(p-toluenesulfonyl)diamine (TsDPEN) in methylene chloride as a solvent, in the absence of triethylamine, to obtain a reaction mixture, and removing the solvent from the reaction mixture to obtain the catalyst of formula (V) in a stoichiometric yield.
The compound of formula (V) can be easily and efficiently prepared by the methods (A) and (B) in a higher yield than that of the conventional methods, and therefore, the compound of formula (II) obtained in the asymmetrical reduction of α-chloro acetophenones using the catalyst of formula (V) or (VI) exhibits a higher e.e. (enantiomer excess) value than that of the products obtained in the conventional methods.
The asymmetrical reduction according to the inventive method is summarized in Reaction Scheme I.
Reaction Scheme I
Figure imgf000007_0001
(X = OXS, OMs) (X = OTS, OMs)
The α-sufonyloxy acetophenone compound used in the above process may be prepared by a conventional method; for instance, the α-tosyloxy acetophenone compound may be prepared by reacting acetophenone with
[hydroxy(tosyloxy)iodido]benzene (which is also referred to as "Koser's reagent") in accordance with a method described in [J. Org. Chem. (1982), 47, 2487-2489], and similarly, the α-mesyloxy acetophenone compound may be prepared by reacting acetophenone with [hydroxyl(mesyloxy)iodido]benzene, as shown in
Reaction Scheme II.
Reaction Scheme II
Figure imgf000007_0002
(X = OTs, OMs)
In the inventive method, it is preferred that a hydrogen donor, which is a compound capable of providing hydrogen by the action of heat or catalysis, is employed, and the exemplary hydrogen donor includes formic acid, a metal or ammonium salt thereof, or an azeotropic mixture of formic acid and an amine such as triethylamine. In case of employing formic acid, a salt thereof, or an azeotropic mixture of formic acid and an amine as a hydrogen donor, the asymmetric reduction of the inventive method may be carried out in the presence of an optional solvent, the solvent may be selected from the group consisting of ethylacetate, toluene, methylene chloride, dimethylformamide (DMF), dimethylsulfoxide (DMSO), tetrahydrofuran (THF), acetonitrile and isopropanol.
The α-sulfonyloxy acetophenone compound used as a starting material in the inventive method may be employed in an amount ranging from 100 to 100,000 moles, preferably 1,000 to 10,000 moles based on the metal in the catalyst. The method of the present invention may further comprise conventional purification steps such as extraction, distillation, recrystallization and column chromatography for the purpose of increasing the purity of the product.
The following Examples are intended to further illustrate the present invention without limiting its scope.
The e.e. values of the l-phenylethane-l,2-diol monosulfonate compounds obtained in the following Examples were determined by HPLC using a column equipped with Chiralcel OD-H, DB-H and OJ-H (Diacel).
Preparation Example 1: Preparation of [S,S]-TsDPEN-RhCl-Cp*/Et3N.HCl
0.10 g (0.16 mmol) of dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer and 0.12 g (0.32 mmol) of (lS,2S)-(-)-N-p-tosyl 1,2-diphenylethylenediamine were placed in a 25 ml two-necked round flask under an argon atmosphere, 5 ml of anhydrous methylene chloride and 90 μl (0.65 mmol) of anhydrous triethyleneamine were added thereto, and the mixture was stirred at room temperature for 2 hrs. The reaction mixture was concentrated under a reduced pressure to remove the solvent and dried for 2 hrs under a high vacuum to obtain 190 mg of the title compound as an orange-colored powder. The obtained compound was kept under an argon atmosphere during the experimental periods of the following Examples.
Preparation Example 2: Preparation of [i?,Λ]-TsDPEN-RliCl-Cp*/Et3N.HCl 12.5 mg (0.02 mmol) of dicMoro(pentamethylcyclopentadienyl)rhodium(III) dimer and 14.6 mg (0.04 mmol) of (ii?,2R)-(-)-N-p-tosyl-l,2-diphenylethylenediamine were placed in a 25 ml two-necked round flask under an argon atmosphere, 2 ml of anhydrous methylene chloride and 11.5 μl (0.08 mmol) of anhydrous triethyleneamine were added thereto, and the mixture was stirred at room temperature for 2 hrs. The reaction mixture was concentrated under a reduced pressure to remove the solvent and dried for 2 hrs under a high vacuum to obtain 35 mg of the title compound as an orange-colored powder. The obtained compound was kept under an argon atmosphere during the experimental periods of the following Examples.
Preparation Example 3: Preparation of [R,R] -TsDPEN-RhCl-Cp*
6.3 mg (0.01 mmol) of dichloroφentamethylcyclopentadieny^rhodium^II) dimer and 7.3 mg (0.02 mmol) of
(7R,2R)-(-)-N-/7-tosyl-l,2-diphenylethylenediamine were placed in a 25 ml two-necked round flask under an argon atmosphere, 1 ml of anhydrous methylene chloride was added thereto, and the mixture was stirred at room temperature for 2 hrs. The reaction mixture was concentrated under a reduced pressure to remove the solvent and dried for 4 hrs under a high vacuum to obtain 12 mg of the title compound as an orange-colored powder. The obtained compound was kept under an argon atmosphere during the experimental periods of the following
Examples.
Preparation Example 4: Preparation of [.9,S]-TsDPEN-RhCl-Cp*
12.3 mg (0.02 mmol) of dichloroφentamethylcyclopentadieny^rhodium^II) dimer and 14.6 mg (0.04 mmol) of (iS,2S)-(-)-N-/7-tosyl-l,2-diphenylethylenediamine were placed in a 25 ml two-necked round flask under an argon atmosphere, 1 ml of anhydrous methylene chloride was added thereto, and the mixture was stirred at room temperature for 2 hrs. The reaction mixture was concentrated under a reduced pressure to remove the solvent and dried for 4 hrs under a high vacuum to obtain 12 mg of the title compound as an orange-colored powder. The obtained compound was kept under an argon atmosphere during the experimental periods of the following Examples. Example 1: Preparation of (i?)-(-)-l-phenyl-2-(p-tolylsulfonyloxy)ethanol
290 mg (1 mmol) of l-phenyl-2-(p-tolylsulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [,S;S]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation
Example 1 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2.5 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 4 hrs and subjected to a column chromatography to obtain the title compound (yield: 97%).
[α]D 25 = -51.3 (c = 2.54, CHCl3), chiral HPLC: 95.0% e.e. (Chiralcel OD-H, 250 x 4.6 mm, hexane:ethanol = 95:5, 0.5 ml/min),
1H NMR (300MHz, CDCl3) δ 7.78 (2H, d, J = 8.4 Hz); 7.36-7.27 (7H, m); 4.99 (IH, ά, J= 8.7 Hz); 4.17 (IH, dd, J= 10.2 and 3.3 Hz); 4.07 (IH, dd, J= 10.2 and 8.7 Hz); 2.55 (OH, d, J= 3 Hz); 2.44 (3H, s).
Example 2: Preparation of
(/2)-(-)-l-(2-methoxyphenyl)-2-(p-tolylsulfonyloxy)ethanol
320 mg (1 mmol) of l-(2-methoxyphenyl)-2-(p- tolylsulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [5;S]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2.5 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 4 hrs and subjected to a column chromatography to obtain the title compound (yield: 99%).
[α]D 25 = .47.9 (c = 2.54, CHCl3), chiral HPLC: 84.6% e.e., 1H NMR (300MHz, CDCl3) δ 7.76 (d, 2H, J = 8.1), 7.38-7.24 (m, 4H), 6.95 (t, IH, J= 7.5), 6.82 (d, IH, J= 8.1), 5.17 (dd, IH, J= 3.3, 8.1), 4.30-4.00 (m, 2H), 3.77 (s, 3H), 2.44 (s, 3H).
