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Iridium‐Catalyzed Reductive Strecker Reaction for Late‐Stage Amide and Lactam Cyanation
Author(s) -
Fuentes de Arriba Ángel L.,
Lenci Elena,
Sonawane Mahendra,
Formery Odilon,
Dixon Darren J.
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201612367
Subject(s) - chemistry , cyanation , amide , trimethylsilyl cyanide , nitrile , strecker amino acid synthesis , combinatorial chemistry , catalysis , iridium , reductive amination , organic chemistry , benzoxazole , medicinal chemistry , enantioselective synthesis
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 6 H 5 ) 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.