R-methyl mandelate

Methyl (R)-(-)-mandelate or (R)-(-)-methyl mandelate (Aldrich catalog name) Mandelic acid, methyl ester, (R)- or mandelic acid, methyl ester (R)-(-)- (8) Benzeneacetic acid, a-hydroxy-, methyl ester, (R)- (9) (20698-91-2)... 

R)-(-)-methyl lactate (R)-(-)-methyl mandelate 9-MeO-10,11 -dihydrocinchonidine methyl acetoacetate... 

R)- and (,S )-1.1,2-Triphenyl-l,2-ethancdiol which are reliable and useful chiral auxiliary groups (see Section 1.3.4.2.2.3.) also perform ami-sclcctive aldol additions with remarkable induced stereoselectivity72. The (/7)-diastercomer, readily available from (7 )-methyl mandelate (2-hy-droxy-2-phcnylaeetate) and phenylmagnesium bromide in a 71 % yield, is esterified to give the chiral propanoate which is converted into the O-silyl protected ester by deprotonation, silylation, and subsequent hydrolysis. When the protected ester is deprotonated with lithium cyclohexyliso-propylamide, transmetalated by the addition of dichloro(dicyclopentadienyl)zirconium, and finally reacted with aldehydes, predominantly twm -diastereomers 15 result. For different aldehydes, the ratio of 15 to the total amount of the syn-diastereomers is between 88 12 and 98 2 while the chemical yields are 71 -90%. Furthermore, high induced stereoselectivity is obtained the diastereomeric ratios of ami-15/anti-16 arc between 95 5 and >98 2. 

The chiral acetate reagent is readily prepared from methyl mandelate [methyl (A)-hydroxy-phenyl acetate] which is first converted by treatment with phcnylmagnesium bromide into the triphenylglycol783, c (see Section 1.3.4.2.2.2.) and subsequently transformed into the acetate by reaction with acetyl chloride in the presence of pyridine. Thereby, the secondary hydroxyl group of the glycol is esterified exclusively. Both enantiomers of the reagent are readily accessible since both (R)- and (5)-hydroxyphenylacelic acid (mandelic acids) arc industrial products. 

As shown in Scheme 9, various organic compounds can act as a chiral initiator of asymmetric auto catalysis. 2-Methylpyrimidine-5-carbaldehyde 9 was subjected to the addition of z-Pr2Zn in the presence of chiral butan-2-ol, methyl mandelate and a carboxylic acid [74], When the chiral alcohol, (S)-butan-2-ol with ca. 0.1% ee was used as a chiral initiator of asymmetric autocatalysis, (S)-pyrimidyl alkanol 10 with 73% ee was obtained. In contrast, (,R)-butan-2-ol with 0.1% ee induced the production of (A)-10 with 76% ee. In the same manner, methyl mandelate (ca. 0.05% ee) and a chiral carboxylic acid (ca. 0.1% ee) can act as a chiral initiator of asymmetric autocatalysis, therefore the S- and IC enantiomers of methyl mandelate and carboxylic acid induce the formation of (R)- and (S)-alkanol 10, respectively. Chiral propylene oxide (2% ee) and styrene oxide (2% ee) also induce the imbalance of ee in initially forming the zinc alkoxide of the pyrimidyl alkanol in the addition reaction of z-Pr2Zn to pyrimidine-5-carbaldehyde 11 [75]. Further consecutive reactions enable the amplification of ee to produce the highly enantiomerically enriched alkanol 12 (up to 96% ee) with the corresponding... 

Preparative Methods (7 )-l,l,2-triphenylethane-l,2-diol [(7 )-(1)] is easily available from commercial (R)-Mandelic Acid, which is first esterified to give methyl mandelate and then treated with Phenylmagnesium Bromide (3.5 equiv). In an analogous way, (S)-(l) is accessible from (S)-mandelic acid, which is also commercially available (eq 1). ... 

Reaction with chiral I,3-dioxolan-4-ones. In contrast to RLi and R2CuLi, which react with the carbonyl group of chiral l,3-dioxolan-4-ones (1), prepared from (R)- or (S)-mandelic acid and an aldehyde, RCu(MgBr2) or R2CuMgBr react with the diox-olanone 1 to provide ethers of methyl mandelate (2) in 90-94% ee. Removal of the... 