Example 3: Preparation of
(i?)-(-)-l-(3-methoxyphenyl)-2-(p-tolylsulfonyloxy)ethanol
320 mg (1 mmol) of l~(3-methoxyphenyl)-2-(p- tolylsulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [SS]-TsDPEN-RhCl-Cp^Et3N-HCl obtained in Preparation Example 1 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas was introduced therein for 10 mins, 2.5 ml of ethylacetate was added thereto to completely dissolve the starting materials, and
0.4 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 2 hrs and subjected to a column chromatography to obtain the title compound (yield:
96%).
[α]D 25 = -37.5 (c = 2.56, CHCl3), chiral HPLC: 93.7% e.e., 1H NMR (300MHz, CDCl3) δ 7.77 (d, 2H, J = 8.4), 7.33 (d, 2H, J = 8.1),
7.27-7.22 (m, IH), 6.88-6.82 (m, 3H), 4.98-4.93 (m, IH), 4.17-4.00 (m, 2H)5 3.79 (s, 3H)52.45 (s, 3H).
Example 4: Preparation of (i?)-(-)-l-(4-methoxyphenyl)-2-(p-tolylsulfonyloxy)ethanol
1.602 g (5 mmol) of l-(4-methoxyphenyl)-2-0?-tolylsulfonyloxy)ethanone and 3.89 mg (0.005 mmol) of [SS]-TsDPEN-RhCl-Cp5VEt3KHCl obtained in Preparation Example 1 were placed in a 100 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 35 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 1 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 18 hrs and subjected to a column chromatography to obtain the title compound (yield:
O/ Or ). [α]D 25 = -49.5 (c = 2.51, CHCl3), 93.6% e.e.,
1H NMR (300MHz, CDCl3) δ 7.77 (d, 2H, J = 8.4), 7.33 (d, 2H, J = 8.1), 7.23 (d, TA, J = 7.2), 6.86 (d, 2H, J = 8.7), 4.92 (dd, IH, J = 3.5, 8.4), 4.13-4.00 (m, 2H), 3.79 (s, 3H), 2.45 (s, 3H).
Example 5: Preparation of
(/?)-l-(4-benzyIoxyphenyl)-2-(^-tolylsulfonyloxy)ethanol
4.36 g (11 mmol) of l-(4-benzyloxyphenyl)-2-(p-tolylsulfonyloxy)ethanone and 9 mg (0.011 mmol) of [S1S]-TsDPEN-RhCl-Cp51VEt3N-Ha obtained in Preparation Example 1 were placed in a 100 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 22 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 2.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 6 hrs and washed with water, and the combined organic layer was dried over anhydrous sodiumsulfate and filtered. The obtained residue was subjected to a column chromatography to obtain the title compound (yield: 82%). mp 91-92 TC,
1H NMR (300 MHz; CDCl3) δ 7.77 (2H, d, J= 8.4 Hz), 7.43-7.32 (6H, m), 7.26-7.20 (3H, m), 6.93 (2H, d, J= 8.8 Hz), 5.05 (2H, s), 4.95 (IH, at, J= 8.3 and 3.0 Hz), 4.13-3.99 (2H, m), 2.44 (3H, s), 13C NMR (DMSO-d6) δ 158.90, 145.04, 136.71, 132.62, 130.51, 129.91,
128.59, 128.02, 127.93, 127.49, 127.40, 114.98, 74.28, 71.49, 69.98, 21.65; EIMS (7OeV) m/z (relative intensity) 398 (M+, 1), 213 (56), 91 (100); [α]D 28 -42.5 (c 0.79, CHCl3), chiral HPLC analysis (Chiralcel OD-H, 250 x 4.6 mm, 2% ethanol/hexane; 1.2 ml/min), 94.8% e.e.
Example 6: Preparation of l-(4-acetoxyphenyl)-2-(p-tolylsulfonyloxy)ethanol
0.174 g (0.5 mmol) of l-(4-acetoxyphenyl)-2-(p-tolylsulfonyloxy)ethanone and 0.4 mg (0.0005 mmol) of [S,5]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in
Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.1 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 2 hrs and washed with water, and the combined organic layer was dried over anhydrous sodiumsulfate and filtered. The residue was subjected to a column chromatography to obtain the title compound (yield: 94%).
1H NMR (300 MHz; CDCl3) δ 7.77 (2H, d, J= 8.4 Hz), 7.36-7.32 (4H, m), 7.06 (2H, d, J= 8.6 Hz), 4.99 (IH, dd, J= 8.5 and 3.2 Hz)5 4.12 (IH, dd, J= 10.4 and 3.4 Hz), 4.01 (IH, dd, J= 10.4 and 8.7 Hz), 2.61 (IH, d, /= 3.2 Hz), 2.45 (3H, s) 2.30 (3H, s),
13C NMR (CDCl3) δ 169.41, 150.63, 145.14, 135.79, 132.44, 129.96, 127.94, 127.32, 121.82, 74.18, 71.37, 21.64, 21.08,
EIMS (7OeV) m/z (relative intensity) 165 (M+-CH2OTs, 39), 123 (100), 91 (17); [α]D 29 -41.20 (c 1.085g, CHCl3), chiral HPLC analysis (Chiralcel OD-H, 250 x 4.6 mm, 5% ethanol/hexane; 0.5 ml/min), 95.5% e.e.
Example 7: Preparation of l-(4-ter^-butyldimethylsilyloxyphenyl)-2-(p-tolylsulfonyloxy)ethanol
0.420 g (0.1 mmol) of l-(4-tert-butyldimethylsilyloxyphenyl)-2-(f»-tolylsulfonyloxy)ethanone and 0.7 mg (0.001 mmol) of [S,S]-TsDPEN-RhCl-Cρ*/Et3N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 2 hrs and washed with water, and the combined organic layer was dried over anhydrous sodiumsulfate and filtered. The obtained residue was subjected to a column chromatography to obtain the title compound (yield: 60%).
1H NMR (300 MHz; CDCl3) δ 7.78 (2H, d, J = 8.3 Hz), 7.34 (2H, d, J = 8.0 Hz), 7.16 (2H, d, J= 8.3 Hz), 6.79 (2H, d, J= 8.6 Hz), 4.92-4.90 (IH, m), 4.11 (IH, dd, /= 10.4 and 3.4 Hz), 4.02 (IH, dd, J= 10.4 and 8.6 Hz), 2.45 (3H, s) 0.97 (9H, s), 0.18 (6H, s), 13C NMR (CDCl3) δ 155.92, 145.03, 132.67, 130.82, 129.92, 127.93, 127.40, 120.23, 74.32, 71.57, 25.62, 21.65, 18.16, -4.46;
EIMS (7OeV) m/z (relative intensity) 422 (M+, 1) 237 (100), 193 (19), 149 (12), 91 (14), [α]D 29 -37.35 (c 1.02g, CHCl3), chiral HPLC analysis (Chiralcel OD-H, 250 x 4.6 mm, 1% ethanol/hexane; 0.4 ml/min), 96.0% e.e.
Example 8: Preparation of (i?)-(-)-l-(2-chlorophenyl)-2-(p-tolylsulfonyloxy)ethanol
324 mg (1 mmol) of l-(2-chlorophenyl)-2-(p-tolylsulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [5,5]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in
Preparation Example 1 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2.5 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 24 hrs and subjected to a column chromatography to obtain the title compound (yield:
42%).
[α]D 25 = -42.1 (c = 0.98, CHCl3),
61.8% e.e.,
1H NMR (300MHz, CDCl3) δ 7.78 (d, 2H5 J= 8.1), 7.58 (d, IH, J = 7.8), 7.34-7.23 (m, 5H), 5.37-5.33 (m, 1H), 4.27 (dd, IH, J = 2.7, 10.8), 4.02-3.95 (m, IH), 2.45 (s, 3H).
Example 9: Preparation of
(i?)-(-)-l-(3-chlorophenyl)-2-(/7-tolylsulfonyloxy)ethanol
324 mg (1 mmol) of l-(3-chlorophenyl)-2-(p-tolylsulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [5f,5]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2.5 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 2 hrs and subjected to a column chromatography to obtain the title compound (yield: 99%). [α]D 25 = -37.8 (c = 2.45, CHCl3),
94.7% e.e.,
1H NMR (300MHz, CDCl3) δ 7.76 (d, 2H5 J = 8.1), 7.35-7.18 (m, 6H)5 4.99-4.94 (m, IH), 4.16-3.99 (m, 2H), 2.46 (s, 3H).
