Synlett 2021; 32(10): 955-961
DOI: 10.1055/a-1353-7605
synpacts

Asymmetric Synthesis of α-Alkylated γ-Lactam via Nickel/8-Quinim-Catalyzed Reductive Alkyl-Carbamoylation of Unactivated Alkene

Xianqing Wu
,
Mohini Shrestha
,
Yifeng Chen
This work was supported by NSFC/China (21702060), Shanghai Rising-Star Program, Shanghai Municipal Science and Technology Major Project Grant No.2018SHZDZX03) and the Program of Introducing Talents of Discscipline to Universities (B16017), and the Fundamental Research Funds for the Central Universities.


Abstract

Chiral-auxiliary-mediated synthesis represents the most frequently used synthetic tool for the induction of chirality on α-position of γ-lactams in organic synthesis. However, the general strategy requires the stoichiometric use of chiral reagents with multiple manipulation steps. Transition-metal-catalyzed asymmetric alkene dicarbofunctionalization using readily available substrates under mild conditions allows the simultaneous construction of two vicinal chemical bonds and a chiral carbon center, hence, gain expedient access to chiral heterocycles. Herein, we disclose a Ni-catalyzed enantioselective reaction of 3-butenyl carbamoyl chloride and primary alkyl iodide enabled by a newly designed chiral 8-quinoline imidazoline ligand (8-Quinim). This protocol features broad functional group tolerance and high enantioselectivities, achieving unprecedented synthesis of chiral nonaromatic heterocycles via catalytic reductive protocol.

1 Introduction

2 Development of 8-Quinim Ligand

3 Nickel/8-Quinim-Catalyzed Enantioselective Synthesis of Chiral α-Alkylated γ-Lactam

4 Conclusion and Outlook



Publication History

Received: 05 January 2021

Accepted after revision: 14 January 2021

Accepted Manuscript online:
14 January 2021

Article published online:
03 February 2021

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