The Surprising Reactivity of Chloromethyl Chlorosulfate with Active Methylene Compounds

Abstract

Condensation of chloromethyl chlorosulfate (1) with alkyl 1,3‐keto esters under phase‐transfer catalysis (PTC) conditions led to methylene bridged bis‐acetoacetates through a sequential chloromethylation‐β‐elimination‐Michael addition process. The latter compounds further evolved towards polyfunctional dihydrofuran and tetrahydropyran derivatives by competitive chloromethylation/chlorination reaction. In aprotic organic solvent, chlorination of the methylene active group is the main process and proceeded by reaction of the enolate of acetoacetate with the chlorine atom bound to the sulfonyl group of 1. The reactivity of some other active methylene compounds under PTC conditions was investigated. Acetylacetone reacted similarly to ethyl acetoacetate providing O‐heterocycles while ethyl cyanoacetate gave diethyl 2,4‐dicyanoglutaric acid diethyl ester together with 2‐diethyl 1,2‐dicyanocyclopropane‐1,2‐dicarboxylate. A plausible reaction mechanism is proposed whose the key feature is the competitive halogenation/chloromethylation of the intermediate methylene bridge dimeric active methylene compounds followed by intramolecular cyclization.