Investigations in terpenes : studies in the stereochemistry of polysubstituted cyclohexane derivatives

Abstract

This thesis, entitled “Investigations in Terpenes: Studies in the Stereochemistry of Polysubstituted Cyclohexane Derivatives,” is divided into three Parts.

Part I Part I is divided into three chapters. Chapter I gives a comprehensive review of the role of 1,3?dimethylcyclohexane?1,2,3?tricarboxylic acid (the C??acid) (I) and its homologue, 1,3?dimethyl?1,3?dicarboxy?cyclohexyl?2?acetic acid (the C???acid) (II), in the elucidation of the structures and stereochemical relationships in abietic acid and related diterpene acids. Chapter II discusses the possible configurations and conformations of three of the four possible stereoisomers of trimethyl 1?methylcyclohexane?1,2,3?tricarboxylates (III), which are the precursors in the syntheses of the cis, trans (dl) and the trans, meso C??acids (I). This discussion is based on a study of the nuclear magnetic resonance (NMR) spectra of these triesters as well as those of the related compounds:

ethyl 1?methyl?2,3?dicyanocyclohexane?1?carboxylate (IV), and dimethyl 1?methyl?3?cyanocyclohexane?1,2?dicarboxylate (V).

Relevant chemical evidence is also presented in support of the conformational assignments. Chapter III describes attempts to methylate the isomers of the dicyano?esters (IV) and cyano?diesters (V), which resulted in elimination of the C??cyano function in (IV) and the C??cyano function in (V). None of the expected methylation products could be isolated. A review of the carbanion (E1cB) elimination mechanism is also given in relation to these elimination reactions.

Part II In Part II, three methods of preparation of the previously undescribed cyclohexane?1,2,3?tricarboxylic acid (VI) are presented. Each method, differing in stereoselectivity, led to strikingly different isomer compositions. All three possible stereoisomers were synthesised, and their stereochemistry was elucidated based on both chemical and physical evidence.

Part III Part III begins with a brief review of the A1,3_{1,3}1,3? interaction. The stereoselectivity observed in the addition of hydrogen chloride to cyclohex?1?enecarbonitrile (VII) in alcoholic and other media has been explained on the basis of a possible interaction between the lone pairs on chlorine and the C?N ??orbital in the postulated intermediate 2?chlorocyclohexylidenemethylideneimine (VIII). In this thesis, an attempt has been made to evaluate the importance of two types of strain, namely:

A1,3_{1,3}1,3? strain (axial?axial), and A1,2_{1,2}1,2? strain (vicinal axial?equatorial),

in allylic systems, and their role in enolate ion formation, the stability of intermediates, and also in determining the stereochemistry of products formed during:

hydrogenation (A1,2_{1,2}1,2? interaction), and sodium borohydride reduction (A1,3_{1,3}1,3? interaction).

The texts of three published papers have been appended to this thesis.