Amino alcohol-boron-binol complex and method for preparing optically active amino alcohol derivative by using same

Abstract

Disclosed are an amino alcohol-boron-binol complex as an intermediate, including Complex 3-1-1 shown below, and a method for preparing an optically active amino alcohol by using the same, wherein a racemic amino alcohol is resolved in an enationselective manner using a boron compound and a (R)- or (S)-binol, whereby an amino alcohol derivative with high optical purity can be prepared at high yield. ##STR00001##

Claims

1. A method for preparing an optically active amino alcohol derivative from a racemic amino alcohol, the method comprising: a first step for adding a racemic compound represented by any of the following Chemical Formula 1 with a boron compound, a (R)- or (S)-binol, and a solvent to form an amino alcohol-boron-binol complex represented by any one of the following Chemical Formula 3 as a precipitate; and a second step for hydrolyzing the precipitate of the first step to obtain an optically active amino alcohol derivative: ##STR00050## ##STR00051## ##STR00052## wherein, in the Chemical Formulae 1 and 3, X is CH, C—CH.sub.3 or N; R.sup.1 is a hydrogen or a C.sub.1-C.sub.10 alkyl substituent; R.sup.2 is a substituent selected from the group consisting of a substituted or unsubstituted C.sub.1-C.sub.10 alkyl, a substituted or unsubstituted C.sub.2-C.sub.10 alkenyl, a substituted or unsubstituted C.sub.2-C.sub.10 alkynyl, a substituted or unsubstituted phenyl, a substituted or unsubstituted naphthyl, a substituted or unsubstituted pyrrolyl, a substituted or unsubstituted furanyl, a substituted or unsubstituted pyridinyl, a substituted or unsubstituted pyrimidinyl, and a substituted or unsubstituted pyranyl, wherein the substituted alkyl, alkenyl, alkynyl, phenyl, naphthyl, pyrrolyl, furanyl, pyridinyl, pyrimidinyl, or pyranyl has at least one substituent selected from the group consisting of hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, benzyloxy, and C.sub.1-C.sub.10 alkoxy; R.sup.3 is a substituent selected from the group consisting of a substituted or unsubstituted phenyl, a substituted or unsubstituted thiophenyl, a substituted or unsubstituted pyrrolyl, a substituted or unsubstituted furanyl, a substituted or unsubstituted pyridinyl, a substituted or unsubstituted pyrimidinyl, and a substituted or unsubstituted pyranyl, wherein the substituted phenyl, thiophenyl, pyrrolyl, furanyl, pyridinyl, pyrimidinyl, or pyranyl has at least one substituent selected from the group consisting of hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, and C.sub.1-C.sub.10 alkoxy; R.sup.4 and R.sup.5 are each independently a substituent selected from the group consisting of a substituted or unsubstituted C.sub.1-C.sub.10 alkyl, a substituted or unsubstituted pyrrolyl, a substituted or unsubstituted furanyl, a substituted or unsubstituted pyridinyl, a substituted or unsubstituted pyrimidinyl, and a substituted or unsubstituted pyranyl, wherein the substituted alkyl, pyrrolyl, furanyl, pyridinyl, pyrimidinyl, or pyranyl has at least one substituent selected from the group consisting of hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, and C.sub.1-C.sub.10 alkoxy; or R.sup.4 and R.sup.5 form together a substituted or unsubstituted C.sub.4-C.sub.12 heterocycloalkyl, wherein the substituted heterocycloalkyl has at least one substituent selected from the group consisting of hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, and C.sub.1-C.sub.10 alkoxy; and R.sup.6 is a substituent selected from the group consisting of hydrogen, and a substituted or unsubstituted C.sub.1-C.sub.10 alkyl, wherein the substituted alkyl or aryl has at least one substituent selected from hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, and C.sub.1-C.sub.10 alkoxy.

2. The method of claim 1, wherein the boron compound of the first step is selected from the group consisting of boric acid, trimethyl borate, triethyl borate, triisopropyl borate, tributyl borate, and triphenyl borate.

3. The method of claim 1, wherein the (R)- or (S)-binol of the first step is selected from the chemical structures represented by the following Chemical Formula 2: ##STR00053##

4. The method of claim 1, wherein the solvent in the first step is selected from the group consisting of acetonitrile, dichloromethane, toluene, and isopropanol.

5. The method of claim 1, wherein the boron compound and the (R)- or (S)-binol are added in an amount of 1 mole equivalent and 0.45-0.6 mole equivalents, respectively, based on 1 mole equivalent of the racemic compound represented by Chemical Formula 1 in the first step.

6. An amino alcohol-boron-binol complex represented by any of the following Chemical Formula 3: ##STR00054## ##STR00055## wherein, X is CH, C—CH.sub.3 or N; R.sup.1 is a hydrogen or a C.sub.1-C.sub.10 alkyl substituent; R.sup.2 is a substituent selected from the group consisting of a substituted or unsubstituted C.sub.1-C.sub.10 alkyl, a substituted or unsubstituted C.sub.2-C.sub.10 alkenyl, a substituted or unsubstituted C.sub.2-C.sub.10 alkynyl, a substituted or unsubstituted phenyl, a substituted or unsubstituted naphthyl, a substituted or unsubstituted pyrrolyl, a substituted or unsubstituted furanyl, a substituted or unsubstituted pyridinyl, a substituted or unsubstituted pyrimidinyl, and a substituted or unsubstituted pyranyl, wherein the substituted alkyl, alkenyl, alkynyl, phenyl, naphthyl, pyrrolyl, furanyl, pyridinyl, pyrimidinyl, or pyranyl has at least one substituent selected from the group consisting of hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, benzyloxy, and C.sub.1-C.sub.10 alkoxy; R.sup.3 is a substituent selected from the group consisting of a substituted or unsubstituted phenyl, a substituted or unsubstituted thiophenyl, a substituted or unsubstituted pyrrolyl, a substituted or unsubstituted furanyl, a substituted or unsubstituted pyridinyl, a substituted or unsubstituted pyrimidinyl, and a substituted or unsubstituted pyranyl, wherein the substituted phenyl, thiophenyl, pyrrolyl, furanyl, pyridinyl, pyrimidinyl, or pyranyl has at least one substituent selected from the group consisting of hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, and C.sub.1-C.sub.10 alkoxy; R.sup.4 and R.sup.5 are each independently a substituted with a substituent selected from the group consisting of a substituted or unsubstituted C.sub.1-C.sub.10 alkyl, a substituted or unsubstituted pyrrolyl, a substituted or unsubstituted furanyl, a substituted or unsubstituted pyridinyl, a substituted or unsubstituted pyrimidinyl, and a substituted or unsubstituted pyranyl, wherein the substituted alkyl, pyrrolyl, furanyl, pyridinyl, pyrimidinyl, or pyranyl has at least one substituent selected from the group consisting of hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, and C.sub.1-C.sub.10 alkoxy; or R.sup.4 and R.sup.5 form together a substituted or unsubstituted C.sub.4-C.sub.12 heterocycloalkyl, wherein the substituted heterocycloalkyl has at least one substituent selected from the group consisting of hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, and C.sub.1-C.sub.10 alkoxy; and R.sup.6 is a substituent selected from the group consisting of hydrogen, and a substituted or unsubstituted C.sub.1-C.sub.10 alkyl, wherein the substituted alkyl or aryl has at least one substituent selected from hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, and C.sub.1-C.sub.10 alkoxy.

Description

DESCRIPTION OF THE PREFERRED EMBODIMENTS

(1) The present disclosure provides a method for preparing an optically active amino alcohol derivative from a racemic amino alcohol, the method comprising: (first process) adding a racemic compound represented by the following Chemical Formula 1 with a boron compound, a (R)- or (S)-binol, and a solvent to form an amino alcohol-boron-binol complex as a precipitate; and (second process) hydrolyzing the precipitate of the first process to acquire an optically active amino alcohol derivative:

