Total synthesis of (-)-virginiamycin m_2: Application of crotylsilanes accessed by enantioselective Rh(II) or Cu(I) promoted carbenoid Si-H insertion

摘要

A stereoselective synthesis of the antibiotic (-)-virginiamycin M _2 is detailed. A convergent strategy was utilized that proceeded in 10 steps (longest linear sequence) from enantioenriched silane (S)-15. This reagent, which was prepared via a Rh(II)- or Cu(I)-catalyzed carbenoid Si-H insertion, was used to introduce the desired olefin geometry and stereocenters of the C1-C5 propionate subunit. A modified Negishi cross-coupling or an efficient alkoxide-directed titanium-mediated alkyne-alkyne reductive coupling strategy was utilized to assemble the trisubstituted (E,-E)-diene. An underutilized late-stage SmI_2-mediated macrocyclization was employed to construct the 23-membered macrocycle scaffold of the natural product (Figure presented).