Asymmetric three-component olefin dicarbofunctionalization enabled by photoredox and copper dual catalysis.

Peng-Zi Wang,Yuan Gao,Jun Chen,Xiao-Die Huan,Jia-Rong Chen,Wen-Jing Xiao

doi:10.1038/s41467-021-22127-x

Peng-Zi Wang, Yuan Gao + Show 4 more

Open Access

https://doi.org/10.1038/s41467-021-22127-x

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Abstract

The intermolecular three-component alkene vicinal dicarbofunctionalization (DCF) reaction allows installation of two different carbon fragments. Despite extensive investigation into its ionic chemistry, the enantioseletive radical-mediated versions of DCF reactions remain largely unexplored. Herein, we report an intermolecular, enantioselective three-component radical vicinal dicarbofunctionalization reaction of olefins enabled by merger of radical addition and cross-coupling using photoredox and copper dual catalysis. Key to the success of this protocol relies on chemoselective addition of acyl and cyanoalkyl radicals, generated in situ from the redox-active oxime esters by a photocatalytic N-centered iminyl radical-triggered C-C bond cleavage event, onto the alkenes to form new carbon radicals. Single electron metalation of such newly formed carbon radicals to TMSCN-derived L1Cu(II)(CN)2 complex leads to asymmetric cross-coupling. This three-component process proceeds under mild conditions, and tolerates a diverse range of functionalities and synthetic handles, leading to valuable optically active β–cyano ketones and alkyldinitriles, respectively, in a highly enantioselective manner (>60 examples, up to 97% ee).

Highlights

The intermolecular three-component alkene vicinal dicarbofunctionalization (DCF) reaction allows installation of two different carbon fragments
In addition to 6aa, a significant amount of side products sp-1, sp-2, and sp-3 were detected, which might result from acyl radical 3a-II-mediated two-component cross-coupling with 1a and TMSCN, or its own dimerization
Key to the success of this protocol relies on chemoselective addition of acyl and cyanoalkyl radicals, generated in situ from the redox-active oxime esters by a photocatalytic N-centered iminyl radical-triggered C–C bond cleavage event, onto the alkenes to form new carbon radicals

Summary

Introduction

The intermolecular three-component alkene vicinal dicarbofunctionalization (DCF) reaction allows installation of two different carbon fragments. Single electron metalation of such newly formed carbon radicals to TMSCN-derived L1Cu(II)(CN)[2] complex leads to asymmetric cross-coupling This three-component process proceeds under mild conditions, and tolerates a diverse range of functionalities and synthetic handles, leading to valuable optically active β–cyano ketones and alkyldinitriles, respectively, in a highly enantioselective manner (>60 examples, up to 97% ee). Visible-light photoredox catalysis has emerged as a powerful tool for organic chemists to develop many elusive radical-mediated chemical transformations with high levels of functional group tolerance[34,35,36,37] This activation mode provides a promising approach for the development of radical multicomponent reactions (in some cases with excellent stereoselectivity)[38,39,40,41,42,43]. This protocol would provide an efficient and general approach for preparation of valuable optically active β-cyano ketones and alkyldinitriles[61,62,63]

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