(2) ##STR00006## wherein, X is CH, C—CH.sub.3 or N; R.sup.1 is substituted with a hydrogen or a C.sub.1-C.sub.10 alkyl substituent; R.sup.2 is substituted with a substituent selected from the group consisting of a substituted or unsubstituted C.sub.1-C.sub.10 alkyl, a substituted or unsubstituted C.sub.2-C.sub.10 alkenyl, a substituted or unsubstituted C.sub.2-C.sub.10 alkynyl, a substituted or unsubstituted C.sub.4-C.sub.12 cycloalkyl, a substituted or unsubstituted C.sub.4-C.sub.12 heterocycloalkyl, a substituted or unsubstituted C.sub.4-C.sub.12 aryl, and a substituted or unsubstituted C.sub.4-C.sub.12 heteroaryl, wherein the substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl has at least one substituent selected from the group consisting of hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, and C.sub.1-C.sub.10 alkoxy; R.sup.3 is substituted with a substituted or unsubstituted C.sub.4-C.sub.12 aryl or a substituted or unsubstituted C.sub.4-C.sub.12 heteroaryl, wherein the substituted aryl or heteroaryl has at least one substituent selected from the group consisting of hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, and C.sub.1-C.sub.10 alkoxy; R.sup.4 and R.sup.5 are each independently substituted with a substituent selected from the group consisting of a substituted or unsubstituted C.sub.1-C.sub.10 alkyl, a substituted or unsubstituted C.sub.4-C.sub.12 heterocycloalkyl, and a substituted or unsubstituted C.sub.4-C.sub.12 heteroaryl, wherein the substituted alkyl, heterocycloalkyl, or heteroaryl has at least one substituent selected from the group consisting of hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, and C.sub.1-C.sub.10 alkoxy; or R.sup.4 and R.sup.5 form together a substituted or unsubstituted C.sub.4-C.sub.12 heterocycloalkyl or a substituted or unsubstituted C.sub.4-C.sub.12 heteroaryl, wherein the substituted heterocycloalkyl or heteroaryl has at least one substituent selected from the group consisting of hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, and C.sub.1-C.sub.10 alkoxy; and R.sup.6 is substituted with a substituent selected from the group consisting of hydrogen, a substituted or unsubstituted C.sub.1-C.sub.10 alkyl, and a substituted or unsubstituted C.sub.4-C.sub.12 aryl, wherein the substituted alkyl or aryl has at least one substituent selected from hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, and C.sub.1-C.sub.10 alkoxy.

(3) The amino alcohol of the present disclosure is an amino alcohol bearing pyridine, pyrimidine, or a tertiary amine, wherein the alcohol moiety may be a primary, secondary, or tertiary alcohol. In addition, the amino alcohol has the chemical structure of 1,2-amino alcohol or 1,3-amino alcohol in which the tertiary amine and the primary, secondary, or tertiary alcohol can form a 5- or 6-membered complex with the boron compound.

(4) In the first process, the boron compound is particularly selected from the group consisting of boric acid, trimethyl borate, triethyl borate, triisopropyl borate, tributyl borate, triphenyl borate, and a combination thereof, but is not limited thereto.

(5) In the first process, (R)- or (S)-binol is selected from the chemical structures represented by the following Chemical Formula 2, but is not limited thereto. A substituted or unsubstituted (R)- or (S)-binol may be used.

(6) ##STR00007##

(7) The solvent in the first process may be selected from the group consisting of acetonitrile, dichloromethane, toluene, isopropanol, and a combination thereof, but any organic solvent may be available without particular limitations thereto.

(8) For a stoichiometric reaction in the first process, the boron compound and the (R)- or (S)-binol are used in amounts of 1 mole equivalent and 0.45-0.6 mole equivalents, respectively, based on 1 mole equivalent of the racemic compound represented by Chemical Formula 1. Given an amount beyond the stoichiometric range, the reaction is conducted insufficiently or produces a byproduct, with the resultant decrease of the optical purify and yield. Hence, the reaction with the stoichiometric amounts is particularly important.

(9) In the second process, the hydrolysis of the precipitate may be achieved with an acid or a base and particularly with oxalic acid, acetic acid, hydrochloric acid, sulfuric acid, nitric acid, sodium hydroxide, lithium hydroxide, or potassium hydroxide, but with no limitations thereto.

(10) After the reaction is terminated in the method of the present disclosure, the optically active amino alcohol derivative may be purified using a typical isolation or purification method such as chromatography, but without limitations thereto.

(11) In addition, the present disclosure relates to an amino alcohol-boron-binol complex (spiroborate ester) represented by the following Chemical Formula 3:

(12) ##STR00008## ##STR00009## wherein, X is CH, C—CH.sub.3 or N; R.sup.1 is substituted with a hydrogen or a C.sub.1-C.sub.10 alkyl substituent; R.sup.2 is substituted with a substituent selected from the group consisting of a substituted or unsubstituted C.sub.1-C.sub.10 alkyl, a substituted or unsubstituted C.sub.2-C.sub.10 alkenyl, a substituted or unsubstituted C.sub.2-C.sub.10 alkynyl, a substituted or unsubstituted C.sub.4-C.sub.12 cycloalkyl, a substituted or unsubstituted C.sub.4-C.sub.12 heterocycloalkyl, a substituted or unsubstituted C.sub.4-C.sub.12 aryl, and a substituted or unsubstituted C.sub.4-C.sub.12 heteroaryl, wherein the substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl has at least one substituent selected from the group consisting of hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, and C.sub.1-C.sub.10 alkoxy; R.sup.3 is substituted with a substituted or unsubstituted C.sub.4-C.sub.12 aryl or a substituted or unsubstituted C.sub.4-C.sub.12 heteroaryl, wherein the substituted aryl or heteroaryl has at least one substituent selected from the group consisting of hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, and C.sub.1-C.sub.10 alkoxy; R.sup.4 and R.sup.5 are each independently substituted with a substituent selected from the group consisting of a substituted or unsubstituted C.sub.1-C.sub.10 alkyl, a substituted or unsubstituted C.sub.4-C.sub.12 heterocycloalkyl, and a substituted or unsubstituted C.sub.4-C.sub.12 heteroaryl, wherein the substituted alkyl, heterocycloalkyl, or heteroaryl has at least one substituent selected from the group consisting of hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, and C.sub.1-C.sub.10 alkoxy; or R.sup.4 and R.sup.5 form together a substituted or unsubstituted C.sub.4-C.sub.12 heterocycloalkyl or a substituted or unsubstituted C.sub.4-C.sub.12 heteroaryl, wherein the substituted heterocycloalkyl or heteroaryl has at least one substituent selected from the group consisting of hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, and C.sub.1-C.sub.10 alkoxy; and R.sup.6 is substituted with a substituent selected from the group consisting of hydrogen, a substituted or unsubstituted C.sub.1-C.sub.10 alkyl, and a substituted or unsubstituted C.sub.4-C.sub.12 aryl, wherein the substituted alkyl or aryl has at least one substituent selected from hydrogen, halogen, hydroxy, amino, cyano, nitro, —S—(C.sub.1-C.sub.10 alkyl), C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.10 alkyl, and C.sub.1-C.sub.10 alkoxy.

(13) The following terms have the following meanings unless otherwise indicated. Any undefined terms have their art recognized meanings.

(14) The term “halogen” refers to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I).

(15) The term “alkyl” refers to a monovalent, linear, or branched hydrocarbon radical. The term includes, by way of example, methyl, ethyl, propyl, n-butyl, isobutyl, tert-butyl, and 1-methylpropyl.

(16) The term “alkenyl” or “alkynyl” refers to a linear or branched hydrocarbon radical bearing one or more double or triple bonds.

(17) The term “alkoxy” refers to an oxygen bonded to a monovalent, linear or branched, saturated hydrocarbon. Alkoxy includes, by way of example, methoxy, ethoxy, propoxy, n-butoxy, tert-butoxy, and 1-methylpropoxy.

(18) The term “cycloalkyl” refers to a monovalent monocyclic saturated hydrocarbon. Cycloalkyl includes, by way of example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

(19) The term “aryl” refers to an aromatic substituent having at least one ring with a p-system of electrons delocalized therein, as exemplified by phenyl, benzyl, etc.

(20) The term “heteroaryl” refers to an aromatic ring compound bearing a heteroatom such as N, O, or S as a ring member. Examples of heteroaryl include pyrrolyl, furanyl, pyridinyl, pyrimidinyl, and pyranyl, according to numbers and kinds of the heteroatoms and numbers of carbon atoms within the ring.

(21) The term “enantiomeric excess (ee)” refers to a parameter of optical purity used for enantiomers in racemic mixtures, reflecting a difference in mole fraction between individual enantiomers in a racemate. A sample with 80 moles of (R)-enantiomer and 20 moles of (S)-enantiomer has an enantiomeric excess (ee) of 180−201=60% for the (R)-enantiomer. Accordingly, an ee of 80% or greater means that the amount of a desired enantiomer accounts for 90% or greater of a racemic mixture.

(22) The present disclosure pertains to an amino alcohol-boron-binol complex as an intermediate and a method for preparation of an optically active amino alcohol by using the same, in which the optical active amino alcohol with a high optical purity can be prepared at high yield from a racemic amino alcohol by chiral resolution using a boron compound and a (R)- or (S)-binol.

(23) A better understanding of the present invention may be obtained through the following examples which are set forth to illustrate, but are not to be construed as limiting the present invention.

