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

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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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