α-Branched amines through radical coupling with 2-azaallyl anions, redox active esters and alkenes.

Shengzu Duan,Jielun Cong,Patrick J Walsh,Xiaodong Yang,Yujin Zi,Minyan Li,Lingling Wang,Wen Chen,Hongbin Zhang

doi:10.1039/d2sc00500j

Shengzu Duan, Jielun Cong + Show 7 more

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https://doi.org/10.1039/d2sc00500j

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Journal: Chemical science	Publication Date: Jan 1, 2022
Citations: 5	License type: CC BY 3.0

Affiliation: Yunnan University, University of Pennsylvania

Abstract

α-Branched amines are fundamental building blocks in a variety of natural products and pharmaceuticals. Herein is reported a unique cascade reaction that enables the preparation of α-branched amines bearing aryl or alkyl groups at the β- or γ-positions. The cascade is initiated by reduction of redox active esters to alkyl radicals. The resulting alkyl radicals are trapped by styrene derivatives, leading to benzylic radicals. The persistent 2-azaallyl radicals and benzylic radicals are proposed to undergo a radical–radical coupling leading to functionalized amine products. Evidence is provided that the role of the nickel catalyst is to promote formation of the alkyl radical from the redox active ester and not promote the C–C bond formation. The synthetic method introduced herein tolerates a variety of imines and redox active esters, allowing for efficient construction of amine building blocks.

Highlights

Amines with a-branching are important functional groups in bioactive compounds,[1] natural products,[2,3] and medications.[4]
Inspired by the single electron transfer (SET) behavior of 2azaallyl anions, we examined the applications of 2-azaallyl anions in the synthesis of amines
The emergence of redox active esters (RAEs) as alkyl radical precursors has marked a milestone in the art of organic synthesis (Scheme 3a),[49–60] when combined with transition metal-catalyzed processes, such as alkene

Summary

Introduction

Amines with a-branching are important functional groups in bioactive compounds,[1] natural products,[2,3] and medications.[4]. The persistent 2-azaallyl radicals and benzylic radicals are proposed to undergo a radical– radical coupling leading to functionalized amine products. A more atom economical method employs transition-metal-catalyzed C–H bond activation followed by addition of the resulting organometallic nucleophile to imines (Scheme 1b).[11–13] The a-functionalization of amines toward the formation of a-branched derivatives has been developed.

Results

Conclusion