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Transition‐Metal‐Free Reductive Functionalization of Tertiary Carboxamides and Lactams for α‐Branched Amine Synthesis
Author(s) -
Ong Derek Yiren,
Fan Dongyang,
Dixon Darren J.,
Chiba Shunsuke
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202004272
Subject(s) - chemistry , reagent , surface modification , combinatorial chemistry , cyanide , hemiaminal , transition metal , sodium iodide , nucleophilic substitution , sodium cyanide , organic chemistry , catalysis
A new method for the synthesis of α‐branched amines by reductive functionalization of tertiary carboxamides and lactams is described. The process relies on the efficient and controlled reduction of tertiary amides by a sodium hydride/sodium iodide composite, in situ treatment of the resulting anionic hemiaminal with trimethylsilyl chloride and subsequent coupling with nucleophilic reagents including Grignard reagents and tetrabutylammonium cyanide. The new method exhibits broad functional‐group compatibility, operates under transition‐metal‐free reaction conditions, and is suitable for various synthetic applications on both sub‐millimole and on multigram scales.