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Synthesis of Hypervalent Iodonium Alkynyl Triflates for the Application of Generating Cyanocarbenes
Published on: September 8, 2013
Iridium-Catalyzed Reductive Strecker Reaction for Late-Stage Amide and Lactam Cyanation
Ángel L Fuentes de Arriba1, Elena Lenci1, Mahendra Sonawane1
1Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
Abstract:
A new iridium-catalyzed reductive Strecker reaction for the direct and efficient formation of α-amino nitrile products from a broad range of (hetero)aromatic and aliphatic tertiary amides, and N-alkyl lactams is reported. The protocol exploits the mild and highly chemoselective reduction of the amide and lactam functionalities using IrCl(CO)[P(C6 H5 )3 ]2 (Vaska's complex) in the presence of tetramethyldisiloxane, as a reductant, to directly generate hemiaminal species able to undergo substitution by cyanide upon treatment with TMSCN (TMS=trimethylsilyl). The protocol is simple to perform, broad in scope, efficient (up to 99 % yield), and has been successfully applied to the late-stage functionalization of amide- and lactam-containing drugs, and naturally occurring alkaloids, as well as for the selective cyanation of the carbonyl carbon atom linked to the N atom of proline residues within di- and tripeptides.
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