Example 10: Preparation of
(i?)-(-)-l-(4-chlorophenyl)-2-(p-tolylsulfonyloxy)ethanol
324 mg (1 mmol) of l-(4-chlorophenyl)-2-(p-tolylsulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [S,S]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2.5 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 2 hrs and subjected to a column chromatography to obtain the title compound (yield:
94%).
[α]D 25 = -44.8 (c = 2.52, CHCl3), 92.0% e.e., 1H NMR (300MHz5 CDCl3) δ 7.75 (d, 2H5 J = 8.1), 7.35-7.23 (m, 6H)5
4.99-4.94 (m, IH)5 4.15-3.99 (m5 2H), 2.45 (s, 3H).
Example 11: Preparation of
(i?)-(-)-l-(4-nitrophenyl)-2-(p-tolylsulfonyloxy)ethanol
335 mg (1 mmol) of l-(4-nitrophenyl)-2-(/7-tolylsulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [SS]-TsDPEN-RhCl-Cp5VEt3KHCl obtained in Preparation Example 1 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 5 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 2 hrs and subjected to a column chromatography to obtain the title compound (yield: 95%).
MD 25 = -23.6 (c = 1.06, acetone), 68.9% e.e.,
1H NMR (300MHz, CDCl3) δ 8.19 (d, 2H, J = 8.6), 7.75 (d, 2H, J = 8.1), 7.52 (d, 2H, J= 8.5), 7.33 (d, 2H, J= 8.0), 5.12-5.10 (m, IH), 4.22-4.04 (m, 2H), 2.45 (s, 3H).
Example 12: Preparation of
(i?)-(-)-l-(4-methoxy-3-nitrophenyl)-2-(p-tolylsulfonyloxy)ethanol
320 mg (1 mmol) of l-(4-methoxy-3-nitrophenyl)-2-(p-tolylsulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [£S]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 6 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 3 hrs and subjected to a column chromatography to obtain the title compound (yield: 98%).
[α]D 25 = -36.3 (c - 2.49, CHCl3),
84.4% e.e., 1H NMR (300MHz, CDCl3) δ 7.78 (s, IH)5 7.75 (d, 2H, J = 8.4), 7.54 (d,
IH, J = 8.4), 7.34 (d, 2H, J = 8.1), 7.06 (d, IH, J = 8.7), 5.00-4.98 (m, IH), 4.16-4.00 (m, 2H), 2.46 (s, 3H).
Example 13: Preparation of (i?)-(-)-l-(naphthalen-2-yl)-2-(p-tolylsulfonyloxy)ethanol
340 mg (1 mmol) of l-(naphthalen-2-yl)-2-(/7-tolylsulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of KS]-TsDPEN~RhCl-Cp*/Et3N.HCl obtained in
Preparation Example 1 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 5 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 3 hrs and subjected to a column chromatography to obtain the title compound (yield: 98%). [α]D 25 = -49.0 (c = 2.50, CHCl3),
91.8% e.e.,
1H NMR (300MHz, CDCl3) δ 7.83-7.72 (m, 6H), 7.51-7.47 (m, 2H), 7.38 (d, IH, J= 8.7), 7.27-7.25 (m, 2H), 5.15 (dd, IH, J= 3.3, 8.1), 4.27-4.11 (m, 2H), 2.45 (s, 3H).
Example 14: Preparation of
(-R)-(-)-2-hydroxy-5-[l-hydroxy-2-(p-toIylsulfonyIoxy)ethyl]benzoic acid methylester
364 mg (1 mmol) of 2-hydroxy-5-[2-(p-tolylsulfonyloxy)acetyl]benzoic acid methylester and 0.8 mg (0.001 mmol) of [£S]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 10 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 6 hrs and subjected to a column chromatography to obtain the title compound (yield: 52%). [α]D 25 = -3.8 (c = 1.43, CHCl3),
9.8% e.e.,
1H NMR (300MHz, CDCl3) δ 10.75 (s, IH), 7.80-7.74 (m, 3H), 7.40-7.31 (m, 3H), 6.94 (d, IH, /= 8.4), 4.95-4.91 (m, IH), 4.14-4.03 (m, 2H), 3.59 (s, 3H), 2.45 (s, 3H).
Example 15: Preparation of
(J?)-(-)-l-(2,3-dihydro-benzo[l,4]dioxin-6-yl)-2-(p-tolylsulfonyloxy)ethanol
348 mg (1 mmol) of l-(2,3-dihydro-benzo[l,4]dioxin-6-yl)-2-^-tolylsulfonyloxy)ethanone and 0.8 mg
(0.001 mmol) of [S,S]-TsDPEN-RhCl-Cρ*/Et3N.HCl obtained in Preparation Example 1 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 5 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 5 hrs and subjected to a column chromatography to obtain the title compound (yield: 94%).
[α]D 25 = -36.9 (c = 1.73, CHCl3),
1H NMR (300MHz, CDCl3) δ 7.78 (d, 2H, J = 8.4), 7.34 (d, 2H, J = 8.1), 6.83-6.74 (m, 3H), 4.86 (dd, IH, J = 3.6, 8.6), 4.23 (s, 4H), 4.12-3.97 (m, 2H), 2.45 (s, 3H).
Example 16: Preparation of
(12)-(-)-l-(2-bromophenyI)-2-(p-tolylsulfonyloxy)ethanol
369 mg (1 mmol) of l-(2-bromophenyl)-2-(/?-tolylsulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [£S]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 5 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 24 hrs and subjected to a column chromatography to obtain the title compound (yield: 12%). [α]D 25 = -37.7 (c = 0.28, CHCl3),
84.9% e.e.,
1H NMR (300MHz, CDCl3) δ 7.78 (d, 2H5 J = 8.3), 7.57 (d, IH, J = 7.7), 7.47 (d, IH, J = 7.9), 7.34-7.30 (m, 3H), 7.17 (t, IH5 J = 7.7), 5.31-5.29 (m, IH), 4.27 (dd, IH, J= 2.6, 10.5), 4.00-3.94 (m, IH), 2.44 (s, 3H).
Example 17: Preparation of
(i?)-(-)-l-(3-trifluoromethylphenyl)-2-(p-tolylsulfonyloxy)ethanol
358 mg (1 mmol) of l-(3-trifluoromethylphenyl)-2-0?-tolylsulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [S, S] -TsDPEN-RhCl-Cp */Et3N.HCl obtained in Preparation Example 1 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 5 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 2 hrs and subjected to a column chromatography to obtain the title compound (yield: 96%).
[α]D 25 = -31.6 (c = 2.42 CHCl3),
88.1% e.e.,
1H NMR (300MHz, CDCl3) δ 7.74 (d, 2H, J = 8.4), 7.58-7.43 (m, 4H), 7.33 (d, 2H, J= 8.1), 5.07-5.02 (m, IH), 4.19-4.02 (m, 2H), 2.44 (s, 3H).
Example 18: Preparation of
(i?)-(-)-l-(4-methylphenyl)-2-(p-tolylsulfonyloxy)ethanol
304 mg (1 mmol) of l-(4-methylphenyl)-2-(/7-tolylsulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [S,S]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 2 hrs and subjected to a column chromatography to obtain the title compound (yield: 97%). MD 25 = -47.8 (c = 1.27, CHCl3), 98.0% e.e.,
1H NMR (500MHz, CDCl3) δ 7.76 (d, 2H, J = 8.3), 7.32 (d, 2H, J = 8.0), 7.19 (d, 2H, J= 8.0), 7.14 (d, 2H, J = 7.7), 4.94-4.92 (m, IH), 4.13-4.01 (m, 2H), 2.44 (s, 3H), 2.33 (s, 3H).
