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. 2021 May 10;60(20):11227-11230.
doi: 10.1002/anie.202101782. Epub 2021 Apr 8.

Palladium-Mediated Cγ -H Functionalization of Alicyclic Amines

Ellen Y Aguilera  1 , Melanie S Sanford  1
Affiliations

Palladium-Mediated Cγ -H Functionalization of Alicyclic Amines

Ellen Y Aguilera et al. Angew Chem Int Ed Engl. .

Abstract

This paper describes a new method for the transannular functionalization of the γ-C-H bonds in alicyclic amines to install C(sp3 )-halogen, oxygen, nitrogen, boron, and sulfur bonds. The key challenge for this transformation is controlling the relative rate of Cγ -H versus Cα -H functionalization. We demonstrate that this selectivity can be achieved by pre-complexation of the substrate with Pd prior to the addition of oxidant. This approach enables the use of diverse oxidants that ultimately install various heteroatom functional groups at the γ-position with high site- and diastereoselectivity.

Keywords: C−H activation; alicyclic amines; palladium; relative rates.

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Figures

Scheme 1.
Scheme 1.
(a) Competing Cα–H versus Cγ–H (b) Our strategy.
Scheme 2.
Scheme 2.
Pd-catalyzed C–H bromination with NBS.
Scheme 3.
Scheme 3.
(a) γ-Br with complex 2-A (b) In situ method for γ-Br. (c) Proposed pathway.
Scheme 4.
Scheme 4.
γ-functionalizations with in situ method.
Scheme 5.
Scheme 5.
Scope of Cγ–BPin functionalization.
See this image and copyright information in PMC

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