It is highly desirable that chiral a-unsubstituted enolates should be available by simple methods from enantiomerically pure starting materials that are inexpensive and readily accessible in both enantiomeric forms. This postulate seems to be fulfilled to a reasonable extent by (R)- and (S)-2-hydroxy-l,l,2-triphenylethyl acetate 83 ( HYTRA ) [53, 128, 129]. It is readily prepared from methyl mandelate vhich is first converted into triphenylglycol 82 and subsequently converted into the acetic ester 83 by treatment vith acetyl chloride (Eq. (34)). Both enantiomers of the reagent are readily accessible, because both (R)- and (S)-mandelic acid are industrial products [130]. Diol 82 and acetate 83 are commercially available. 

The pro-(R) and pro-(S) hydrogen atoms in methylene groups of a-deuterated carboxylic acids can be distinguished in derivatives with methyl mandelate 37. The conformational preference and shielding of the phenyl ring of 37 is used to assign the positions of deuterium substitution and absolute configuration. " ... 

R)-(+)-1,1,2-Triphenyl-1,2-ethanediol is available from methyl3 and ethyl4 (R)-(-)-mandelate by treatment with phenylmagnesium bromide. The synthesis of (R)-(+)-2-hydroxy-1,2,2-triphenylethyl acetate [(R)-HYTRA] has been reported previously by the submitters.5 6 (S)-(-)-2-Hydroxy-1,2,2-triphenylethyl acetate is available according to this procedure starting from the enantiomeric methyl (S)-(+)-mandelate or (S)-(+)-... 

Grunblatt E, Mandel S, Maor G, Youdim MB. 2001. Gene e]q>ression analysis in N-methyl-4-phenyl- 1,2,3,6-tetrahydro-pyridine mice model of Parkinson s disease using cDNA microarray effect of R-apomorphine. J Neurochem 78 1. 

Polymerization of the bulky monomer chloral yields an optically active product when one uses a chiral initiator, e.g., lithium salts of methyl (+)- or (—)-mandelate or (R)- or (S)-octanoate [Corley et al., 1988 Jaycox and Vogl, 1990 Qin et al., 1995 Vogl, 2000], The chiral initiator forces propagation to proceed to form an excess of one of the two enantiomeric helices. The same driving force has been observed in the polymerization of triphenyl-methyl methacrylate at —78°C in toluene by initiating polymerization with a chiral complex formed from an achiral initiator such as n-butyllithium and an optically active amine such as (+)-l-(2-pyrrolidinylmethyl)pyrrolidine [Isobe et al., 2001b Nakano and Okamoto, 2000 Nakano et al., 2001]. Such polymerizations that proceed in an unsymmetrical manner to form an excess of one enantiomer are referred to as asymmetric polymerizations [Hatada et al., 2002]. Asymmetric polymerization has also been observed in the radical... 

One Sanofi synthesis of enantiomerically pure (-i-)-clopidogrel (2) utilized optically pure (R)-(2-chloro-phenyl)-hydroxy-acetic acid (20), a mandelic acid derivative, available from a chiral pool. After formation of methyl ester 21, tosylation of (/ )-21 using toluene sulfonyl chloride led to a-tolenesulfonate ester 22. Subsequently, the Sn2 displacement of 22 with thieno[3,2-c]pyridine (8) then constructed (-i-)-clopidogrel (2). Another Sanofi synthesis of enantiomerically pure (-i-)-clopidogrel (2) took advantage of resolution of racemic a-amino acid 23 to access (S)-23. The methyl ester 24 was prepared by treatment of (S)-23 with thionyl chloride and methanol. Subsequent Sn2 displacement of (2-thienyl)-ethyl para-toluene-sulfonate (25) assembled amine 26. 

Enantioselective aldol condensation. Masamtinc et al. have prepared optically pure /Miydroxy-a-methyl carboxylic acids by aldol condensation with the (S)- and (RHsomers of the ethyl ketone I, prepared in three steps from commercially available (S)- and (R>mandelic acid. For example, (SH is converted into the (Z)-boron cnolatc (2), which condenses with propionaldehyde to form a single aldol... 

R)-(+)-2-Hydroxy-l, 2,2-triphenylethyl acetate (1). Preparation from methyl (R)-( —)-mandelate ... 

Methyl (R)- and (S)-mandelate, C HsCH(OH)COOCH3. This hydroxy acid is a aseful chiral auxiliary because it is available commercially in both enantiomeric forms and is removable by hydrogenolysis. 

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