Example 19: Preparation of
(i?)-(-)-l-(4-fluorophenyl)-2-(p~tolyIsulfonyloxy)ethanol
308 mg (1 mmol) of l-(4-fluorophenyl)-2-(p-tolylsulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [6r,S]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 0.5 hr and subjected to a column chromatography to obtain the title compound (yield: 98%).
[α]D 25 = -34.8 (c = 1.59, CHCl3),
92.7% e.e.,
1H NMR (300MHz, CDCl3) δ 7.76 (d, 2H5 J = 8.2), 7.35-7.28 (m, 4H), 7.01 (t, 2H5 J= 8.6), 4.99-4.94 (m, IH), 4.14-3.99 (m, 2H), 2.45 (s, 3H).
Example 20: Preparation of
(Λ)-(-)-l-(3,4-dimethoxyphenyl)-2-(p-tolylsulfonyloxy)ethanol
320 mg (1 mmol) of l-(3,4-dimethoxyphenyl)-2-(/?-tolylsulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [S,S]-TsDPEN-RhCl-Cρ*/Et3N.HCl obtained in Preparation Example 1 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 8 hrs and subjected to a column chromatography to obtain the title compound (yield: 94%).
[αfo25 = -27.0 (c - 0.83, CHCl3), 89.9% e.e.,
1H NMR (300MHz, CDCl3) δ 7.32 (d, 2H, J = 8.2), 7.75 (d, 2H, J = 8.3), 6.85-6.82 (m, 3H), 4.94-4.90 (m, IH), 4.14-4.02 (m, 2H), 3.86 (s, 3H), 3.84 (s, 3H)5 2.44 (s, 3H).
Example 21: Preparation of
(i?)-(-)-l-(2-methoxy-5-methylphenyl)-2-(p-tolylsuIfonyloxy)ethanol
290 mg (0.86 mmol) of l-(2-methoxy-5-methylphenyl)-2-(p-tolylsulfonyloxy)ethanone and 0.7 mg (0.001 mmol) of KS]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 3 days and subjected to a column chromatography to obtain the title compound (yield: 77%). [α]D 25 = -32.7 (c - 0.65, CHCl3),
89.6% e.e. (this value was determined after converting the product to the acetate form), 1H NMR (300 MHz, CDCl3) δ 7.76 (2H, d, J= 8.3 Hz)5 7.32 (2H, d, J= 8.0
Hz)5 7.15 (IH5 d, J = 1.9 Hz)5 7.05 (IH, dd, J = 8.7 and 1.7 Hz), 6.71 (IH, d, J =
8.3 Hz), 5.15-5.10 (IH, m), 4.25 (IH, dd, J= 10.1 and 3.4 Hz), 4.05 (IH, dd, J = 10.1 and 8.1 Hz), 3.73 (3H5 s), 2.82 (IH, d5 J= 5.3 Hz)5 2.44 (3H, s), 2.26 (3H, s).
Example 22: Preparation of (/2)-2-(methanesulfonyloxy)-l-phenylethanol
0.214 g (1 mmol) of 2-(methanesulfonyloxy)-l-phenylethanone and 0.8 mg (0.001 mmol) of [S,6]-TsDPEN-RhCl-Cρ*/Et3N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 40 mins and subjected to a column chromatography to obtain the title compound (yield: 98%).
[α]D 29 = -50.3 (c 1.10, CHCl3), 97.30% e.e.,
1H NMR (300MHz, CDCl3) δ 7.39-7.30 (5H, m), 5.03-4.98 (IH, m), 4.31 (IH, dd, J= 10.8 and 3.7 Hz), 4.25 (IH, dd, J= 10.8 and 7.8 Hz), 3.15 (IH, ά, J=
3.4 Hz), 2.99 (3H5 s).
Example 23: Preparation of
(l?)-l-(2-chIorophenyl)-2-(methanesulfonyloxy)ethanol
0.248 g (1 mmol) of l-(2-chlorophenyl)-2-(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [S,S]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 30 mins and subjected to a column chromatography to obtain the title compound (yield: 90%). MD 28 = -53.2 (c 1.03 , CHCl3),
76.80% e.e.,
1H NMR (300MHz, CDCl3) δ 7.64 (IH5 d, J = 8.2 Hz), 7.37-7.24 (3H, m), 5.45-5.42 (IH, m), 4.44 (IH, dd, J= 10.9 and 2.6 Hz), 4.22 (IH, dd, J= 10.9 and 8.1 Hz), 3.22 (IH, d, J= 3.0 Hz), 3.06 (3H, s).
Example 24: Preparation of
(i?)-l-(3-chlorophenyl)-2-(methanesulfonyloxy)ethanol
0.248 g (1 mmol) of l-(3-chlorophenyl)-2-(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [S,S]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 30 mins and subjected to a column chromatography to obtain the title compound (yield: 95%). [α]D 28 = -39.0 (c 1.02, CHCl3), 96.44% e.e.,
1H NMR (300MHz, CDCl3) δ 7.41 (IH, s), 7.32-7.24 (3H, m), 5.04-4.99 (IH, m), 4.32 (IH, dd, J = 10.9 and 3.4 Hz), 4.24 (IH, dd, J = 10.8 and 8.0 Hz), 3.24 (IH, d, J= 3.1 Hz), 3.04 (3H, s).
Example 25: Preparation of (ϋ-)-l-(4-chlorophenyl)-2-(methanesuIfonyIoxy)ethanol
0.248 g (1 mmol) of l-(4-chlorophenyl)-2-(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of KS]-TsDPEN-RhCl-Cp51VEt3N1Ha obtained in
Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 30 mins and subjected to a column chromatography to obtain the title compound (yield: 97%).
[α]D 28 = -44.7 (c 1.02, CHCl3), 95.20% e.e.,
1H NMR (300MHz5 CDCl3) δ 7.37-7.31 (4H, m), 5.04-4.99 (IH5 m), 4.30 (IH, dd, J = 10.8 and 3.5 Hz)5 4.23 (IH, dd, J = 10.8 and 8.0 Hz)5 3.08 (IH, d, J= 3.5 Hz), 3.04 (3H, s).
Example 26: Preparation of
(i?)-l-(2-methoxyphenyl)-2-(methanesulfonyloxy)ethanol
0.244 g (1 mmol) of l-(2-methoxyphenyl)-2-(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [S,S]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 24 hrs and subjected to a column chromatography to obtain the title compound (yield: 92%). [α]D 28 - -50.11 (c 1.13, CHCl3), 88.23% e.e.,
1H NMR (300MHz, CDCl3) δ 7.43 (IH, d, J = 7.5 Hz)5 7.31 (IH, t, J= 7.9 Hz)5 7.00 (IH, X, J = 7.5 Hz)5 6.89 (IH, d, J = 8.2 Hz), 5.25 (IH, dd, J = 8.0 and 3.1 Hz), 4.43 (IH, dd, J = 10.7 and 3.1 Hz), 4.31 (IH5 dd, J = 10.7 and 8.0 Hz), 3.85 (3H, s), 3.02 (3H5 s).
Example 27: Preparation of
(i2)-l-(3-methoxyphenyl)-2-(methanesulfonyloxy)ethanol
0.244 g (1 mmol) of l-(3-methoxyphenyl)-2-(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [5,5]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 40 mins and subjected to a column chromatography to obtain the title compound (yield: 97%).
[α]D 28 = -38.9 (c 1.12, CHCl3),
96.73% e.e., 1H NMR (300MHz, CDCl3) δ 7.27 (IH, t, J = 8.2 Hz), 6.95-6.83 (3H5 m),
5.00-4.96 (IH, m), 4.31 (IH, dd, /= 10.8 and 3.6 Hz), 4.25 (IH, dd, J= 10.8 and 8.0 Hz), 3.79 (3H, s), 3.20 (IH, d, J= 3.5 Hz)5 3.01 (3H, s).
