Menthyl mandelates

Optically active substances are preferentially adsorbed by some optically active adsorbent. Thus Broadly and Easty (1951) found wool and casein to adsorb (+) mandelic acid from its aqueous solution. Some workers also successfully carried out resolution without using an active adsorbent. The alumina was found to be suitable for resolving diastereoisomers of (-) menthyl ( ) mandelate. 

Further examples of alkylation of (l/ )-menthyl mandelate are shown in the following table ... 

Reduction of the a-keto ester of an optically active alcohol, followed by hydrolysis of the a-hydroxy ester which results, yields an optically active a-hydroxy acid. Sixty years ago, for example, McKenzie (1904) reduced optically active (—)-menthyl phenyl-glyoxylate with aluminum amalgam in moist ether and obtained unequal amounts of diastereomeric (—)-menthyl mandelates. Saponification, however, gave racemic mandelic acid. Later work (McKenzie and Humphries, 1909) showed that racemization could be avoided by acetylation of the intermediate mandelate before saponification, and that reduction of (—)-menthyl phenylgly-oxylate produced mandelic acid having an excess of the R- —) enantiomer [Eq. (5)]. 

Hydroxy-acids.—A full report has been published on the preparation of chiral a-hydroxy-acids in optical yields of up to 98% from a, -unsaturated acid chlorides by sequential N-acylation of an optically pure a-amino-acid, bromo-lactonization, dehydrobromination, and hydrolysis " (2, 23). Enolates of /-menthyl mandelate can be alkylated in ca. 50% yield with typical enantiomeric excesses of less than 40%, An elegant use of the prophos ligands in rhodium(i)-catalysed asymmetric hydrogenation (see 3,322) is in the preparation of all twelve isomers of chiral methyl chiral lactic acid the method is illustrated for one isomer in Scheme 5. The other isomers are obtained by changing the order of introduction of H, D, and T and the chirality (i.e. R or S) of the prophos ligand. 

The result of Pezold and Shriner may instructively be compared with the work of Marckwald and McKenzie on the differential rates of saponification of the (—)-menthyl mandelates, and it would be interesting to determine whether the production of optical activity depends here also upon incomplete asymmetric decomposition of the diastereoisomerides of IV. A positive result here would throw further light on the precise reaction mechanism. 

Mandelic acid with a 13 - 20 % enantiomeric excess of the (R)-isomer has been obtained from reduction of phenylglycolic acid in aqueous alcohol buffers containing strychnine in low concentration. The optical yield depends upon pH and is highest (20 - 24 %) at pH 0 or 9.2 and at low current density. In the pH range 2-4, the optical yield drops to 2-8% [42]. The higher result compares well with the maximum value of 20% excess R-isomer found from reduction of (-)-menthyl phenylglycolate in aqueous buffers where the (-)-menthyl ester is the only chiral reagent present [43 ]. 

The (17 )-menthyl ester of mandelic acid 8 has been deprotonated to form the enediolate 9 which was preferentially alkylated to give the (7 )-product 10 in 32% yield and with 50% diastereoselectivity116. 

Frankland and Price 17 were the first to attempt the resolution of alcohols (and acids) by fractional crystallization of their solid esters. The isomeric solid esters formed from Z-s-butylcarbinol and di-dibenzoyl-glyceric acid failed to separate on crystallization the corresponding di-alcohol-i-acid ester was liquid. Marckwald and McKenzie 18-19 effected partial resolutions of dl-mandelic acid and related acids with 1-menthol and d-bomeol, and of di-2-octanol with d-tartaric acid, but did not develop a satisfactory method for resolving alcohols. Later investigators, however, have employed the following resolving agents in several more or less successful resolutions of certain alcohols (a) i-menthyl isocyanate, (6) d-camphoric acid, (c) d- or i-mandelic acid, (d) d- or... 

