title: Sequential C-Si bond formations from diphenylsilane: application to silanediol peptide isostere precursors.
abstract: The report of silanediol peptide isosteres as highly active inhibitors of proteolytic enzymes has triggered an increased interest for these compounds, thereby necessitating a general and direct synthetic access to this unusual class of protease inhibitors. In this paper, we report on the two-step assembly of the carbon-silicon backbone of a silane-containing dipeptide fragment. The synthetic scheme is comprised of an alkene hydrosilylation step with the simple precursor, diphenylsilane, using either a radical initiator or RhCl(PPh3)3, Wilkinson's catalyst, for the creation of a hydridosilane and the first new carbon-silicon bond. The next step is the reduction of this hydridosilane with lithium metal providing a silyl lithium reagent, which undergoes a highly diastereoselective addition to an optically active tert-butanesulfinimine, thus generating the second C-Si bond. This method allows sequential functionalization of the two hydrides in diphenylsilane by chemoselective discrimination.
authors.affiliation: Center for Insoluble Protein Structures, Department of Chemistry, and Interdisciplinary Nanoscience Center, University of Aarhus, Langelandsgade 140, 8000 Aarhus C, Denmark.
authors.forename: Lone
authors.initials: L
authors.lastname: Nielsen
authors.forename: Troels
authors.initials: T
authors.lastname: Skrydstrup