Example 28: Preparation of (i?)-l-(4-methoxyphenyl)-2-(methanesulfonyloxy)ethanol
0.244 g (1 mmol) of 4-methoxyphenyl)-2-(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [S,£]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 5 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 4 hrs and subjected to a column chromatography to obtain the title compound (yield: 93%). [α]D 25 = -51.0 (c 1.09, CHCl3),
97.24% e.e.,
1H NMR (300MHz, CDCl3) δ 7.31 (2H, ά, J= 8.7 Hz), 6.91 (2H, d, J= 8.4 Hz), 4.99 (IH, dd, J = 7.5 and 4.5 Hz), 4.30 (IH, dd, J = 11.1 and 4.5 Hz)5 4.26-4.23 (IH, m), 3.81 (3H, s), 3.04 (3H, s).
Example 29: Preparation of
(i?)-2-(methanesulfonyloxy)-l-(naphthaIene-2-yl)ethanol
0.264 g (1 mmol) of 2-(methanesulfonyloxy)-l-(naphthalene-2-yl)ethanone and 0.8 mg (0.001 mmol) of [S,S]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in
Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 40 mins and subjected to a column chromatography to obtain the title compound (yield: 96%). [α]D 28 = -51.4 (c 0.53, CHCl3), 99.27% e.e.,
1H NMR (300MHz, CDCl3) δ 7.88-7.83 (4H, m), 7.52-7.46 (3H3 m), 5.24-5.19 (IH5 m), 4.44 (IH, dd, J= 11.0 and 3.7 Hz), 4.37 (IH, dd, J= 10.9 and 8.0 Hz), 3.04 (3H, s), 2.87 (IH, d, J= 3.4 Hz).
Example 30: Preparation of
(Λ)-l-(4-ferf-butylphenyl)-2-(methanesulfonyloxy)ethanol
0.270 g (1 mmol) of l-(4-tert-butylphenyl)-2-(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [S,5]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and ttiemyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 2 hrs and subjected to a column chromatography to obtain the title compound (yield: 85%). [α]D 25 = -47.9 (c 0.98, CHCl3), 98.98% e.e.,
1H NMR (300MHz, CDCl3) δ 7.41 (2H, d, J= 8.4 Hz)5 7.32 (2H, d, J= 8.3 Hz)5 5.02 (IH, dd, J= 7.5 and 3.7 Hz), 4.34-4.31 (IH5 m)5 4.28 (IH5 dd, /= 10.9 and 7.8 Hz), 3.03 (3H5 s), 1.31 (9H5 s).
Example 31: Preparation of
(i?)-l-(4-acetoxyphenyl)-2-(methanesulfonyloxy)ethanol
0.272 g (1 mmol) of l-(4-acetoxyphenyl)-2-(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [SS]-TsDPEN-RhCl-Cp^Et3KHCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 30 mins and subjected to a column chromatography to obtain the title compound (yield: 97%). [α]D 26 = -41.3 (c 1.05, CHCl3), 97.42% e.e.,
1H NMR (300MHz5 CDCl3) δ 7.41 (2H, d, J= 8.6 Hz), 7.10 (2H5 d, /= 8.47 Hz)5 5.03-5.00 (IH5 m), 4.31 (IH, dd5 J= 10.8 and 3.5 Hz), 4.24 (IH 5dd, J= 10.3 and 8.0 Hz)5 3.02 (3H, s), 2.93 (IH5 d, J= 3.1 Hz)5 2.30 (3H, s).
Example 32: Preparation of
(JR)-l-(4-te/'f-butyl-ώ-inethylsilylphenyl)-2-(methanesuIfonyloxy)ethaiiol
0.344 g (1 mmol) of l-(4-tert-butyl-ώ-methylsilylphenyl)-2-(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [S,S]-TsDPEN-RhCl-Cρ*/Et3N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 rnins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 30 mins and subjected to a column chromatography to obtain the title compound (yield: 68%). [α]D 26 = -35.2 (c 1.02, CHCl3), 97.64% e.e., 1H NMR (300MHz, CDCl3) δ 7.06 (2H, d, J= 8.5 Hz), 6.65 (2H, d, J= 8.0
Hz)5 4.80-4.77 (IH, m), 4.12-4.06 (2H5 m), 2.84 (3H, s), 2.40 (IH, s), 0.75 (9H, s), 0.00 (6H, s).
Example 33: Preparation of (/?)-2-(methanesulfonyloxy)-l-(3-trifluoromethylphenyl)ethanol
0.282 g (1 mmol) of
2-(methanesulfonyloxy)-l-(3-trifluoromethylphenyl)ethanone and 0.8 mg (0.001 mmol) of [£S]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 40 mins and subjected to a column chromatography to obtain the title compound (yield: 91 %). [α]D 28 = -33.3 (c 1.10, CHCl3), 94.12% e.e.,
1H NMR (300MHz, CDCl3) δ 7.69 (IH5 s), 7.59 (2H5 d5 J = 7.4 Hz)5 7.51 (IH5 t, J = 7.5 Hz)5 5.12-5.09 (IH5 m)5 4.35 (IH5 dd, J = 10.9 and 3.4 Hz)5 4.26 (IH5 dd5 J= 10.9 and 8.0 Hz)5 3.43 (IH5 d5 J= 2.8 Hz)5 3.04 (3H, s).
Example 34: Preparation of
(if)-2-(methanesulfonyloxy)-l-(4-trifluoromethylphenyl)ethanol
0.282 g (1 mmol) of 2-(methanesulfonyloxy)-l-(4-trifluoromethylphenyl)ethanone and 0.8 mg (0.001 mmol) of [£S]-TsDPEN-RhCl-Cρ*/Et3N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 rnins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 20 mins and subjected to a column chromatography to obtain the title compound (yield: 98%). [α]D 25 = -37.7 (c 1.16, CHCl3), 95.87% e.e., 1H NMR (300MHz5 CDCl3) δ 7.66 (2H5 d, J = 8.1 Hz)5 7.54 (2H, d, J = 8.1
Hz), 5.14-5.11 (IH, m), 4.36 (IH5 dd5 J= 10.8 and 3.3 Hz)5 4.27 (IH5 dd5 J= 11.1 and 8.1 Hz)5 3.06 (3H5 s), 2.88 (IH5 d, J= 3.6 Hz).
Example 35: Preparation of (l?)-l-(4-fiuorophenyl)-2-(methanesuIfonyIoxy)ethanoI
0.232 g (1 mmol) of l-(4-fluorophenyl)-2-(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [S,S]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 40 mins and subjected to a column chromatography to obtain the title compound (yield: 94%). [α]D 28 = -47.1 (c 1.05, CHCl3),
96.23% e.e., 1H NMR (300MHz, CDCl3) δ 7.41-7.34 (2H5 m), 8.07 (2H5 1, J = 8.7 Hz)5 5.06-5.01 (IH5 m), 4.31 (IH5 dd, /= 10.9 and 3.7 Hz)5 4.24 (IH5 dd, /=10.9 and 8.0 Hz)5 3.04 (3H5 s), 2.96 (IH5 d, J= 3.4 Hz).
Example 36: Preparation of
(β)-l-(3,4-^/-chlorophenyl)-2-(methanesulfonyloxy)ethanol
0.283 g (1 mmol) of l-(3,4-dichlorophenyl)-2-(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [S,S]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 1 hr and subjected to a column chromatography to obtain the title compound (yield: 99%). [α]D 25 = -37.5 (c 0.97, CHCl3), 93.79% e.e.,
1H NMR (300MHz5 CDCl3) δ 7.52 (IH5 d, J= 1.7 Hz)5 7.46 (IH5 d5 J= 8.3 Hz), 7.26 (IH, dd, J= 8.3 and 1.7 Hz)5 5.03-5.00 (IH, m), 4.32 (IH5 dd, J= 10.9 and 3.3 Hz), 4.22 (IH, dd, J= 10.9 and 8.2 Hz)5 3.06 (3H, s), 2.95 (IH, s).