Example 1: Preparation and Physicochemical Characterization of Optically Active Amino Alcohol Derivative

1. Preparation of Compound 1: (S)-(4-chlorophenyl)(pyridine-2-yl)methanol

(24) ##STR00010##

(25) (Step 1) To a solution of racemic (4-chlorophenyl) (pyridine-2-yl)methanol (219.7 mg, 1.0 mmol) in acetonitrile (6 ml) was added B(OiPr).sub.3 (188 mg, 1.0 mmol) at room temperature, followed by (R)-binol (128 mg, 0.45 mmol). After stirring at room temperature for 72 hours, the precipitate thus formed was filtered, washed with acetonitrile (1 ml), and then dried to afford an amino alcohol-boron-binol complex (spiroborate complex, 200 mg, yield 38.9%) as a white solid. The HRMS data were as follows:

(26) HRMS (EI) calculated for C.sub.32H.sub.21 BNO.sub.3Cl [M+H].sup.+: 513.1303, found: 513.1303.

(27) The following structure was constructed as analyzed by X-ray diffraction patterns. In detail, the structure accounts for (S)-(4-chlorophenyl)(pyridine-2-yl)methanol-boron-binol complex in which the central atom B is connected to (R)-binol via two B—O bonds and to the substrate via one B—O bond and a B—N coordinate bond.

(28) (Step 2) The spiroborate complex (200 mg, 0.389 mmol) was fractioned between ethyl acetate (30 ml) and 2N HCl (20 ml) and stirred at room temperature for 1 hour. The aqueous layer thus separated was washed with ethyl acetate (10 ml) and the pH was adjusted to 7 with saturated sodium hydrogen carbonate, followed by extraction with dichloromethane (2×20 ml). The extracted organic layers were pooled, dried over anhydrous sodium sulfate, and concentrated to afford Compound 1 (84 mg, 0.38 mmol, 98% ee). Physicochemical data of Compound 1 are given as follows:

(29) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.57-8.51 (m, 1H), 7.69-7.59 (m, 1H), 7.40-7.26 (m, 4H), 7.24-7.13 (m, 2H), 5.74 (d, J=1.5 Hz, 1H), 5.64-5.33 (m, 1H);

(30) .sup.13C NMR (100 MHz, CDCl.sub.3) δ 160.65, 160.63, 148.00, 141.79, 137.03, 133.56, 128.71, 128.41, 122.64, 121.23, 74.43;

(31) HPLC: Chiralpack AD-H column, hexanes:isopropanol=95:5, UV detection at 220 nm, Flow rate 1.0 ml/min, tR (minor isomer)=21.4 min, tR (major isomer)=27.6 min, 98% ee;

(32) [α].sub.D=+90.5 (c 0.5, EtOH).

(33) In the present disclosure, when 0.45 equivalents of a solution of (R)-binol is added to a solution of 1 equivalent of triisopropyl borate in 1 equivalent of racemic-(4-chlorophenyl)(pyridine-2-yl)methanol, precipitation starts to form a white crystal and is completed within 72 hours. The resulting precipitate retains a very high degree of crystallinity and thus is unlikely to dissolve in most NMR solvents, but tends to dissolve in protic or polar solvents. However, molecular ions of the precipitate can be detected using mass spectroscopy. In addition, X-ray crystallography identified the precipitate as a 4-coordinate boron complex having (S)-(4-chlorophenyl)(pyridine-2-yl)methanol. This 4-coordinate boron complex was hydrolyzed in a conventional manner to obtain Compound 1 ((S)-(4-chlorophenyl)(pyridine-2-yl)methanol) with high optical purity.

(34) ##STR00011##

2. Preparation of Compound 2: (R)-(4-chlorophenyl)(pyridine-2-yl)methanol

(35) ##STR00012##

(36) The same procedure as for Compound 1 was conducted, with the exception of using 0.45 equivalents of (S)-binol instead of (R)-binol (128 mg, 0.45 mmol), to prepare Compound 2 (40% yield, 97% ee).

(37) [α].sub.D=−90.1 (c 0.21, EtOH).

3. Preparation of Compound 3: (S)-(4-methoxyphenyl)(pyridine-2-yl)methanol

(38) ##STR00013##

(39) The same procedure as for Compound 1 was conducted, with the exception of using racemic (4-methoxyphenyl)(pyridine-2-yl)methanol (215 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 3 (80 mg, 0.37 mmol, 95% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties thereof, as follows:

(40) HRMS (EI) calculated for C.sub.33H.sub.24BNO.sub.4 [M].sup.+: 507.1798, found: 507.1801;

(41) .sup.1H NMR (500 MHz, CDCl.sub.3) 8.58-8.53 (m, 1H), 7.66-7.59 (m, 1H), 7.33-7.27 (m, 2H), 7.23-7.15 (m, 2H), 6.92-6.85 (m, 2H), 5.74 (s, 1H), 5.30 (s, 1H), 3.80 (s, 3H);

(42) .sup.13C NMR (126 MHz, CDCl.sub.3) 161.32, 159.25, 147.81, 136.84, 135.50, 128.37, 122.35, 121.30, 113.98, 74.63, 55.27;

(43) HPLC: Chiralpack AD-H column, hexanes:isopropanol=95:5, UV detection at 220 nm, Flow rate 0.8 ml/min, tR (minor isomer)=22.31 min, tR (major isomer)=25.80 min, 95% ee;

(44) [α].sub.D=+21.6 (c 0.5, EtOH).

4. Preparation of Compound 4: (S)-(3-methylpyridine-2-yl)(phenyl)methanol

(45) ##STR00014##

(46) The same procedure as for Compound 1 was conducted, with the exception of using racemic (3-methylpyridine-2-yl)(phenyl)methanol (200 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 4 (78 mg, 0.39 mmol, 81% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 4, as follows:

(47) HRMS (EI) calculated for C.sub.33H.sub.24BNO.sub.3 [M].sup.+: 493.1849, found: 493.1854;

(48) .sup.1H NMR (500 MHz, CDCl.sub.3) 8.53-8.39 (m, 1H), 7.49-7.43 (m, 1H), 7.36-7.24 (m, 5H), 7.24-7.18 (m, 1H), 6.29-5.86 (m, 1H), 5.77 (s, 1H), 2.11 (s, 3H);

(49) .sup.13C NMR (126 MHz, CDCl.sub.3) 157.82, 144.88, 142.24, 138.55, 130.37, 128.47, 127.75, 127.67, 122.65, 72.48, 17.82.

(50) HPLC: Chiralpack AD-H column, hexanes:isopropanol=95:5, UV detection at 220 nm, Flow rate 1.0 ml/min, tR (major isomer)=11.23 min, tR (minor isomer), 81% ee;

(51) [α].sub.D=−24.6 (c 0.5, EtOH).

5. Preparation of Compound 5: (S)-benzo[d][1,3]dioxol-5-yl(pyridine-2-yl)methanol

(52) ##STR00015##

(53) The same procedure as for Compound 1 was conducted, with the exception of using racemic benzo[d][1,3]dioxol-5-yl(pyridine-2-yl)methanol (230 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 5 (86 mg, 0.37 mmol, 96% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 5, as follows:

(54) HRMS (EI) calculated for C.sub.33H.sub.22BNO.sub.5 [M].sup.+: 523.1591, found: 523.1590;

(55) .sup.1H NMR (500 MHz, CDCl.sub.3) 8.59-8.54 (m, 1H), 7.67-7.60 (m, 1H), 7.24-7.15 (m, 2H), 6.92-6.87 (m, 1H), 6.84-6.76 (m, 2H), 5.95 5.91 (m, 2H), 5.68 (s, 1H);

(56) .sup.13C NMR (126 MHz, CDCl.sub.3) 160.96, 147.92, 147.80, 147.25, 137.34, 136.88, 122.44, 121.28, 120.76, 108.10, 107.43, 101.04, 74.76.

(57) HPLC: Chiralpack AD-H column, hexanes:isopropanol=90:10, UV detection at 220 nm, Flow rate 0.8 ml/min, tR (minor isomer)=27.32 min, tR (major isomer)=30.80 min, 96% ee;

(58) [α].sub.D=−3.8 (c 0.5, CHCl.sub.3).

6. Preparation of Compound 6: (S)-phenyl(pyridine-2-yl)methanol

(59) ##STR00016##

(60) The same procedure as for Compound 1 was conducted, with the exception of using racemic phenyl(pyridine-2-yl)methanol (186 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 6 (70 mg, 0.38 mmol, 62% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 6, as follows:

(61) HRMS (EI) calculated for C.sub.32H.sub.22BNO.sub.3 [M].sup.+: 479.1693, found: 479.1693;

(62) .sup.1H NMR (400 MHz, CDCl.sub.3) 8.61-8.55 (m, 1H), 7.69-7.60 (m, 1H), 7.47-7.33 (m, 4H), 7.33-7.27 (m, 1H), 7.25-7.15 (m, 2H), 5.79 (d, J=1.9 Hz, 1H), 5.38 (s, 1H);

(63) .sup.13C NMR (100 MHz, CDCl.sub.3) 160.96, 160.94, 147.86, 143.26, 136.87, 128.60, 127.84, 127.09, 122.45, 121.37, 77.41, 77.09, 76.77, 75.03;

(64) HPLC: Chiralpack AD-H column, hexanes:isopropanol=95:5, UV detection at 220 nm, Flow rate 1.0 ml/min, tR (minor isomer)=23.7 min, tR (major isomer)=28.7 min, 62% ee;

(65) [α].sub.D=+20.5 (c 0.5, EtOH).

