Stereochemical investigations in chiral etyhl esters

Abstract

The thesis entitled “Stereochemical Investigations in Chiral Ethyl Esters” attempts to interpret differences in the magnitudes of anisochrony of the O methylene protons of ethyl ester groups located in various chiral environments. In the introductory chapter (Chapter I), because of the requirements of the work described, the background has been treated rather extensively. In Chapter II, the somewhat complex developments leading to the present day understanding of the anisochrony of geminal entities are reviewed, culminating in the recent clarifications provided in a seminal paper by Mislow, Reisse, and their collaborators. Chapter III attempts a creative reinterpretation of the anisochronous behaviour of the O methylene protons of the ethyl ester functions in the triethyl esters of the meso, trans and cis, trans forms of 3,3 dimethylcyclohexane 1,2,3 tricarboxylic acid, which are isolates from the oxidative degradation of diterpene acids. The hitherto undescribed meso, cis form of this acid was obtained by utilising the observations that methylation at C3 of an isomer of trimethyl 1 methylcyclohexane 1,2,3 tricarboxylate, a precursor of the cis, trans form, depends on the time interval allowed to elapse between C3 enolate ion formation and quenching with methyl iodide, and that quenching after a short interval yields the meso, cis form in somewhat higher proportion. The central (C2) ester function of the triethyl ester of this form was found to exhibit anisochrony even though placed in a formally achiral environment. An explanation for this phenomenon, based on atropisomerism of the C2 ester function induced by higher order steric and polar interactions with the flanking (C1 and C3) substituents, is described in Chapter IV. Comparisons among several H and Me substituted cyclic esters revealed that in several cases the O methylated ethyl esters exhibit a lower degree of anisochrony than their unmethylated analogues. In attempting an explanation of this observation-which seemed to be in formal violation of a heuristic developed by Binsch-several possibilities were investigated, and an explanation based on CNDO/2 calculations on methyl isobutyrate and methyl pivalate was arrived at. The explanation utilises the fact that in cases where the larger component of the gradient anisotropy in the neighbourhood of the prochiral protons is parallel to the ester axis, a qualitative judgement that these protons are in very different or very similar environments is possible. A number of examples are given in Chapter V where such a judgement is shown to hold for explaining the observed differences. In attributing atropisomeric stabilisation of a chiral rotamer of the C2 ester function in the meso, cis triethyl ester (Chapter IV), we were aided by an earlier observation that in di t butyl thioacetic esters two rotameric forms are stabilised. In Chapter VI are described the methods adopted to demonstrate whether or not either rotamer had a chiral form. Since anisochrony was not observed, a chiral form was not involved. Here again, CNDO/2 calculations show why only the form in which the thiocarbonyl eclipses the hydrogen and its 180° rotamer (both achiral) are stabilised.