The principles outlined above were allied by Marckwald and McKenzie 18 for the partial resolution of a racemic acid with an active alcohol. Thus When df-mandelic acid was heated with less than one equivalent of 1-menthol, the resulting ester contained somewhat more J-menthyl-d-mandelate than f-menthyl-L-mandelate and the unesterified acid contained a corresponding excess of i-mandelic acid. Also, when a mixture of equal amounts of the two diastereoisomeric esters was partially hydrolyzed, the regenerated acid and that still combined in the residual ester contained unequal amounts of the two antipodes. The process has been extended to the resolution of acids and amines through the formation and hydrolysis of amides.89... 

Further papers of interest in the bicyclo[2,2,l]heptane series include the hydrolysis of (—)-menthyl and (+)-bornyl mandelates,296 dehalogenation of 2,2-dimethylnorbornane-3-spiro-r-(2, 2 -dibromocyclopropane),297 the sodium... 

Photocyclization using circular polarized light yielded dihydro[5]helicene in a small enantiomeric excess (ee = 3 %). Attempts were also made to enantioselectively synthesize helicenes using chiral solvents as well as cholesteric liquid crystals Excellent enantiomeric excesses (up to 98%) were obtained through temporary introduction of optically active residues like mandelic acid, lactic acid derivatives and (—)-menthyl esters... 

As, for instance, strychnine racemate, a compound of racemic acid with the optically active strychnine. This would be resolved into strychnine f-tartrate and strychnine /-tartrate, which are not enantiomorphous forms. This behaviour has been investigated in the case of the /-menthyl ester of the mandelic acids (Findlay and Hickmans,/. Chem. Soc, 1907, 91, 905. See also H. Dutilh, Proc. K, Akad, Wetensch, Amsterdam 1909, 12, 393). 

Double asymmetric reduction was observed in the reduction of (-)-menthyl phenylglyoxilate into (/ )-(-)-mandelate on a Hg cathode with an ee of 20.6% and in the diastereoselective reduction of S)- -)-N- alpha-me-thylbenzyl)benzoylformamide into the (7 ,iS)-diastereomer with an ee of 12.5%... 

Another method is by kinetic resolution, in which one of the enantiomers reacts faster with a reagent than the other. An example is the resolution of R,S)-mandelic acid. The (/J)-isomer reacts faster than the (S)-isomer with (S)-menthol. Thus by taking a stoichiometric deficiency of (S)-menthol, a product mixture can be obtained containing mainly (S)-menthyl and (7 )-mandelate and a very small quantity of (S)-menthyl and (S)-mandelate (Greenstein and Winitz, 1961). 

Some years ago, these possibilities were examined [53] with (—)-menthyl benzoylformate and ethyl benzoylformate. A simple asymmetric reduction involving either (—)-menthyl benzoylformate with an acliiral agent, liAlH4(LAH)-cyclo-hexanol, process (a), or ethyl benzoylformate with a chiral reducing agent, LAH-(+)-camphor, process (b), gave (/ )-mandelic acid after hydrolysis, in relatively low optical yields (10 and 4% e.e., respectively). On the other hand, the double asymmetric reduction , process (c), resulted in 49% asymmetric synthesis. This result is more than would be anticipated on the basis of a simple additive effect. 

From the results also shown in Table 16, the stereochemical control by the (—)-menthyl group itself was found to produce predominantly ( )-menthyl (5)-mandelate (21% e.e.), an antipode of that obtained from the lithium aluminum hydride reduction. In process (b), it was shown that a counteracting asymmetric induction by the chiral catalyst of (—)-DIOP exceeded the effect of ( )-menthyl group to give the (jR)-mandelate with rather low stereoselectivity (37% e.e.). Production of the (R)-mandelate was scarcely favored in case of the asymmetric reduction of ethyl benzoyl-... 

The preparation of myo-inositol 1,4,5-triphosphate by a process involving selective formation of diastereomeric menthyl esters in a similar way to that described in Vol. 25, p. 209, ref. 59 or by resolution of racemic derivatives with R-mandelic acid or l-/-menthoxyacetyl chloride (which involves the use of a new phosphitylating agent, o-xylene AT,lV-diethylphosphoramidite) have been reported. 

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