6-1. Preparation of Compound 6: (S)-phenyl(pyridine-2-yl)methanol

(66) The same procedure as for Compound 6 was conducted, with the exception of using 0.45 equivalents of (R)-3,3′-(CONEt.sub.2).sub.2-binol instead of (R)-binol (128 mg, 0.45 mmol), to prepare Compound 6 at a yield 35% and an ee of 98%.

(67) [α].sub.D=+28.9 (c 0.5, EtOH).

7. Preparation of Compound 7: (S)-(4-fluorophenyl)(pyridine-2-yl)methanol

(68) ##STR00017##

(69) The same procedure as for Compound 1 was conducted, with the exception of using racemic (4-fluorophenyl)(pyridine-2-yl)methanol (204 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 7 (76 mg, 0.37 mmol, 73% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 7, as follows:

(70) HRMS (EI) calculated for C.sub.32H.sub.21BFNO.sub.3 [M].sup.+: 497.1599 found: 497.1599;

(71) .sup.1H NMR (400 MHz, CDCl.sub.3) 8.58-8.52 (m, 1H), 7.71-7.59 (m, 1H), 7.42-7.31 (m, 2H), 7.25-7.13 (m, 2H), 7.07-6.97 (m, 2H), 5.76 (s, 1H), 5.48 (s, 1H);

(72) .sup.13C NMR (100 MHz, CDCl.sub.3) 163.60, 161.16, 160.92, 160.89, 147.94, 139.12, 139.09, 136.97, 128.80, 128.72, 122.55, 121.24, 115.51, 115.29, 74.41;

(73) HPLC: Chiralpack AD-H column, hexanes:isopropanol=95:5, UV detection at 220 nm, Flow rate 1.0 ml/min, tR (minor isomer)=13.0 min, tR (major isomer)=15.36 min, 73% ee;

(74) [α].sub.D=+60.0 (c 0.5, EtOH).

8. Preparation of Compound 8: (S)-pyridin-2-yl(o-tolyl)methanol

(75) ##STR00018##

(76) The same procedure as for Compound 1 was conducted, with the exception of using racemic pyridine-2-yl(o-tolyl)methanol (200 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 8 (82 mg, 0.38 mmol, 57% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 8, as follows:

(77) HRMS (EI) calculated for C.sub.33H.sub.24BNO.sub.3 [M].sup.+: 493.1849, found: 493.1847;

(78) .sup.1H NMR (500 MHz, CDCl.sub.3) 8.67-8.53 (m, 1H), 7.70-7.57 (m, 1H), 7.31-7.25 (m, 1H), 7.25-7.17 (m, 4H), 7.09-7.03 (m, 1H), 6.00 (s, 1H), 2.36 (s, 3H);

(79) .sup.13C NMR (126 MHz, CDCl.sub.3) 160.89, 147.75, 140.59, 136.81, 136.20, 130.78, 127.97, 127.77, 126.10, 122.27, 121.18, 77.26, 77.01, 76.75, 72.75, 19.41;

(80) HPLC: Chiralpack AD-H column, hexanes:isopropanol=95:5, UV detection at 220 nm, Flow rate 1.0 ml/min, tR (minor isomer)=18.2 min, tR (major isomer)=22.48 min, 57% ee.

(81) [α].sub.D=+10.2 (c 0.5, EtOH).

8-1. Preparation of Compound 8: (S)-pyridine-2-yl(o-tolyl)methanol

(82) The same procedure as for Compound 8 was conducted, with the exception of using 0.45 equivalents of (R)-3,3′-(CONEt.sub.2).sub.2-binol instead of (R)-binol (128 mg, 0.45 mmol), to prepare Compound 8 at a yield of 35% and an ee of 86%.

(83) [α].sub.D=+32.3 (c 0.5, EtOH).

9. Preparation of Compound 9: (S)-(4-methylphenyl)(pyridine-2-yl)methanol

(84) ##STR00019##

(85) The same procedure as for Compound 1 was conducted, with the exception of using racemic (4-methylphenyl)(pyridine-2-yl)methanol (200 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 9 (80 mg, 0.40 mmol, 79% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 9, as follows:

(86) HRMS (EI) calculated for C.sub.33H.sub.24BNO.sub.3 [M].sup.+: 493.1849, found: 493.1851;

(87) .sup.1H NMR (500 MHz, CDCl.sub.3) 8.61-8.57 (m, 1H), 7.67-7.60 (m, 1H), 7.29 (d, J=8.1 Hz, 3H), 7.25-7.15 (m, 4H), 5.75 (d, J=4.0 Hz, 1H), 5.24 (d, J=4.3 Hz, 1H), 2.35 (s, 3H);

(88) .sup.13C NMR (126 MHz, CDCl.sub.3) 161.22, 147.83, 140.36, 137.51, 136.84, 129.27, 127.02, 122.36, 121.33, 74.88, 21.17;

(89) HPLC: Chiralpack AD-H column, hexanes:isopropanol=90:10, UV detection at 220 nm, Flow rate 0.8 ml/min, tR (minor isomer)=12.62 min, tR (major isomer)=14.35 min, 79% ee;

(90) [α].sub.D=+24.2 (c 0.5, EtOH).

10. Preparation of Compound 10: (S)-(3-methylphenyl)(pyridine-2-yl)methanol

(91) ##STR00020##

(92) The same procedure as for Compound 1 was conducted, with the exception of using racemic (3-methylphenyl)(pyridine-2-yl)methanol (200 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 10 (72 mg, 0.36 mmol, 89% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 10, as follows:

(93) HRMS (EI) calculated for C.sub.33H.sub.24BNO.sub.3 [M].sup.+: 493.1849, found: 493.1843;

(94) .sup.1H NMR (500 MHz, CDCl.sub.3) 8.55 (s, 1H), 7.65-7.60 (m, 1H), 7.25-7.16 (m, 5H), 7.10 (d, J=7.5 Hz, 1H), 5.73 (s, 1H), 5.26 (br s, 1H), 2.33 (s, 3H);

(95) .sup.13C NMR (126 MHz, CDCl.sub.3) 161.22, 147.83, 143.15, 138.32, 136.84, 128.63, 128.53, 127.71, 124.23, 122.42, 121.43 75.0, 21.54;

(96) HPLC: Chiralpack AD-H column, hexanes:isopropanol=90:10, UV detection at 220 nm, Flow rate 0.8 ml/min, tR (minor isomer)=12.62 min, tR (major isomer)=14.35 min, 89% ee;

(97) [α].sub.D=+64.1 (c 0.5, EtOH).

11. Preparation of Compound 11: (S)-(perfluorophenyl)(pyridine-2-yl)methanol

(98) ##STR00021##

(99) The same procedure as for Compound 1 was conducted, with the exception of using racemic (perfluorophenyl)(pyridine-2-yl)methanol (275 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 11 (105 mg, 0.38 mmol, 91% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 11, as follows:

(100) HRMS (EI) calculated for C.sub.32H.sub.17BF.sub.5NO.sub.3 [M].sup.+: 569.1222, found: 569.1228;

(101) .sup.1H NMR (400 MHz, CDCl.sub.3) 8.64-8.58 (m, 2H), 7.81-7.67 (m, 2H), 7.30 (d, 2H), 7.21 (d, J=7.9 Hz, 2H), 6.19 (s, 2H), 5.50 (s, 1H);

(102) .sup.13C NMR (100 MHz, CDCl.sub.3) 157.40, 147.98, 137.33, 123.18, 120.38, 77.35, 77.04, 76.72, 65.58;

(103) HPLC: Chiralpack AD-H column, hexanes:isopropanol=95:5, UV detection at 220 nm, Flow rate 0.8 ml/min, tR (minor isomer)=16.86 min, tR (major isomer)=19.28 min, 91% ee;

(104) [α].sub.D=−10.8 (c 0.75, CHCl.sub.3).

12. Preparation of Compound 12: (S)-(3,4-dimethoxyphenyl)(pyridine-2-yl)methanol

(105) ##STR00022##

(106) The same procedure as for Compound 1 was conducted, with the exception of using racemic (3,4-dimethoxyphenyl)(pyridine-2-yl)methanol (245 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 12 (92 mg, 0.375 mmol, 96% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 12, as follows:

(107) HRMS (EI) calculated for C.sub.34H.sub.26BNO.sub.5 [M].sup.+: 539.1904, found: 539.1900;

(108) .sup.1H NMR (500 MHz, CDCl.sub.3) 8.59-8.54 (m, 1H), 7.67-7.60 (m, 1H), 7.24-7.14 (m, 2H), 6.96-6.91 (m, 1H), 6.91-6.88 (m, 1H), 6.87 6.81 (m, 1H), 5.71 (s, 1H), 5.31 (s, 1H), 3.87 (s, 3H), 3.84 (s, 3H);

(109) .sup.13C NMR (126 MHz, CDCl.sub.3) 161.12, 149.20, 148.72, 147.79, 136.86, 135.84, 122.40, 121.28, 119.58, 110.93, 109.98, 74.82, 55.90, 55.83;

(110) HPLC: Chiralpack AD-H column, hexanes:isopropanol=90:10, UV detection at 220 nm, Flow rate 0.8 ml/min, tR (major isomer)=27.32 min, tR (minor isomer)=28.2 min, 96% ee;

(111) [α].sub.D=−23.2 (c 0.5, EtOH).