Example 37: Preparation of
(2?)-2-(methanesulfonyloxy)-l-(4-nitrophenyl)ethanol
0.130 g (0.5 mmol) of 2-(methanesulfonyloxy)-l-(4-nitrophenyl)ethanone and 0.4 mg (0.0005 mmol) of [£S]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.1 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 40 mins and subjected to a column chromatography to obtain the title compound (yield: 90%). [α]D 28 = -35.9 (c 0.5I5 Acetone), 87.59% e.e., 1H NMR (300MHz5 DMSO-J6) δ 8.22 (2H5 d, J = 8.6 Hz)5 7.69 (2H5 ά, J = 8.8 Hz)5 5.04-5.00 (IH5 m), 4.30 (IH5 dd5 /= 10.4 and 4.0 Hz)5 4.24 (IH, dd5 J = 10.4 and 6.4 Hz)5 3.12 (3H, s).
Example 38: Preparation of
(2?)-l-(l,4-benzodioxan-6-yl)-2-(methanesulfonyIoxy)ethanol
0.272 g (1 mmol) of l-(l54-benzodioxan-6-yl)-2-(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [S,S]-TsDPEN-RhCl-Cρ*/Et3N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 2 hrs and subjected to a column chromatography to obtain the title compound (yield: 92%).
[α]D 26 = -41.9 (c 1.21, CHCl3),
97.32% e.e.,
1H NMR (300MHz5 CDCl3) δ 6.90-6.85 (3H5 m), 4.92 (IH, dd, J = 7.8 and 3.8 Hz), 4.29-4.22 (6H, m), 3.04 (3H, s).
Example 39: Preparation of
(/?)-l-(2-methoxy-5-methylphenyl)-2-(methanesulfonyloxy)ethanol
0.258 g (1 mmol) of l-(2-methoxy-5-methylphenyl)-2-(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of KS]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 19 hrs and subjected to a column chromatography to obtain the title compound (yield: 91%). [α]D 28 = -42.1 (c 1.21, CHCl3), 89.57% e.e., 1H NMR (300MHz, CDCl3) δ 7.22 (IH, d, J= 1.9 Hz), 7.09 (IH5 dd, J= 8.3 and 2.0 Hz), 6.78 (IH5 d, J= 8.3 Hz), 5.21 (IH, dd, J= 8.1 and 3.1 Hz), 4.40 (IH, J= 10.6 and 3.0 Hz), 4.30 (IH, dd, J= 10.7 and 8.1 Hz), 3.82 (3H, s), 3.03 (3H, s), 2.73 (IH, s), 2.29 (3H, s).
Example 40: Preparation of (i?)-l-(4-methoxy-3-nitrophenyl)-2-(methanesulfonyloxy)ethanol
0.289 g (1 mmol) of l-(4-methoxy-3-nitrophenyl)-2-(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [S,S]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 30 mins and subjected to a column chromatography to obtain the title compound (yield: 90%). [α]D 26 = -41.6 (c 1.04, CHCl3), 92.00% e.e.,
1H NMR (300MHz, CDCl3) δ 7.91 (IH, d, J= 2.1 Hz), 7.59 (IH, dd, J= 8.7 and 2.2 Hz), 7.12 (IH, d, J = 8.7 Hz), 5.07-5.05 (IH, m), 4.33 (IH, dd, J = 10.9 and 3.3 Hz), 4.25 (IH, dd, J= 10.9 and 8.0 Hz), 3.97 (3H, s), 3.08 (3H, s).
Example 41:
(/?)-l-(4-methoxy-3-methoxymethylphenyI)-2-(methanesulfonyloxy)ethanol
0.288 g (1 mmol) of
1 -(4-methoxy~3 -methoxymethylphenyl)-2-(methanesulfonyloxy)etlianone and 0.8 mg (0.001 mmol) of [£S]-TsDPEN-RhCl-Cρ*/Et3N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 4 hrs and subjected to a column chromatography to obtain the title compound (yield: 93%). [α]D 25 = -41.5 (c 1.86, CHCl3), 95.40% e.e., 1H NMR (300MHz, CDCl3) δ 7.38 (IH, d, J = 1.8 Hz), 7.30 (IH, d, J= 8.4 and 2.1 Hz), 6.87 (IH5 d, /= 8.4 Hz), 4.99 (IH, dd, /= 6.6 and 4.8 Hz), 4.48 (2H, s), 4.31-4.27 (2H, m), 3.84 (2H, s), 3.43 (3H, s), 3.04 (3H, s).
Example 42: Preparation of
(i?)-l-(4-N,N'-bis(methanesulfonyl)aminophenyI)-2-(methanesuIfonyloxy)etha nol
0.385 g (1 mmol) of 1 -(4-N,N'-bis(me1nanesulfonyl)aniinoplienyl)-2-(methanesulfonyloxy)etlianone and 0.8 mg (0.001 mmol) of KS]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 1 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 5 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 48 hrs and subjected to a column chromatography to obtain the title compound (yield: 50%). MD 26 = -28.8 (c 0.52, Acetone), 96.5% e.e., 1H NMR (300MHz, Acetone) δ 7.61 (2H, d, J = 8.4 HZ), 7.51 (2H, d, J =
8.4 Hz), 5.16-5.09 (IH, m), 4.36 (IH, dd, /= 10.5 and 3.6 Hz), 4.29 (IH, dd, J = 10.5 and 7.0 Hz), 3.49 (6H, s), 3.05 (3H, s), 2.86 (IH, s).
Example 43: Preparation of (S)-2-chIoro-l-phenylethanoI
155 mg (1 mmol) of 2-chloro-l-phenylethanone and 1.5 mg (0.002 mmol) of [R,R]-TsDPEN-RhCl-Cρ*/Et3N.HCl obtained in Preparation Example 2 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 1 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. After 2 hrs, the reaction mixture was directly loaded on a silica gel (200 mesh) column using 15% EtOAc/hexane as an eluent to obtain 150 mg of the title compound as an liquid (yield: 96%). [α]D 25 = +42.8 (c = 3.88, C6H12), HPLC analysis (Chiralcel OD-H, 250 x 4.6 mm, hexane : ethanol = 95 : 5, 0.5 ml/min): e.e. = 96.3%,
1H NMR (300MHz, CDCl3) δ 7.39-7.29 (5H, m); 4.92 (IH, d, J = 5.7 Hz); 3.72 (IH, dd, J= 11.4 and 3.6 Hz); 3.68 (IH, dd, J= 8.7 and 2.4 Hz); 2.64 (OH, d, J= 2.7 Hz).
Example 44: Preparation of 0S)-2-bromo-l-phenylethanol
199 mg (1 mmol) of 2-bromo-l-phenylethanone and 1.5 mg (0.002 mmol) of [R,R]-TsDPEN-RhCl~Cp*/Et3N.HCl obtained in Preparation Example 2 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 rnins, 1 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. After 24 hrs, the reaction mixture was directly loaded on a silica gel (200 mesh) column using 0~10%
(gradient) EtOAc/hexane as an eluent to obtain 106 mg of the title compound as an liquid (yield: 53%).
[α]D 25 = +13.9 (c = 1.34, CHCl3),
HPLC analysis (Chiralcel OD-H, 250 x 4.6 mm, hexane : ethanol = 95 : 5, 0.5 ml/min): e.e. = 28.3%,
1H NMR (300MHz, CDCl3) δ 7.39-7.29 (5H5 m); 4.95 (IH, m); 3.66 (IH, dd, J = 10.4 and 3.3 Hz); 3.57 (IH, dd, J = 10.4 and 8.8 Hz); 2.63 (OH, d, J = 3Hz).
Example 45: Preparation of (iS)-(+)-l-phenyl-2-(p-tolylsulfonyloxy)ethanol
290 mg (1 mmol) of l-phenyl-2-(p-tolylsulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [R,R]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 2 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 rnins, 2.5 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 rnins, the reaction mixture was stirred at room temperature for 4 hrs and subjected to a column chromatography to obtain the title compound (yield: 97%). [α]D 25 = +51.2 (c = 2.02, CHCl3), chiral HPLC: 95.2% e.e.,
1H NMR (300MHz5 CDCl3) δ 7.78 (2H5 d, J= 8.4 Hz); 7.36-7.27 (7H5 m); 4.99 (IH5 d5 J = 8.7 Hz); 4.17 (IH5 dd, J= 10.2 and 3.3 Hz); 4.07 (IH5 dd, J= 10.2 and 8.7 Hz); 2.55 (OH5 d, J= 3 Hz); 2.44 (3H5 s).
