The strain limit in intramolecular nucleophilic substitution

Abstract

Kinetics and products of reactions of sulfonyl-stabilised carbanions bearing ω-leaving groups have been examined. The intention was to explore the upper limit of strain that can be tolerated for intramolecular nucleophilic substitution in these systems and the effect on enthalpy of activation for carbocycle formation.

In protic solvents, the upper limit of excess enthalpy differential (EED) between starting compound and product is ca. 160 kJ mol^–1. Above this limit, competing reactions, usually unactivated 1,2-elimination, supervene. As found in earlier work with less strained substrates, cyclisation to give three-membered rings is much faster than for four-membered rings.

In aprotic solvents in which substrates can be completely deprotonated, cyclisation to give very strained products can readily be achieved.