Iridium‐Catalyzed Reductive Strecker Reaction for Late‐Stage Amide and Lactam Cyanation
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- Ángel L. Fuentes de Arriba
- Department of Chemistry Chemistry Research Laboratory University of Oxford 12 Mansfield Road Oxford OX1 3TA UK
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- Elena Lenci
- Department of Chemistry Chemistry Research Laboratory University of Oxford 12 Mansfield Road Oxford OX1 3TA UK
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- Mahendra Sonawane
- Department of Chemistry Chemistry Research Laboratory University of Oxford 12 Mansfield Road Oxford OX1 3TA UK
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- Odilon Formery
- Department of Chemistry Chemistry Research Laboratory University of Oxford 12 Mansfield Road Oxford OX1 3TA UK
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- Darren J. Dixon
- Department of Chemistry Chemistry Research Laboratory University of Oxford 12 Mansfield Road Oxford OX1 3TA UK
抄録
<jats:title>Abstract</jats:title><jats:p>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(C<jats:sub>6</jats:sub>H<jats:sub>5</jats:sub>)<jats:sub>3</jats:sub>]<jats:sub>2</jats:sub> (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.</jats:p>
収録刊行物
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- Angewandte Chemie International Edition
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Angewandte Chemie International Edition 56 (13), 3655-3659, 2017-02-24
Wiley