13. Preparation of Compound 13: (S)-(2-methylphenyl)(pyrimidine-2-yl)methanol

(112) ##STR00023##

(113) The same procedure as for Compound 1 was conducted, with the exception of using racemic (2-methylphenyl)(pyrimidine-2-yl)methanol (200 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 13 (72 mg, 0.36 mmol, 71% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 13, as follows:

(114) HRMS (EI) calculated for C.sub.33H.sub.23BN.sub.2O.sub.3 [M].sup.+: 494.1802, found: 494.1810;

(115) .sup.1H NMR (500 MHz, CDCl.sub.3) 8.75 (d, J=4.9 Hz, 2H), 7.25-7.14 (m, 5H), 6.14 (d, J=4.3 Hz, 1H), 4.93 (d, J=4.8 Hz, 1H), 2.53 (s, 3H);

(116) .sup.13C NMR (126 MHz, CDCl.sub.3) 170.23, 156.90, 140.21, 136.46, 130.69, 127.81, 127.22, 126.00, 119.42, 72.89, 19.59;

(117) HPLC: Chiralpack AD-H column, hexanes:isopropanol=95:5, UV detection at 220 nm, Flow rate 0.8 ml/min, tR (minor isomer)=18.18 min, tR (major isomer)=22.48 min, 71% ee;

(118) [α].sub.D=+32.4 (c 0.5, EtOH).

14. Preparation of Compound 14: (S)-(4-(benzyloxy)phenyl)(pyridine-2-yl)methanol

(119) ##STR00024##

(120) The same procedure as for Compound 1 was conducted, with the exception of using racemic (4-(benzyloxy)phenyl)(pyridine-2-yl)methanol (292 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 14 (118 mg, 0.40 mmol, 96% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 14, as follows:

(121) HRMS (EI) calculated for C.sub.39H.sub.28BNO.sub.4 [M].sup.+: 585.2111, found: 585.2103;

(122) .sup.1H NMR (500 MHz, CDCl.sub.3) 8.63-8.58 (m, 1H), 7.84 (d, J=1.7 Hz, 1H), 7.74 (dd, J=16.9, 8.7 Hz, 2H), 7.62 (td, J=7.7, 1.7 Hz, 1H), 7.42 (dd, J=8.5, 1.8 Hz, 1H), 7.24-7.15 (m, 3H), 7.15 7.11 (m, 1H), 5.92 (s, 1H), 3.93 (s, 3H);

(123) .sup.13C NMR (126 MHz, CDCl.sub.3) 160.85, 157.70, 147.70, 138.22, 136.82, 134.17, 129.43, 128.74, 128.61, 127.32, 125.97, 125.32, 122.36, 121.42, 118.88, 105.63, 75.03, 55.23;

(124) HPLC: Chiralpack AD-H column, hexanes:isopropanol=90:10, UV detection at 220 nm, Flow rate 0.8 ml/min, tR (minor isomer)=26.34 min, tR (major isomer)=28.37 min, 96% ee;

(125) [α].sub.D=−3.6 (c 0.5, EtOH).

15. Preparation of Compound 15: (S)-(naphthalen-1-yl)(pyridine-2-yl)methanol

(126) ##STR00025##

(127) The same procedure as for Compound 1 was conducted, with the exception of using racemic naphthalen-1-yl(pyridine-2-yl)methanol (236 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 15 (90 mg, 0.38 mmol, 87% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 15, as follows:

(128) HRMS (EI) calculated for C.sub.36H.sub.24BNO.sub.3 [M].sup.+: 529.1849, found: 529.1857;

(129) .sup.1H NMR (500 MHz, CDCl.sub.3) 8.71-8.66 (m, 1H), 8.17-8.10 (m, 1H), 7.93-7.87 (m, 1H), 7.87-7.82 (m, 1H), 7.61-7.55 (m, 1H), 7.55 7.51 (m, 1H), 7.51-7.43 (m, 4H), 7.27-7.21 (m, 1H), 7.11-7.05 (m, 1H), 6.44 (d, J=1.9 Hz, 1H), 5.43 (d, J=3.0 Hz, 1H);

(130) .sup.13C NMR (100 MHz, CDCl.sub.3) 161.16, 147.94, 138.22, 136.94, 134.24, 131.29, 128.80, 128.78, 126.20, 126.17, 125.63, 125.38, 124.47, 122.47, 121.44, 73.62;

(131) HPLC: Chiralpack AD-H column, hexanes:isopropanol=90:10, UV detection at 220 nm, Flow rate 0.8 ml/min, tR (major isomer)=21.32 min, tR (minor isomer)=26.02 min, 87% ee;

(132) [α].sub.D=+64.3 (c 0.75, CHCl.sub.3).

16. Preparation of Compound 16: (S)-(6-methoxynaphthalen-2-yl)(pyridine-2-yl)methanol

(133) ##STR00026##

(134) The same procedure as for Compound 1 was conducted, with the exception of using racemic (6-methoxynaphthalen-2-yl)(pyridine-2-yl)methanol (265 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 16 (100 mg, 0.376 mmol, 90% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 16, as follows:

(135) HRMS (EI) calculated for C.sub.37H.sub.26BNO.sub.4 [M].sup.+: 559.1955, found: 559.1961;

(136) .sup.1H NMR (500 MHz, CDCl.sub.3) 8.65-8.60 (m, 1H), 7.86-7.79 (m, 1H), 7.79-7.67 (m, 2H), 7.67-7.60 (m, 1H), 7.44-7.38 (m, 1H), 7.26 7.21 (m, 1H), 7.21-7.15 (m, 2H), 7.14 (d, J=2.5 Hz, 1H), 5.91 (d, J=3.4 Hz, 1H), 5.40 (d, J=4.1 Hz, 1H), 3.94 (s, 3H);

(137) .sup.13C NMR (126 MHz, CDCl.sub.3) 160.85, 157.70, 147.70, 138.22, 136.82, 134.17, 129.43, 128.74, 128.61, 127.32, 125.97, 125.32, 122.36, 121.42, 118.88, 105.63, 75.03, 55.23;

(138) HPLC: Chiralpack AD-H column, hexanes:isopropanol=90:10, UV detection at 220 nm, Flow rate 0.8 ml/min, tR (minor isomer)=31.41 min, tR (major isomer)=36.36 min, 90% ee;

(139) [α].sub.D=−121.2 (c 0.1, CHCl.sub.3).

17. Preparation of Compound 17: (S)-(4-(methylthio)phenyl)(pyridine-2-yl)methanol

(140) ##STR00027##

(141) The same procedure as for Compound 1 was conducted, with the exception of using racemic (4-(methylthio)phenyl)(pyridine-2-yl)methanol (232 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 17 (86 mg, 0.37 mmol, 78% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 17, as follows:

(142) HRMS (EI) calculated for C.sub.33H.sub.24BNO.sub.3S [M].sup.+: 525.1570, found: 525.1578;

(143) .sup.1H NMR (500 MHz, CDCl.sub.3) 8.59-8.54 (m, 1H), 7.67-7.60 (m, 1H), 7.34-7.28 (m, 2H), 7.26-7.18 (m, 3H), 7.17 (d, J=7.9 Hz, 1H), 5.74 (s, 1H), 2.47 (s, 3H);

(144) .sup.13C NMR (100 MHz, CDCl.sub.3) 160.81, 147.88, 140.19, 138.03, 136.89, 127.60, 126.77, 122.49, 121.31, 74.60, 15.87;

(145) HPLC: Chiralpack AD-H column, hexanes:isopropanol=90:10, UV detection at 220 nm, Flow rate 0.8 ml/min, tR (minor isomer)=22.7 min, tR (major isomer)=26.08 min, 78% ee;

(146) [α].sub.D=−15.4 (c 1.0, CHCl.sub.3).

