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

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.