Reductive carbocyclization of homoallylic alcohols by a boron-catalyzed dual ring-closing pathway

Abstract

Cyclobutanes and their derivatives are frequent scaffolds that are found in various bioactive products. Herein we report the first case of the transition-metal free reductive cyclization reaction of homoallylic alcohols to cyclobutanes using tris(pentafluorophenyl)borane catalyst. Reduced cyclobutanes showed a broad range of scope, to provide 1,2-disubstituted arylcyclobutanes under ambient conditions. With stoichiometric amount of hydrosilane reducing agents, the catalysis proceeds cis-selectively. The electronic and steric variations in the C-3 carbon that is with aryl group substituents slightly influenced the substrate reactivity. Deuterium-labelling, comparative experiments, and initial rate measurements for KIE, Hammett study and DFT calculations allowed to differentiate the most appropriate reaction mechanism. The precise and detailed mechanism revealed that (i) the release of disiloxane that is coupled to the intramolecular cyclization is rate-determining, (ii) both four- and three-membered carbocation species could be formed during the ring-closing step, and (iii) the cationic cyclopropyl intermediate can be expanded easily and selectively reduced to syn-cyclobutanes, especially without electron donating groups at C-4 position.