18. Preparation of Compound 18: (S)-(3-nitrophenyl)(pyridine-2-yl)methanol

(147) ##STR00028##

(148) The same procedure as for Compound 1 was conducted, with the exception of using racemic (3-nitrophenyl)(pyridine-2-yl)methanol (230 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 18 (81.2 mg, 0.35 mmol, 82% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 18, as follows:

(149) HRMS (EI) calcd for C.sub.32H.sub.21BN.sub.2O.sub.5 [M].sup.+: 524.1544, found: 524.1551;

(150) .sup.1H NMR (400 MHz, CDCl.sub.3) 8.55-8.48 (m, 1H), 8.31-8.24 (m, 1H), 8.14-8.05 (m, 1H), 7.82-7.72 (m, 1H), 7.72-7.62 (m, 1H), 7.48 (t, J=7.9 Hz, 1H), 7.28-7.18 (m, 2H), 5.87 (s, 1H), 5.72 (s, 1H);

(151) .sup.13C NMR (100 MHz, CDCl.sub.3) 159.87, 148.35, 148.28, 145.43, 137.39, 133.05, 129.51, 123.06, 122.70, 121.79, 121.23, 74.23;

(152) HPLC: Chiralpack AD-H column, hexanes:isopropanol=90:10, UV detection at 220 nm, Flow rate 0.8 ml/min, tR (minor isomer)=17.36 min, tR (major isomer)=20.72 min, 82% ee;

(153) [α].sub.D=−21.6 (c 1.25, CHCl.sub.3).

19. Preparation of Compound 19: (S)-(2,5-dimethoxyphenyl)(pyridine-2-yl)methanol

(154) ##STR00029##

(155) The same procedure as for Compound 1 was conducted, with the exception of using racemic (2,5-dimethoxyphenyl)(pyridine-2-yl)methanol (245 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 19 (95 mg, 0.389 mmol, 63% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 19, as follows:

(156) HRMS (EI) calcd for C.sub.34H.sub.26BNO.sub.5 [M].sup.+: 539.1904, found: 539.1551;

(157) .sup.1H NMR (400 MHz, CDCl.sub.3) 8.59-8.48 (m, 1H), 7.64-7.56 (m, 1H), 7.34-7.28 (m, 1H), 7.20-7.12 (m, 1H), 6.98-6.91 (m, 1H), 6.89 6.82 (m, 1H), 6.82-6.74 (m, 1H), 6.20 (s, 1H), 5.37 (s, 1H), 3.83 (s, 3H), 3.73 (s, 3H);

(158) .sup.13C NMR (100 MHz, CDCl.sub.3) 161.05, 153.92, 150.88, 147.71, 136.74, 132.86, 122.27, 121.28, 113.52, 113.32, 112.07, 69.01, 56.18, 55.66;

(159) HPLC: Chiralpack AD-H column, hexanes:isopropanol=95:5, UV detection at 220 nm, Flow rate 0.8 ml/min, tR (minor isomer)=26.6 min, tR (major isomer)=29.3 min, 63% ee;

(160) [α].sub.D=−83.0 (c 0.5, EtOH).

20. Preparation of Compound 20: (1S)-1-phenyl-1-(pyridine-2-yl)ethan-1-ol

(161) ##STR00030##

(162) The same procedure as for Compound 1 was conducted, with the exception of using racemic 1-phenyl-1-(pyridine-2-yl)ethan-1-ol (200 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methano 1 (219.7 mg, 1.0 mmol), to prepare Compound 20 (72 mg, 0.36 mmol, 99% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 20, as follows:

(163) HRMS (EI) calcd for C.sub.32H.sub.21BN.sub.2O.sub.5 [M].sup.+: 493.1849, found: 493.1849;

(164) .sup.1H NMR (400 MHz, CDCl.sub.3) 8.58-8.52 (m, 1H), 7.71-7.61 (m, 1H), 7.59-7.50 (m, 2H), 7.43-7.30 (m, 3H), 7.31-7.24 (m, 1H), 7.28 7.13 (m, 2H), 5.92 (d, J=2.2 Hz, 1H), 1.98 (s, 2H);

(165) .sup.13C NMR (100 MHz, CDCl.sub.3) 164.83, 147.44, 147.22, 137.03, 128.25, 127.01, 125.95, 122.08, 120.34, 77.50, 77.18, 76.86, 75.15, 29.31;

(166) HPLC: Chiralpack AD-H column, hexanes:isopropanol=95:5, UV detection at 220 nm, Flow rate 0.5 ml/min, tR (minor isomer)=19.2 min, tR (major isomer)=20.6 min, 99% ee;

(167) [α].sub.D=+21.6 (c 1.5, CHCl.sub.3).

21. Preparation of Compound 21: (S)-1-(4-chlorophenyl)-1-(pyridine-2-yl)ethan-1-ol

(168) ##STR00031##

(169) The same procedure as for Compound 1 was conducted, with the exception of using racemic 1-(4-chlorophenyl)-1-(pyridine-2-yl)ethan-1-ol (234 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 21 (95 mg, 0.36 mmol, 57% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 21, as follows:

(170) HRMS (EI) calcd for C.sub.33H.sub.23BClNO.sub.3 [M].sup.+: 527.1460, found: 527.1457;

(171) .sup.1H NMR (400 MHz, CDCl.sub.3) 8.57-8.51 (m, 1H), 7.75-7.63 (m, 1H), 7.51-7.41 (m, 2H), 7.36-7.26 (m, 3H), 7.25-7.17 (m, 1H), 5.88 (d, J=1.8 Hz, 1H), 1.93 (s, 3H);

(172) .sup.13C NMR (100 MHz, CDCl.sub.3) 164.27, 147.55, 145.82, 137.15, 132.86, 128.32, 127.46, 122.26, 120.16, 77.43, 77.11, 76.79, 74.81, 29.22;

(173) The ee was determined by HPLC with CHIRAL AD C18 Column (5 m, 4.6 150 mm) (Hexanes:IPA=95:5, UV detection at 220 nm, Flow rate 0.5 ml/min) tR (minor isomer)=19.2 min, tR (major isomer)=20.6 min, 57% ee;

(174) [α].sub.D=+12.4 (c 1.5, CHCl.sub.3).

22. Preparation of Compound 22: (S)-2-methyl-1-(pyridine-2-yl)propan-1-ol

(175) ##STR00032##

(176) The same procedure as for Compound 1 was conducted, with the exception of using racemic 2-methyl-1-(pyridine-2-yl)propan-1-ol (152 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 22 (57 mg, 0.376 mmol, 71% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 22, as follows:

(177) HRMS (EI) calcd for C.sub.29H.sub.24BNO.sub.3 [M].sup.+: 445.1849, found: 445.1854;

(178) .sup.1H NMR (400 MHz, CDCl.sub.3) 8.76-8.28 (m, 1H), 7.87-7.47 (m, 1H), 7.47-7.03 (m, 2H), 4.84-4.24 (m, 2H), 2.14-1.81 (m, 1H), 1.14 0.84 (m, 3H), 0.84-0.54 (m, 3H);

(179) .sup.13C NMR (100 MHz, CDCl.sub.3) 161.56, 147.97, 122.15, 121.03, 77.40, 35.04, 19.40, 16.20;

(180) HPLC: after acylation, CHIRAL OJ column, Hexanes:IPA=97:03, UV detection at 254 nm, Flow rate 0.3 ml/min, tR (minor isomer)=22.02 min, tR (major isomer)=25.35 min, 71% ee;

(181) [α].sub.D=+28.6 (c 0.5, EtOH).

23. Preparation of Compound 23: (S)-1-(pyridine-2-yl)but-3-en-1-ol

(182) ##STR00033##

(183) The same procedure as for Compound 1 was conducted, with the exception of using racemic 1-(pyridine-2-yl)but-3-en-1-ol (150 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 23 (57 mg, 0.382 mmol, 68% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 23, as follows:

(184) HRMS (EI) calcd for C.sub.29H.sub.22BNO.sub.3 [M].sup.+: 443.1693, found: 443.1691;

(185) .sup.1H NMR (400 MHz, CDCl.sub.3) 8.38-8.31 (m, 2H), 7.58-7.48 (m, 2H), 7.26-7.22 (m, 1H), 7.06-6.98 (m, 2H), 5.78-5.63 (m, 2H), 5.00 4.92 (m, 1H), 4.96-4.89 (m, 3H), 4.85-4.73 (m, 2H), 4.73-4.66 (m, 2H), 2.56-2.45 (m, 2H), 2.43-2.32 (m, 2H);

(186) .sup.13C NMR (100 MHz, CDCl.sub.3) 162.26, 162.22, 148.11, 136.64, 134.27, 122.18, 120.43, 117.61, 117.59, 117.57, 72.73, 42.61, 42.58.

(187) HPLC: after acylation, with CHIRAL OD, Hexanes:IPA=90:10, UV detection at 254 nm, Flow rate 0.5 ml/min, tR (major isomer)=9.92 min, tR (major isomer)=13.02 min, 68% ee;

(188) [α].sub.D=−14.8 (c 1.5, CHCl.sub.3).

23-1. Preparation of Compound 23: (S)-1-(pyridine-2-yl)but-3-en-1-ol

(189) The same procedure as for Compound 1 was conducted, with the exception of using 0.45 equivalents of (R)-3,3′-(CONEt.sub.2).sub.2-binol (218 mg) instead of (R)-binol (128 mg, 0.45 mmol), to prepare Compound 23 at a yield of 39% and an ee of 86%.

