Catalytic Enantioselective Dihalogenation and the Selective Synthesis of (-)-Deschloromytilipin A and (-)-Danicalipin A.

ABSTRACT

A titanium-based catalytic enantioselective dichlorination of simple allylic alcohols is described. This dichlorination reaction provides stereoselective access to all common dichloroalcohol building blocks used in syntheses of chlorosulfolipid natural products. An enantioselective synthesis of ent-(-)-deschloromytilipin A and a concise, eight-step synthesis of ent-(-)-danicalipin A are executed and employ the dichlorination reaction as the first step. Extension of this system to enantioselective dibromination and its use in the synthesis of pentabromide stereoarrays relevant to bromosulfolipids is reported. The described dichlorination and dibromination reactions are capable of exerting diastereocontrol in complex settings allowing X-ray crystal structure analysis of natural and unnatural diastereomers of polyhalogenated stereohexads.