title: Iridium-Catalyzed Reductive Strecker Reaction for Late-Stage Amide and Lactam Cyanation.
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(C6H5)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.
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
authors.forename: Ángel L
authors.initials: ÁL
authors.lastname: Fuentes de Arriba
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Lenci
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Sonawane
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
authors.forename: Odilon
authors.initials: O
authors.lastname: Formery
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
authors.forename: Darren J
authors.identifier: 0000-0003-2456-5236
authors.initials: DJ
authors.lastname: Dixon
keywords: cyanide; iridium; nitriles; peptides; reduction; synthetic methods