Total Synthesis of (−)-Virginiamycin M₂: Application of Crotylsilanes Accessed by Enantioselective Rh(II) or Cu(I) Promoted Carbenoid Si–H Insertion

Citations Over TimeTop 14% of 2011 papers

Abstract

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.

Related Papers

• → Convenient Preparation of Indolyl Malonates via Carbenoid Insertion(2002)91 cited
• → The first example of magnesium carbenoid 1,3-CH insertion reaction: a novel method for synthesis of cyclopropanes from 1-chloroalkyl phenyl sulfoxides in high yields(2004)28 cited
• → An enantiospecific synthesis of (−)-2-pupukeanone via a rhodium carbenoid CH insertion reaction(2001)18 cited
• → Intermolecular C-H and Si-H Insertion Reactions with Halodiazoacetates(2008)11 cited
• → Synthesis of spirosystems by rhodium(II)-carbenoid CH insertion reactions(1998)15 cited