Reaction of a highly spiro-activated electrophilic cyclopropane with pyridines. The substituent effect on the reaction rate

Abstract

The kinetics of the reactions of 3,3,10,10-tetramethyldispiro[5.0.5.1]trideca-1,5,8,12-tetraone (7) with a series of substituted pyridines were investigated. The compound underwent well behaved second-order reactions with nucleophiles to afford the polar zwitterionic products (9). Values of log k in acetonitrile fall on a straight line when plotted against the pK_a values of a series of 3- or 4-substituted pyridines and exhibit a Brønsted slope of 0.24. Methyl substitution in the neighbourhood of the reaction centre in the substrate or a nucleophile produced a fall in reactivity to some degree (1/2–1/10). These results together with an unusual solvent effect are interpreted by a preassociative mechanism in which a polar encounter complex is formed prior to the cyclopropane ring opening to give the final product (9).