(190) [α].sub.DH=−18.9 (c 1.0, CHCl.sub.3).

24. Preparation of Compound 24: (S)-1-phenyl-2-(piperidin-1-yl)ethan-1-ol

(191) ##STR00034##

(192) The same procedure as for Compound 1 was conducted, with the exception of using racemic 1-phenyl-2-(piperidin-1-yl)ethan-1-ol (205 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 24 (76.5 mg, 0.37 mmol, 77% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 24, as follows:

(193) HRMS (EI) calcd for C.sub.33H.sub.30BNO.sub.3 [M].sup.+: 499.2319, found: 499.2323;

(194) .sup.1H NMR (500 MHz, CDCl.sub.3) 7.43-7.15 (m, 5H), 4.78-4.65 (m, 1H), 3.29 (s, 1H), 2.75-2.71 (m, 1H), 2.55-2.48 (m, 1H), 2.47-2.38 (m, 3H), 1.75-1.57 (m, 4H), 1.53-1.47 (m, 2H), 1.30-1.27 (m, 1H), 0.98-0.83 (m, 1H);

(195) .sup.13C NMR (126 MHz, CDCl.sub.3) 142.45, 128.32, 127.39, 125.87, 68.67, 66.93, 54.47, 26.12, 24.27;

(196) HPLC: CHIRAL OD column, Hexanes:IPA:DEA=95:05:0.5, UV detection at 254 nm, Flow rate 1.0 ml/min, tR (minor isomer)=11.66 min, tR (major isomer)=15.47 min, 77% ee;

(197) [α].sub.D=+30.4 (c 1.25, EtOH).

25. Preparation of Compound 25: (S)-2-morpholino-1-phenylethan-1-ol

(198) ##STR00035##

(199) The same procedure as for Compound 1 was conducted, with the exception of using racemic 2-morpholino-1-phenylethan-1-ol (207.5 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 25 (85 mg, 0.38 mmol, 91% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 25, as follows:

(200) HRMS (EI) calcd for C.sub.32H.sub.28BNO.sub.4 [M].sup.+: 501.2111, found: 501.2117;

(201) .sup.1H NMR (500 MHz, CDCl.sub.3) 7.43-7.34 (m, 4H), 7.34-7.27 (m, 1H), 4.82-4.75 (m, 1H), 3.84-3.72 (m, 4H), 2.81-2.73 (m, 2H), 2.60 2.54 (m, 1H), 2.54-2.45 (m, 3H);

(202) .sup.13C NMR (126 MHz, CDCl.sub.3) 141.88, 128.41, 127.61, 125.86, 68.60, 68.17, 67.05, 66.71;

(203) HPLC: CHIRAL OD C.sub.18 Column (5 m, 4.6 150 mm) (Hexanes:IPA:DEA=95:05:0.5, UV detection at 254 nm, Flow rate 1.0 ml/min, tR (major isomer)=21.81 min, tR (major isomer)=29.29 min, 91% ee;

(204) [α].sub.D=+45.3 (c 0.9, EtOH).

26. Preparation of Compound 26: (R)-1-(phenyl(pyrrolidin-1-yl)methyl)naphthalen-2-ol

(205) ##STR00036##

(206) The same procedure as for Compound 1 was conducted, with the exception of using racemic 1-(phenyl(pyrrolidin-1-yl)methyl)naphthalen-2-ol (303.5 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 26 (96 mg, 0.31 mmol, 78% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 26, as follows:

(207) HRMS (EI) calculated for C.sub.41H.sub.32BNO.sub.3 [M].sup.+: 597.2475, found: 597.2451;

(208) .sup.1H NMR (300 MHz, CDCl.sub.3), δ 7.87 (d, J=8.6 Hz, 1H), 7.77-7.53 (m, 4H), 7.43-7.32 (m, 1H), 7.31-7.11 (m, 5H), 5.13 (s, 1H), 3.56-2.91 (br s, 1H), 2.91-2.05 (m, 3H), 1.98-1.61 (m, 4H);

(209) .sup.13C NMR (75 MHz, CDCl.sub.3), δ 155.9, 141.3, 132, 129.4, 128.9, 128.8, 128.6, 128.5, 127.9, 126.5, 122.4, 121.2, 119.9, 116.6, 70.8, 53.5, 23;

(210) HPLC: CHIRAL OD column, hexanes:IPA=90:10, UV detection at 254 nm, Flow rate 1.0 ml/min, tR (major isomer)=5.26 min, tR (minor isomer)=5.85 min, 78% ee;

(211) [α].sub.D=−69.8 (c 1.5, CHCl.sub.3).

27. Preparation of Compound 27: (R)-1-(morpholino(phenyl)methyl)naphthalen-2-ol

(212) ##STR00037##

(213) The same procedure as for Compound 1 was conducted, with the exception of using racemic 1-(morpholino(phenyl)methyl)naphthalen-2-ol (320 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 27 (100 mg, 0.31 mmol, 99% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 27, as follows:

(214) HRMS (EI) calculated for C.sub.41H.sub.32BNO.sub.4 [M].sup.+: 613.2424, found: 597.2451;

(215) .sup.1H NMR (400 MHz, CDCl.sub.3) 13.15 (s, 1H), 7.88 (d, J=8.6 Hz, 1H), 7.77-7.68 (m, 2H), 7.64-7.57 (m, 2H), 7.46-7.37 (m, 1H), 7.36-7.21 (m, 5H), 7.18 (d, J=8.8 Hz, 1H), 5.16 (s, 1H), 4.08 3.77 (m, 3H), 3.77-3.48 (m, 1H), 3.38-2.98 (m, 1H), 2.61-2.40 (m, 3H);

(216) .sup.13C NMR (100 MHz, CDCl.sub.3) 154.79, 138.68, 132.38, 129.81, 128.95, 128.85, 128.24, 126.59, 122.65, 121.06, 119.82, 115.14, 77.36, 77.04, 76.73, 72.06, 66.93; HPLC: CHIRAL OD-H Column, Hexanes:IPA=90:10, UV wavelength at 254 nm, Flow rate=1.0 ml/min, tR (major isomer)=9.48 min, tR (minor isomer)=10.82 min, 99% ee;

(217) [α].sub.D=−102.4 (c 1.25, CHCl.sub.3).

28. Preparation of Compound 28: (S)-3-(dimethylamino)-1-(thiophen-2-yl)propan-1-ol

(218) ##STR00038##

(219) The same procedure as for Compound 1 was conducted, with the exception of using racemic 3-(dimethylamino)-1-(thiophen-2-yl)propan-1-ol (186 mg, 1.0 mmol) and (R)-3,3′-(CONEt.sub.2).sub.2-binol (218 mg, 0.45 mmol) instead of racemic (4-chlorophenyl) (pyridine-2-yl)methanol (219.7 mg, 1.0 mmol) and (R)-binol (128 mg, 0.45 mmol), respectively, to prepare Compound 28 (65 mg, 0.35 mmol, 62% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 28, as follows:

(220) HRMS (EI) calculated for C.sub.39H.sub.44BN.sub.3O.sub.5S [M].sup.+: 677.3095, found: 677.3097;

(221) .sup.1H NMR (500 Hz, CDCl.sub.3) δ 7.21 (d, J=4.8 Hz, 1H), 6.98-6.80 (m, 2H), 5.19 (dd, J=4.0 Hz, 8.0 Hz, 1H), 2.70-2.50 (m, 2H), 2.29 (s, 6H), 2.00-1.88 (m, 2H);

(222) .sup.13C NMR (126 MHz, CDCl.sub.3) δ 150.80, 126.45, 123.85, 122.56, 67.46, 56.02, 45.24, 36.94;

(223) HPLC: Chiralcel AD-H column, hexane:isopropanol:diethylamine=97:2:0.1, Flow rate=0.5 ml/min, UV detection at 254 nm, tR (major isomer)=25.65 min, tR (minor isomer)=27.94 min, 62% ee;

(224) [α].sub.D=−4.6 (c 0.5, MeOH).

29. Preparation of Compound 29: (S)-3-(dimethylamino)-1-phenylpropan-1-ol

(225) ##STR00039##

(226) The same procedure as for Compound 28 was conducted, with the exception of using racemic 3-(dimethylamino)-1-phenylpropan-1-ol (180 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 29 (60 mg, 0.33 mmol, 81% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 29, as follows:

(227) HRMS (EI) calculated for C.sub.41H.sub.46BN.sub.3O.sub.5 [M].sup.+: 671.3531, found: 671.3537;

(228) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.39 (m, 4H), 7.24 (t, 1H, J=7.08 Hz), 5.26 (s, 1H), 4.94 (q, J=4.12 Hz, 1H), 2.63 (m, 1H), 2.43 (m, 1H), 2.29 (s, 6H), 1.84 (m, 2H);

(229) .sup.13C NMR (100 MHz, CDCl.sub.3): 145.13, 128.12, 126.72, 125.51, 75.50, 58.30, 45.24, 34.57;

(230) HPLC: Chiralcel AD-H column, hexane:isopropanol:diethylamine=95:5:0.2, UV detection at 254 nm, Flow rate 0.5 ml/min, tR (major isomer)=13.33 min, tR (minor isomer)=18.47 min, 81% ee;

(231) [α].sub.D=−25.6 (c 0.5, MeOH).

