Optically active menthyl ester

However, even the a-unsubstituted y- and -alkenyl oximes readily give the corresponding five-and six-membered cyclic nitrones when the alkene is activated by a terminal ester group. For example, the bicyclic nitrone 4 was obtained with moderate diastereoselectivity from 3 via the oxime formed in situ1. From the optically active menthyl esters 5,1 1 mixtures of diastereomer-ic nitrones 6 were obtained. 

A non-biomimetic synthesis of /J-(-)-horsfiline (57) has also been recently reported which was based on a thermal intermolecular 1,3-dipolar cycloaddition reaction as outlined in Scheme 7 [63J. The reaction of the optically active menthyl ester 67 acting as a dipolarophile, with the JV-methylazomethine ylide 68 (thermally generated in situ from sarcosine and formaldehyde) proceeded with n-facial diastereoselectivity to produce a chromatographically separable mixture of 69 and the unwanted diastereomer. Subsequent cleavage of the chiral auxiliary, followed by removal of the carboxylic acid group by the Barton radical method provided J7-(-)-horsfiline. 

The preparation of enantiomerically enriched a-ketosulphoxides 272 was also based on a kinetic resolution involving the reaction of the carbanion 273 derived from racemic aryl methyl sulphoxides with a deficiency of optically active carboxylic esters 274334, (equation 151). The degree of stereoselectivity in this reaction is strongly dependent on the nature of both the group R and the chiral residue R in 274. Thus, the a-ketosulphoxide formed in the reaction with menthyl esters had an optical yield of 1.3% for R = Et. In the... 

The double bonds in certain heterocyclic compounds, such as furans, Af-acylpyrroles and A-acylindoles are also susceptible to photoaddition of carbonyl compounds to form oxetanes (equation 106) (77JHC1777). A wide range of carbonyl compounds can be used, including quinones, a-diketones, acyl cyanides, perfluorinated aldehydes and ketones and esters. A remarkable case of asymmetric induction in oxetane formation has been reported from optically active menthyl phenylglyoxylate and 2,3-dimethyl-2-butene the oxetane product obtained after hydrolysis of the ester group had an optical purity of 53% (79AG(E)868). 

Natta, Farina and Donati (123) found that optically active menthyl ethyl ether complexed with butyl lithium initiated asymmetric polymerization of optically inactive sorbic and /9-styryl acrylic esters. This strongly suggests that monomer orientation occurs during coordination with lithium by steric interaction with the asymmetric ligand. Similarly, asymmetric polymers were obtained using optically active 2-methyl-butyl lithium wherein the asymmetric polymer chain directed the monomer orientation. 

The best way to prepare large quantities of optically active sulfoxides makes use of optically active menthyl sulfinate. By esterification of p-toluenesulflnic acid with 1-menthol, a mixture of dia-stereoisomeric menthyl sulfinates is obtained. This esterification reaction shows no particular stereoselectivity and therefore a mixture of the two diastereoisomeric esters was obtained. However, it is possible to equilibrate these diastereoisomers in acidic media and to shift the equilibrium towards the... 

Cross-aldol reactions involving the optically active keto-esters menthyl pyruvate and phenylglyoxylate and either silyl enol ethers or keten silyl acetals have been shown to result in appreciable asymmetric induction, considerably larger than that observed in the reactions of the same chiral a-keto-esters with Grignard... 

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)]. 

Hydrostannation of chiral menthyl esters of substituted acrylic acids proceeds stereoselectiveiy, providing a route to optically active alkyl-... 

Although menthyl esters, especially 19, are most often used to prepare sulfoxides, esters derived from optically active alcohols other than menthol have been prepared . Ridley and Smal prepared arenesulfmic esters of 1,2 5,6-di-O-cyclohexylidene-a-D-glucofuranose. Unfortunately, these diastereomers were oils, except for the mesityl derivative, with the major epimer having configuration R at sulfur and so they offered no advantage over the menthyl esters. Separation of the epimers by chromatography failed. 

Baldwin et al. have used the same catalyst/diazo ester combination for the synthesis of optically active deuterated phenylcyclopropanes (Scheme 28) 197). From cis-1,2-dideuteriostyrene, d/-menthyl a-deuteriodiazoacetate and (+)-195d, the cis- and mnw-cyclopropanes 196 were obtained, both with 90% optical purity. The dominant enantiomer of trans-196 had (+)-(15, IS, 35) configuration. Analogously, the cyclopropanes c -198 and trans-198, obtained from styrene, d/-menthyl a-deuteriodiazoacetate and (+)-195d with subsequent transesterification of cisjtrans-197, had optical purities of 86 and 89%, respectively. The major optical isomer of cis-198 had (IS, 2R) configuration, that of trans-198 (IS, 2S) configuration. 

This sequence was obviously not amenable to a synthesis of optically active a-allokainic acid given the fact that an aminomalonate group was necessary. After unfruitful assays with menthyl esters, the Swiss group was rewarded by the discovery that the phenylmenthyl group (180) brings sufficient asymmetry to the reaction intermediate to afford products with a high percentage of favorable diastereoisomer (Scheme 35) (181). 