Example 46: Preparation of
(iS)-(+)-l-(4-methoxyphenyl)-2-(/;-tolylsulfonyloxy)ethanol
1.602 g (5 mmol) of l-(4-methoxyphenyl)-2-(p-tolylsulfonyloxy)ethanone and 3.89 mg (0.005 mmol) of [R,R]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in
Preparation Example 2 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 35 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 1 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 rnins, the reaction mixture was stirred at room temperature for 18 hrs and subjected to a column chromatography to obtain the title compound (yield:
94%).
MD 25 = +49.3 (c = 2.46, CHCl3), 94.4% e.e.,
1H NMR (300MHz, CDCl3) δ 7.77 (d, 2H, J = 8.4), 7.33 (d, 2H, J = 8.1), 7.23 (d, 2H, J= 7.2), 6.86 (d, 2H, J = S.I), 4.92 (dd, IH, / = 3.5, 8.4), 4.13-4.00 (m, 2H), 3.79 (s, 3H), 2.45 (s, 3H).
Example 47: Preparation of
(5)-(+)-l-(4-chlorophenyl)-2-(p-tolylsιilfonyloxy)ethanol
324 mg (1 mmol) of l-(4-chlorophenyl)-2-(/7-tolylsulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [R,R]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 2 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2.5 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 2 hrs and subjected to a column chromatography to obtain the title compound (yield: 97%).
MD 25 = +44.9 (c = 2.24, CHCl3), 92.5% e.e., 1H NMR (300MHz, CDCl3) δ 7.75 (d, 2H5 J= 8.1), 7.35-7.23 (m, 6H), 4.99-4.94
(m, IH)5 4.15-3.99 (m, 2H)5 2.45 (s, 3H).
Example 48: Preparation of
(1S)-(+)-l-(naphthalen-2-yl)-2-(p-tolylsulfonyloxy)ethanol
340 mg (1 mmol) of l-(naphthalen-2-yl)-2-(p-tolylsulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [R,R]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 2 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 5 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 3 hrs and subjected to a column chromatography to obtain the title compound (yield: 98%). [α]D 25 = +49.2 (c = 2.58, CHCl3),
92.5% e.e.,
1H NMR (300MHz, CDCl3) δ 7.83-7.72 (m, 6H), 7.51-7.47 (m, 2H), 7.38 (d, IH5 J- 8.7), 7.27-7.25 (m, 2H)5 5.15 (dd, IH, J= 3.3, 8.1), 4.27-4.11 (m, 2H), 2.45 (s, 3H).
Example 49: Preparation of
(5)-(+)-l-(2-methoxy-5-methylphenyl)-2-(p-tolylsulfonyloxy)ethanol
334 mg (1 mmol) of l-(2-methoxy-5-methylphenyl)-2-(p-tolylsulfonyloxy)ethanone and 1.5 mg (0.002 mmol) of [R,R]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 2 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 4 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 9 hrs and subjected to a column chromatography to obtain the title compound (yield: 76%).
[α]D 25 = +32.8 (c = 0.65, CHCl3),
89.7% e.e. (this value was determined after converting the product to the acetate form),
1H NMR (300 MHz, CDCl3) δ 7.76 (2H, d, J= 8.3 Hz), 7.32 (2H, d, J= 8.0 Hz), 7.15 (IH, d, J = 1.9 Hz), 7.05 (IH, dd, J = 8.7 and 1.7 Hz), 6.71 (IH, d, J = 8.3 Hz), 5.15-5.10 (IH, m), 4.25 (IH, dd, J= 10.1 and 3.4 Hz), 4.05 (IH, dd, J = 10.1 and 8.1 Hz), 3.73 (3H, s),2.82 (IH, d, J= 5.3 Hz), 2.44 (3H, s), 2.26 (3H, s).
Example 50: Preparation of (<S)-2-(methanesuIft>nyloxy)-l-phenylethanol
0.215 g (1 mmol) of 2-(methanesulfonyloxy)-l-phenylethanone and 0.8 mg (0.001 mmol) of [R,R]-TsDPEN-RhCl-Cρ*/Et3N.HCl obtained in Preparation Example 2 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 40 mins and subjected to a column chromatography to obtain the title compound (yield: 95%). [α]D 29 = +49.9 (c 1.05, CHCl3), 97.3% e.e.,
1H NMR (300MHz, CDCl3) δ 7.39-7.30 (5H, m), 5.03-4.98 (IH, m), 4.31 (IH, dd, J= 10.8 and 3.7 Hz), 4.25 (IH, dd, J= 10.8 and 7.8 Hz), 3.15 (IH, d, J= 3.4 Hz), 2.99 (3H, s).
Example 51: Preparation of
(iS)-l-(3-chlorophenyl)-2-(methanesulfonyIoxy)ethanol
0.246 g (1 mmol) of l-(3-chlorophenyl)-2-(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [R,R]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 2 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 45 mins and subjected to a column chromatography to obtain the title compound (yield: 97%).
[α]D 28 = +40..0 (c 1.2, CHCl3),
96.4% e.e., 1H NMR (300MHz, CDCl3) δ 7.41 (IH, s), 7.32-7.24 (3H, m), 5.04-4.99
(IH, m), 4.32 (IH, dd, J = 10.9 and 3.4 Hz)5 4.24 (IH, dd, J = 10.8 and 8.0 Hz), 3.24 (IH, d, J= 3.1 Hz)5 3.04 (3H, s).
Example 52: Preparation of (_S)-l-(4-methoxyphenyl)-2-(methanesulfonyloxy)ethanol
0.24 g (1 mmol) of l-(4-methoxyphenyl)-2-(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [R,R]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 2 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 5 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.4 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 4 hrs and subjected to a column chromatography to obtain the title compound (yield: 91%). [α]D 25 = +51.4 (c 1.10, CHCl3),
97.2% e.e.,
1H NMR (300MHz, CDCl3) δ 7.31 (2H5 d, J= 8.7 Hz)5 6.91 (2H5 d, J= 8.4 Hz)5 4.99 (IH, dd, J = 7.5 and 4.5 Hz), 4.30 (IH, dd, J = 11.1 and 4.5 Hz), 4.26-4.23 (IH, m), 3.81 (3H5 s), 3.04 (3H5 s).
Example 53: Preparation of
(iS)-2-(methanesulfonyloxy)-lπ(naphthalene-2-yl)ethanol
0.266 g (1 mmol) of 2-(methanesulfonyloxy)-l-(naphthalene-2-yl)ethanone and 0.8 mg (0.001 mmol) of [R,R]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in
Preparation Example 2 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 40 mins and subjected to a column chromatography to obtain the title compound (yield: 95%). MD 28 = +51.5 (c 0.55, CHCl3), 99.2% e.e.,
1H NMR (300MHz, CDCl3) δ 7.88-7.83 (4H, m), 7.52-7.46 (3H, m), 5.24-5.19 (IH, m), 4.44 (IH, dd, J = 11.0 and 3.7 Hz), 4.37 (IH, dd, J = 10.9 and 8.0 Hz), 3.04 (3H, s), 2.87 (IH, d, J= 3.4 Hz).
Example 54: Preparation of
(5)-l-(4-acetoxyphenyl)-2-(methanesulfonyloxy)ethanol
0.271 g (1 mmol) of l-(4-acetoxyphenyl)-2~(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [R,R]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 2 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 30 mins and subjected to a column chromatography to obtain the title compound (yield: 95%). MD 26 = +41.5 (c 1.02, CHCl3), 97.4% e.e., 1H NMR (300MHz, CDCl3) δ 7.41 (2H, d, J= 8.6 Hz), 7.10 (2H, d, J= 8.47
Hz), 5.03-5.00 (IH, m), 4.31 (IH5 dd, J= 10.8 and 3.5 Hz), 4.24 (IH ,dd, J= 10.3 and 8.0 Hz), 3.02 (3H, s), 2.93 (IH, d, J= 3.1 Hz), 2.30 (3H, s).