30. Preparation of Compound 30: (S)-3-(dimethylamino)-3-phenylpropan-1-ol

(232) ##STR00040##

(233) The same procedure as for Compound 1 was conducted, with the exception of using racemic 3-(dimethylamino)-3-phenylpropan-1-ol (180 mg, 1.0 mmol) instead of racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), to prepare Compound 30 (58 mg, 0.32 mmol, 95% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 30, as follows:

(234) HRMS (EI) calculated for C.sub.31H.sub.28BNO.sub.3 [M].sup.+: 473.2162, found: 473.2157;

(235) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.32 (m, 5H), 5.14 (brs, 1H), 3.85 (m, 2H), 3.72 (m, 1H), 2.40 (m, 1H), 2.19 (s, 6H), 1.74 (m, 1H);

(236) .sup.13C NMR (100 MHz, CDCl.sub.3): 136.1, 129.3, 128.2, 127.9, 127.0, 71.0, 63.3, 41, 7, 32.2;

(237) HPLC: Chiralcel OJ column, hexane:isopropanol:diethylamine=90:10:0.1, UV detection at 254 nm, Flow rate 1.0 ml/min, tR (major isomer)=12.10 min, tR (minor isomer)=19.71 min, 94% ee;

(238) [α].sub.D=+38.5 (c 1.0, CHCl.sub.3).

31. Preparation of Compound 31: (S)-1-(2-(dimethylamino)-1-(4-methoxyphenyl)ethyl)cyclohexanol

(239) ##STR00041##

(240) The same procedure as for Compound 1 was conducted, with the exception of using isopropanol (6 ml), racemic 1-(2-(dimethylamino)-1-(4-methoxyphenyl)ethyl)cyclohexanol (277.4 mg, 1.0 mmol), and (R)-3,3′-(CONEt.sub.2).sub.2-binol (218 mg, 0.45 mmol) instead of acetonitrile (6 ml), racemic (4-chlorophenyl)(pyridine-2-yl)methanol (219.7 mg, 1.0 mmol), and (R)-binol (128 mg, 0.45 mmol), respectively, to prepare Compound 31 (86 mg, 0.31 mmol, 71% ee). HRMS data for the amino alcohol-boron-binol complex are given, together with physicochemical properties of Compound 31, as follows:

(241) HRMS (EI) calculated for C.sub.47H.sub.56BN.sub.3O.sub.6 [M].sup.+: 769.4262, found: 769.4260;

(242) .sup.1H NMR (500 MHz, Acetonitrile-d.sub.3) δ.sub.H 7.13 (d, J=8.3 Hz, 2H), 6.86 (d, J=8.3 Hz, 2H), 3.78 (s, 3H), 3.25 (t, J=12.0 Hz, 1H), 2.93 (dd, J=11.3, 4.5 Hz, 1H), 2.28 (s, 7H), 1.65 (pt, J=12.8, 3.6 Hz, 3H), 1.57-1.44 (m, 3H), 1.35 (dt, J=12.9, 3.8 Hz, 1H), 1.25 (td, J=13.4, 4.1 Hz, 1H), 1.02-0.83 (m, 2H) ppm;

(243) HPLC: Chiral AD-H, 3% IPA in Hexanes, 0.1% TEA, Flow rate 0.4 ml/min, UV detection at 274 nm, tR=13.97 is =16.13 (Major), 71% ee; [α].sub.D=+28.4 (c 1.05, EtOH).

Comparative Example 1: Preparation of Comparative Optically Active Amino Alcohol Derivatives

1. Preparation of Comparative Compound 1: (S)-(4-chlorophenyl)(pyridine-2-yl)methanol

(244) The same procedure as for Compound 1 was conducted, with the exception of using 1 equivalent of B(OH).sub.3 and 1 equivalent of (R)-binol instead of B(OiPr).sub.3 (188 mg, 1.0 mmol) and (R)-binol (128 mg, 0.45 mmol), respectively, to prepare Comparative Compound 1 at a yield of 64% and an ee of 28%.

2. Preparation of Comparative Compound 2: (S)-(4-chlorophenyl)(pyridine-2-yl)methanol

(245) The same procedure as for Compound 1 was conducted, with the exception of using 1 equivalent of (R)-binol instead of (R)-binol (128 mg, 0.45 mmol), to prepare Comparative Compound 2 at a yield of 52% and an ee of 38% ee.

3. Preparation of Comparative Compound 3: (S)-(4-chlorophenyl)(pyridine-2-yl)methanol

(246) The same procedure as for Compound 1 was conducted, with the exception of using 1 equivalent of B(OH).sub.3 and 0.5 equivalents of (R)-binol instead of B(OiPr).sub.3 (188 mg, 1.0 mmol) and (R)-binol (128 mg, 0.45 mmol), respectively, to prepare Comparative Compound 3 at a yield of 42% and an ee of 62% ee.

4. Preparation of Comparative Compound 4: (S)-(4-chlorophenyl)(pyridine-2-yl)methanol

(247) The same procedure as for Compound 1 was conducted, with the exception of using 1 equivalent of B(OMe).sub.3 and 0.5 equivalents of (R)-binol instead of B(OiPr).sub.3 (188 mg, 1.0 mmol) and (R)-binol (128 mg, 0.45 mmol), respectively, to prepare Comparative Compound 4 at a yield of 38% and an ee of 65% ee.

5. Preparation of Comparative Compound 5: (S)-(4-chlorophenyl)(pyridine-2-yl)methanol

(248) The same procedure as for Compound 1 was conducted, with the exception of using 1 equivalent of B(OEt).sub.3 and 0.5 equivalents of (R)-binol instead of B(OiPr).sub.3 (188 mg, 1.0 mmol) and (R)-binol (128 mg, 0.45 mmol), respectively, to prepare Comparative Compound 5 at a yield of 45% and an ee of 73% ee.

6. Preparation of Comparative Compound 6: (S)-(4-chlorophenyl)(pyridine-2-yl)methanol

(249) The same procedure as for Compound 1 was conducted, with the exception of using 1 equivalent of B(OPh).sub.3 and 0.5 equivalents of (R)-binol instead of B(OiPr).sub.3 (188 mg, 1.0 mmol) and (R)-binol (128 mg, 0.45 mmol), respectively, to prepare Comparative Compound 6 at a yield of 39% and an ee of 67% ee.

7. Preparation of Comparative Compound 7: (S)-(4-chlorophenyl)(pyridine-2-yl)methanol

(250) The same procedure as for Compound 1 was conducted, with the exception of using 0.5 equivalents of (R)-3,3′-Br.sub.2-binol instead of (R)-binol (128 mg, 0.45 mmol), to prepare Comparative Compound 7 at a yield of 40% and an ee of 60% ee.

Experimental Example 1: Identification of Optical Purity

(251) Optical purities of Amino alcohol derivatives for the compounds prepared in Example 1 and Comparative Example 1 are given in Table 1, below.

(252) TABLE-US-00001 TABLE 1 Reaction Condition Optical Boron Purity Compound Compound (R)- or (S)-Binol (% ee) Example 1 - Compound 1 1 eq, B(OPr.sup.i).sub.3 98 Comparative Example 1 - Comparative Compound 1 1 eq, B(OH).sub.3 28 Comparative Example 1 - Comparative Compound 2 1 eq, B(OPr.sup.i).sub.3 38 Comparative Example 1 - Comparative Compound 3 1 eq, B(OH).sub.3 62 Comparative Example 1 - Comparative Compound 4 1 eq, B(OMe).sub.3 65 Comparative Example 1 - Comparative Compound 5 1 eq, B(OEt).sub.3 73 Comparative Example 1 - Comparative Compound 6 1 eq, B(OPh).sub.3 67 Comparative Example 1 - Comparative Compound 7 1 eq, B(OMe).sub.3 60

(253) As is understood from the data of Table 1, Compound 1, which was prepared under the condition of Example 1, is for superior in terms of optical purify to Comparative Compounds 1 to 7, which were prepared under the condition of Comparative Example 1.

(254) Accordingly, amino alcohol derivatives with high optical purity can be obtained by reacting a racemic compound with a boron compound and (R)- or (S)-binol at specific equivalents controlled according to the present disclosure.

(255) Although the preferred embodiments of the present invention have been disclosed for illustrative purposes, those skilled in the art will appreciate that various modifications, additions and substitutions are possible, without departing from the scope and spirit of the invention as disclosed in the accompanying claims.