In 1958 Herbrandson and Cusano (103) prepared menthyl esters of p-iodobenzenesulfinic acid 62. Darwish and McLearen (104) described the synthesis and separation of diastereomeric esters 63 from optically active a-methylbenzyl alchols. Similarly, methane-sulfinyl chloride 64 was found to react with cholesterol to give a... 

In addition to sulfimides, the nitrogen analogs of sulfinates and sulfinamides are chiral and have been obtained as optically active compounds. For instance, the synthesis of diastereomeric menthyl p-toluenesulfinimidoates 90 mentioned above was effected by Cram and his collaborators (18,137) on two ways. The first comprised the reaction of racemic A -tosyl-p-tolueneiminosulfinyl chloride 92 with menthol, followed by separation of the diastereomers of 90, whereas in the second method the reaction of the ester (->45 with chloramine T was utilized. 

Asymmetric synthesis in aldol-type reaction involving magnesium ester or lactone enolates has also been reported. Enolate of (—)-menthyl or (-l-)-bornyl acetate reacts with substituted benzophenones or a-naphtophenones to yield, upon hydrolysis of the resulting esters, optically active /3-hydroxyacids. Although these results are interpreted in terms of a steric factor. Prelog s rules are not applicable to these reactions (equation 88). 

Racemic diphosphines may be resolved by using transition metal complexes that contain optically active olefinic substrates (Scheme 11) (24). When racemic CHIRAPHOS is mixed with an enantiomerically pure Ir(I) complex that has two ( —)-menthyl (Z)-a-(acetam-ido)cinnamate ligands, (S,5)-CHIRAPHOS forms the Ir complex selectively and leaves the R,R enantiomer uncomplexed in solution. Addition of 0.8 equiv of [Rh(norbomadiene)2]BF4 forms a catalyst system for the enantioselective hydrogenation of methyl (Z)-a-(acetamido)cinnamate to produce the S amino ester with 87% ee. Use of the enantiomerically pure CHIRAPHOS-Rh complex produces the hydrogenation product in 90% ee. These data indicate that, in the solution containing both (S,S)-CHIRAPHOS-Ir and (/ ,/ )-CHIRAPHOS-Rh complexes, hydrogenation is catalyzed by the Rh complex only. 

The Rh(II)-catalyzed reaction has been further extended to enantio-selective cyclopropenation of alkynes by diazo esters (Scheme 96) (230). The yield and selectivity are moderate, but optically active cyclopropenes are otherwise very difficult to obtain. An interesting double stereodifferentiation is seen in the reaction of (+)- or (—)-menthyl diazoacetate. 

The most widely investigated optically active poly-acrylic-esters are the polymers of bomyl and menthyl acrylate and methacrylate in this case the monomers have been polymerized by radical polymerization using benzoyl-peroxide (135), A. I. B. N. (134, 135), y-rays (131, 135), U. V. rays (4) in the presence of benzoin (134), and by anionic polymerization using LiC4H9 (4, 135) or C6H5MgBr (134, 135) as catalyst. 

In fact sorbic acid (XXXIII) has been transformed in menthyl-sorbate and the ester (XXXIV) has been polymerized (36) by butyl-lithium (Scheme 6) the prevalence of asymmetric carbon atoms having one of the possible configurations in the main chain of the polysorbic acid (XXXV), not isolated by the authors, has been proved by oxidizing the polymer and measuring the optical activity of the obtained methyl succinic acid, which actually was optically active and had an optical purity of 6% (36). 

In the reaction of the optically active manganese menthyl esters 1 with sodium methoxide in methanol, a transesterification occurs [Eq. (2)]. The menthoxide ion is replaced by the methoxide ion. In the solvent methanol the equilibrium lies completely on the side of the methyl derivatives 2, which can be isolated in high yields7,8. ... 

If the (t)-rotating ester la is used for this sequence of reactions the (+)-rotating salt 3a is produced. In the same way, starting with the (->rotating ester lb the (-)-salt 3b is obtained11. The reactions 3 are best carried out at -20 °C in toluene solution in order to suppress the racemization of the menthyl esters 1. The salts 3 are optically stable in the solid state as well as in solution. As 3a and 3b are also stable to air and heat, they can be stored indefinitely and represent suitable starting materials for the preparation of other optically active compounds, as the following examples show. 

In the reaction of the optically active iron menthyl esters 10 with Li methyl, the esters are converted into the acetyl derivatives 12 and Li menthoxide is eliminated27. If in reaction 9 the (+)-rotating ester 10a is used, the (- rotating acetyl derivative 12b is formed and the (—)-rotating ester 10b affords the (+)-rotating acetyl derivative i2a27. ... 

Poor (<4% de) to modest (56% de) amounts of diastereofacial selection is observed in the cycloaddition of nitrile oxides to optically active acrylates. The plan in each case, of course, was to use a chiral auxiliary which would preferentially shield one of the two ir-faces of the dipolarophile. Of the auxiliaries used, the sulfonamide esters derived from (+)-camphorsulfonyl chloride worked best, the menthyl esters derived from (-)-menthol the poorest (<4% de). As illustrated in Table 19, changes in both temperature and solvent had either no or little affect on the product ratios. Unlike Diels-Alder reactions, the addition of Lewis acids, specifically Et2AlCl, EtAlCh and TiCL, resulted in significant decreases in both the rate of cycloaddition and isolated yield, without an appreciable change in diastereomer ratio. ... 

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