Studies in the stereochemistry of alkylation importance of gegenion co-ordination

Abstract

This thesis describes investigations into the effects of methyl and ester functions as substituents syn-axial to the ?-centre in 6-cyclic carboxylic esters when ?-enolate formation is attempted. The effects manifest themselves as: (1) The inability of the ?-hydrogen, presumed to be axial, to undergo ionisation in case the syn-axial substituent is methyl. (2) Tight ion-pairing in case the syn-axial substituent is an ester function. (3) A commanding degree of stereoselectivity exerted by the coordinated gegenion. The background information regarding the assignment of conformations, based on NMR spectroscopic evidence, to the three “C-10 triesters” of which two (designated A and B) were stated to undergo regioselective and highly stereoselective methylation and the third (C), not to undergo methylation under the same conditions, are critically reviewed. In the next part, the literature on gegenion coordination is selectively reviewed. The evidence for the aggregate nature of ion-pair agglomerates in certain media, the loosening of ion-pairs by “effective additives” and the nature of the action of crown ethers has been highlighted. The synthesis of methyl 9-ethoxycarbonyl-trans-decalin-2-carboxylate I and methyl 9-methyl-trans-decalin-2-carboxylate II, conformational models of the C-10 triesters A (or B) and C respectively, and a study of their behaviour under enolising and methylating conditions are presented. Both I and II fail to undergo methylation for the reasons that the anion is not formed from II and the alkylating agent fails to displace the gegenion tightly paired by the anion from I. In order to ensure that the reaction conditions were well-controlled for drawing conclusions from the negative results with I, in which a role for the gegenion is implied, the results of alkylations of related systems, under the conditions adopted throughout (Ph?CNa – Ether – CH?I), are described. The successful methylation of the enolate of I after the removal of tight pairing by Li-HMPA, capable of stronger coordination with the gegenion, and the reinvestigation of the methylation of the C-10 triesters are discussed in the final sections which are then followed by description of the experiments.