1 Interdisciplinary Nanoscience Center, Faculty of Science, Aarhus University, Aarhus University2 Department of Chemistry, Faculty of Science, Aarhus University, Aarhus University3 Department of Chemistry - Center for Uopløselige Proteinstrukturer, Department of Chemistry, Science and Technology, Aarhus University4 iNano-School, Science and Technology, Aarhus University5 Department of Chemistry, Science and Technology, Aarhus University6 iNano-School, Science and Technology, Aarhus University7 Department of Chemistry, Science and Technology, Aarhus University
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.
American Chemical Society. Journal, 2008, Vol 130, Issue 39