A Stereoselective Synthesis of the Carbon Backbone of Phoslactomycin B
A convergent synthesis of the entire carbon framework of phoslactomycin B is disclosed. An initial route aimed to create the C-8 tetrasubstituted stereocentre through regioselective intermolecular coupling between an internal alkyne and an allyl silyl ether, adopting Trost's protocol, followed by [2,3] sigmatropic rearrangement. But this was not successful. In a second approach, a propargylic sulfide was rearranged to give an unsaturated ketone. This was then treated with lithio acetonitrile to create the C-8 stereocentre selectively. The C-4 and C-5 stereocentres were introduced by a non-Evans syn-aldol reaction using Crimmins's protocol. The C-9 and C-11 carbinol centres were created by asymmetric transfer hydrogenation. The (Z,Z)-diene moiety was introduced by partial reduction of a diyne following Hansen's modification of the Boland reduction reaction.