S -Methyl Mandelate

We developed an alternative method based on the resolution of phenylglycine derivatives [22]. Accordingly, the racemic amine was reacted with a chiral auxiliary, namely the tosyl derivative of ( S)-(+)-methyl mandelate, followed by chromatographic separation of the two diastereomers formed and the subsequent hydrogenation of the separated compounds to ve the free amines with good enantiomeric excess (e.e. 94% ). 

In the region of methyl deformational modes and in the C-H stretching region, the VCD of a-phe-nylethylamine, a-phenylethanol, a-phenylethyliso-cyanate, p-bromophenylethylamine and (S)-methyl mandelate [18] was examined. The bands near 1450cm i were explained by interaction of the CH3 deformational mode with an energetically neighbouring phenyl vibration. 

With 1-phenylethanol, 1-phenylethanethiol, 1-chloro-l-phenylethane, D-a-phenylglycine-N-d3 and (S)-methyl mandelate, the VCD of the methine stretching vibration is enhanced by ring currents. For methyl mandelate, a very large value of A = 5 x 10" is found for the O-H stretching vibration. 

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 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%... 

The results collected in Table 5 suggest that hydrocarbon residues, especially aromatic groups, in the solvent are strongly responsible for the interaction with cis-(1+4). The position of the largest hydrocarbon residue apparently determines whether P- or M-[6]-helicene will be formed in excess. Replacement of the methyl group in (S)-ethyl lactate (b) by a phenyl group giving (S)-ethyl mandelate (d), increases the optical yield fivefold. 

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. 

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. 

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). ... 

The tracer pulse method was also used by Bliimel et al. [112] to determine the binary isotherms of the enantiomers of l-phenoxy-2-propanol on Chiralcel OD, by Lindholm et al. [113] to determine the binary isotherms of methyl-mandelate on Chiral AGP, and by Mihlbachler et al. [1] to determine those of the enantiomers of Troger s base on Chiralpak AD. In this last case, an imusual isotherm was obtained, illustrated in Figure 4.28. The adsorption of the more retained (+) enantiomer is not competitive the amoimt adsorbed by the chiral stationary phase at equilibrium with a constant concentration of the (+) enantiomer is independent of the concentration of the (-) enantiomer. On the other hand, the adsorption of the less retained enantiomer is cooperative the amoimt of this (-) enantiomer adsorbed by the CSP at equilibrium with a constant concentration of this enantiomer increases with increasing concentration of the (+) enantiomer. The isotherm data are best accounted for by an isotherm model derived assuming multilayer adsorption. 

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. " ... 

Other than the auxiliary reagents described by Riguera s group in the preceding pages, very few papers have been devoted to the determination by NMR of absolute configuration of carboxylic acids. In one such example, however, (5)-methyl mandelate was tested as a chiral auxiliary with racemic and... 

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)-(+)-... 

HPLC/API (S)-Phenylalanine (S)-Mandelic acid methyl ester 0.85 376... 

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. 

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