Example 55: Preparation of (5)-2-(methanesulfonyloxy)-l-(4-trifluoromethylphenyl)ethanol
0.280 g (1 mmol) of
2-(methanesulfonyloxy)-l-(4-trifluoromethylphenyl)ethanone and 0.8 mg (0.001 mmol) of [R,R]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 2 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 20 mins and subjected to a column chromatography to obtain the title compound (yield: 98%). MD 25 = +37.7 (c 1.15, CHCl3), 95.8% e.e.,
1H NMR (300MHz, CDCl3) δ 7.66 (2H, d, J= 8.1 Hz), 7.54 (2H, d, J= 8.1 Hz), 5.14-5.11 (IH, m), 4.36 (IH5 dd, J= 10.8 and 3.3 Hz), 4.27 (IH, dd, J= 11.1 and 8.1 Hz), 3.06 (3H, s), 2.88 (IH, d, J= 3.6 Hz).
Example 56: Preparation of
(-S)-l-(4-fluorophenyl)-2-(methanesulfonyloxy)ethanol
0.235 g (1 mmol) of l-(4-fluorophenyl)-2-(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [R,R]-TsDPEN-RhCl-Cρ*/Et3N.HCl obtained in Preparation Example 2 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 40 mins and subjected to a column chromatography to obtain the title compound (yield: 95%). [α]D 28 - +47.5 (c 1.15, CHCl3), 96.2% e.e.,
1H NMR (300MHz, CDCl3) δ 7.41-7.34 (2H, m), 8.07 (2H, t, J = 8.7 Hz), 5.06-5.01 (IH, m), 4.31 (IH, dd, J = 10.9 and 3.7 Hz), 4.24 (IH, dd, / =10.9 and 8.0 Hz), 3.04 (3H, s), 2.96 (IH, d, J= 3.4 Hz).
Example 57: Preparation of
(S)-l-(3,4-rf/-chlorophenyl)-2-(methanesulfonyloxy)ethanoI
0.285 g (1 mmol) of l-(3,4-J/-chlorophenyl)-2-(methanesulfonyloxy)ethanone and 0.8 mg (0.001 mmol) of [R,R]-TsDPEN-RhCl-Cp*/Et3N.HCl obtained in Preparation Example 2 were placed in a 25 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. The resulting mixture was stirred at room temperature for 1 hr and subjected to a column chromatography to obtain the title compound (yield: 97%). [α]D 25 = +37.3 (c 1.02, CHCl3),
93.7% e.e., 1H NMR (300MHz5 CDCl3) δ 7.52 (IH5 d, J = 1.7 Hz)5 7.46 (IH5 d, J = 8.3 Hz)5 7.26 (IH, dd, J = 8.3 and 1.7 Hz)3 5.03-5.00 (IH5 m)5 4.32 (IH5 dd, J = 10.9 and 3.3 Hz)5 4.22 (IH, dd, J= 10.9 and 8.2 Hz)5 3.06 (3H5 s), 2.95 (IH5 s).
Example 58: Preparation of (5)-(+)-2-chloro-l-phenylethanol
155 mg (1 mmol) of 2-chloro-l-phenylethanone and 2 mg (0.002 mmol) of [R,R] -TsDPEN-RhCl-Cp* obtained in Preparation Example 3 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 mins, 1 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethyamine (5:2, molar ratio) was added thereto. After 2 hrs, the reaction mixture was directly loaded on a silica gel (200 mesh) column using 15% EtOAc/hexane as an eluent to obtain 148 mg of the title compound as an liquid (yield: 95%). [α]D 25 = +41.6 (c = 5.02, C6H12),
95.3 % e.e.,
1H NMR (300MHz, CDCl3) δ 7.39-7.29 (5H, m); 4.92 (IH, d, J= 5.7 Hz); 3.72 (IH5 dd, J= 11.4 and 3.6 Hz); 3.68 (IH5 dd, J= 8.7and 2.4 Hz); 2.64 (OH, d, J= 2.7 Hz).
Example 59: Preparation of (i?)-(-)-2-chloro-l-phenylethanol
154 mg (1 mmol) of 2-chloro-l-phenylethanone and 0.6 mg (0.001 mmol) of the compound obtained in Preparation Example 4 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 rnins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triemylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 mins, the reaction mixture was stirred at room temperature for 1.5 hrs and subjected to a column chromatography to obtain the title compound
(yield: 93%).
MD 25 = -45.2 (c = 2.63, CHCl3), 97.0% e.e.,
1H NMR (300MHz5 CDCl3) δ 7.39-7.30 (m, 5H), 4.93-4.88 (m, IH)5 3.78-3.62 (m, 2H). Example 60: Preparation of (i?)-(-)-l-phenyl-2-(p-tolylsulfonyloxy)ethanol
290 mg (1 πunol) of l-phenyl-2-(p-tolylsulfonyloxy)ethanone and 0.6 mg
(0.001 mmol) of the compound obtained in Preparation Example 4 were placed in a 10 ml round flask, and the flask was sealed. After introducing argon gas therein for 10 rnins, 2 ml of ethylacetate was added thereto to completely dissolve the starting materials, and 0.2 ml of a mixture of formic acid and triethylamine (5:2, molar ratio) were added thereto. When the color of the reaction mixture changed from light yellow to dark red after 2 to 3 rnins, the reaction mixture was stirred at room temperature for 2 hrs and subjected to a column chromatography to obtain the title compound (yield: 96%).
[α]D 25 = -51.6 (c = 1.24, CHCl3), 95.9% e.e.,
1H NMR (300MHz, CDCl3) δ 7.77 (d, 2H, / = 8.1), 7.42-7.28 (m, 7H), 5.00-4.96 (m, IH), 4.18-4.01 (m, 2H), 2.45 (s, 3H).
While the invention has been described with respect to the above specific embodiments, it should be recognized that various modifications and changes may be made to the invention by those skilled in the art which also fall within the scope of the invention as defined by the appended claims.

Claims

WHAT IS CLAIMED IS:
1. A method for preparing an optically active 2-sulfonyloxy-l-phenylethanol derivative of formula (II), comprising i) reacting (pentamethylcyclopentadienyl)rhodium(III) chloride dimer
([Rh(C5Me5)Cl2J2) with optically active l,2-ώphenylemylene-N-(/7-toluenesulfonyl)diamine (TsDPEN) in methylene chloride and optionally in the presence of triethylamine, and removing the solvent from the reaction product to obtain a rhodium compound; and ii) conducting asymmetrical reduction of an α-sulfonyloxy acetophenone compound in the presence of the rhodium compound having pentamethylcyclopentadienyl group as a catalyst and a hydrogen donor:
Figure imgf000041_0001
wherein,
X is tosyloxy or mesyloxy;
R is one or more substituents, each independently, selected from the group consisting of H, F, Cl, Br, OH, OMe, OBn, OAc, OTBS, OTs, NH2, NHBn
NHBZ NHTBS1 NHMS, N(AC)2, N(MS)2, NO2, CF3, Me, tert-Bu and CH2OMe, substituted in the ortho-, metha- or para- position of the phenyl moiety, the substituents being optionally fused together to form a benzene, dioxane or dioxolane ring (Me=methyl, Bn=benzyl, Bu=butyl, Bz=benzoyl,
TBS=ter£-butyldimethylsiryl, Ms=mesyl, Ac=acetyl, and Ts=tosyl).
2. The method of claim 1, wherein the rhodium compound is represented by formula (V) or (VI):
Figure imgf000042_0001
3. The method of claim 1, wherein the hydrogen donor is formic acid, a metal or ammonium salt thereof, or an azeotropic mixture of formic acid and an amine.
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