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. 2022 Sep 9;24(35):6364-6368.
doi: 10.1021/acs.orglett.2c02148. Epub 2022 Aug 29.

Regioselective α-Cyanation of Unprotected Alicyclic Amines

Fuchao Yu  1   2 , Daniel A Valles  1 , Weijie Chen  1 , Scott D Daniel  1 , Ion Ghiviriga  3 , Daniel Seidel  1
Affiliations

Regioselective α-Cyanation of Unprotected Alicyclic Amines

Fuchao Yu et al. Org Lett. .

Abstract

Secondary alicyclic amines are converted to α-aminonitriles via addition of TMSCN to their corresponding imines, intermediates that are produced in situ via the oxidation of amine-derived lithium amides with simple ketone oxidants. Amines with an existing α-substituent undergo regioselective α'-cyanation even if the C-H bonds at that site are less activated. Amine α-arylation can be combined with α'-cyanation to generate difunctionalized products in a single operation.

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Figures

Scheme 1.
Scheme 1.. Overview of methods for amine α-cyanation
Scheme 2.
Scheme 2.. Scope of the reaction.a
a Unless indicated otherwise, reactions were performed with 0.5 mmol of the amine. Yields correspond to isolated yields of chromatographically purified product. b Reactions were performed with 1 mmol of the amine. c Benzophenone was used as the oxidant. d Yield in parentheses corresponds to a reaction performed on a 15 mmol (2.64 g) scale. e t-Butyl phenyl ketone was used as the oxidant.
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