Sequential C-Si Bond Formations from Diphenylsilane: Application to Silanediol Peptide Isostere Precursors

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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.
Original languageEnglish
JournalJournal of the American Chemical Society
Volume130
Issue39
Pages (from-to)13145–13151
Number of pages7
ISSN0002-7863
Publication statusPublished - 2008

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