Methyl 5- -mandelate

Maltol — see Pyran-4-one, 3-hydroxy-2-methyl-Maltol, ethyl — see Pyran-4-one, 3-ethoxy-2-methyl-Maltol, methyl — see Pyran-4-one, 3-methoxy-2-methyl-Mandelic acid ethyl ester, 1, 310-311 Manganaindene reactions, 1, 671 Mannich bases dehydro... 

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. 

The secondary benzylic alcohol l-phenylethan-l,2-diol requires 20 hours of treatment at room temperature to produce a 64% yield of 2-phenylethanol (Eq. 43).137 Under the same conditions, methyl mandelate fails to undergo reduction, presumably because of the greater carbocation-destabilizing effect of a neighboring carboalkoxy compared to a hydroxymethyl group (Eq. 43).137... 

Molten methyl mandelate dissolves readily in diethyl ether. 

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)... 

The use of surface bound triflate ions has been exploited by Raja et al. to immobilize the complexes [Rh(COD) fSj-(-i-)-PMP ], [Pd(allyl) fSj-(-i-)-PMP ], [Rh(COD) fSj-(-)-AEP rand[Rh(COD) flR,2Rj-(-t)-DED ]"in the pores of silicas possessing various pore sizes with narrow distributions [128]. These constrained chiral catalysts were then tested for the asymmetric hydrogenation of methyl ben-zoylformate to its corresponding methyl mandelate (40°C, methanol, 2 MPa H2). In the homogenous form, only the catalysts [Rh(COD) fSj-(-i-)-PMP ], [Pd(allyl) (Sj-(-i-)-PMP ] exhibit any signiflcant e.e.s under the reaction conditions (53%... 

Aminolysis with butylamine, rather than hydrolysis or transesterification, has been employed in the kinetic resolution of methyl mandelate (Figure 10.13) [123]. Enanhoselectivities in the kinetic resolution of mandelic acid via transesterification are generally low. Aminolysis (or ammoniolysis) may improve the resolution, as has been shown in some cases [124, 125], presumably by a shift of the ratedetermining step. Resolution with CaLB in conventional media afforded quite modest E ratios, which became near-quantitative when 10% [BMIm][BF4] was added to the medium [122]. 

The enantiorecognition of methyl mandelate (Figure 10.14) in enantioselective acylation with vinyl acetate is often modest Itoh et al. studied this latter reaction with immobilized PcL in [BMIm][PF,s] and found that the E-ratio varied from 10 to >250, depending on the carrier [128]. The best rate and enantioselectivity were obtained with PcL immobilized on a methacryloxypropyl-modified macroporous S BA-15 silica. 

The original Sanofi synthesis of ( )-clopidogrel (2) began with the formation of the methyl ester 13. Thus methyl mandelate 13 was prepared by refluxing chlorinated mandelic acid 12 with methanol in the presence of concentrated HCl. Chlorination of... 

S-(0-Methyl)mandelic acid chloride was prepared (14-h reflux in 5 mL of benzene) from the S-(0-methyl)mandelic acid (0.33 g, 2.0 mmol) and oxalyl chloride (0.34 mL, 4.0 mmol). The chloride was added to a solution of 3 (0.56 g, 2.0 mmol) and dry pyridine (0.33 mL, 4.0 mmol) in dry toluene (20 mL) at — 10°C. The mixture was then allowed to attain 0°C. After 14 h, toluene was added, and the mixture was washed with water (20 mL). Toluene solution was dried (MgS04) and concentrated to dryness to yield 4 (0.84, 98%), which was used in the next step without purification. 

Methyl phenoxyacetate Ethyl phenoxyacetate Ethyl ( + )-mandelate Methyl ( + )-mandelate... 

Lipkowitz and Stoehr [114] studied the binding of the enantiomers of methyl mandelate under buffered and unbuffered conditions at different temperatures. The authors reported that the stereodifferentiating binding energies for the... 

Mravik, A., Bocskei, Zs., Katona, Z., Markovits, I., Pokol, Gy., Menyhard, D.K., and Fogassy, E. A new optical resolution method coordinative resolution of mandelic acid esters. The crystal structure of calcium hydrogen (2R,3R)-0,0 -dibenzoyltartrate-(2i )-methyl mandelate, J. Chem. Soc. Chem. Commun. 1996, 1983. 

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... 

Enantiomer separation of various compounds such as barbituric acids, benzoin, MTH-proline, glutethimide, a-methyl-oc-phenyl-succinimide, y-phenyl-y-butyrolac-tone, methyl-mandelate, l-(2-naphthyl)ethanol, mecoprop methyl, diclofop methyl and fenoxaprop methyl by pressure supported CEC on a permethyl-P-cyclodextrin modified stationary phase was described by Wistuba and Schurig [42-44]. Three different separation beds were used (i) permethyl-P-cyclodextrin was covalently attached via a thioether to silica (Chira-Dex-silica) [42], permethyl-P-cyclodextrin was linked to a dimethylpolysiloxane and thermally immobilized (ii) on silica (Chirasil-Dex-silica) [43] or (iii) on a silica monolith (Chirasil-Dex-monolith) [44], respectively. 

Barbiturates (mephobarbital, hexobarbital, pentobarbital, l-methyl-5-(2-propyl)-5-(n-propyl)barbituric acid, 5-ethyl-1 -methyl-5-(n-propyl) barbituric acid), benzoin, a-methyl-a-phenylsuccinimide, gluthethimide, methylthiohy-dantoin-proline, methyl mandelate... 

Corey exploited the remarkable configurational stability of cyclopropyllithiums in his synthesis of hybridalactone. The stannane 28 was made by Simmons-Smith cyclopropanation of the allylic alcohol 27 and resolved by formation of an O-methyl mandelate ester. Transmetallation of 29 with 2 equiv. BuLi gave an organolithium which retained its stereochemistry even in THF over a period of 3 h at 0 °C, finally adding to 31 to give 32. 

Radical mechanisms account for the stoichiometry for reduction of triketohydrindane by N(5)-ethyldihydroflavin and reduction of triphenylmethyl carbonium ion species by dihydroflavin, (24). One-electron reduction of quinone by N(5)-ethyldihydroflavin also has been shown. These results are not surprising since the substrates and flavin support reasonably stable radical states. Radical species also can be established as intermediates in the oxidation of 9-hydroxyfluorene and methyl mandelate by Flox (Equations 28 and 29, respectively). The reactions of Equations 28 and 29 are facile when carried out in... 

H]propionates derived from dl-, d- and L-alanine have been esterified with (i )-methyl mandelate using 4-dimethylaminopyridine (DMAP) and dicyclohexylcarbo-diimide (DCCD) in 47% yield (equation 36) and their 2H-NMR spectra determined. 

---