Enantioselective Cyanofunctionalization of Aromatic Alkenes via Radical Anions

Abstract

Alkene radical ions constitute an integral and unique class of reactive intermediates for the synthesis of valuable compounds because they have both unpaired spins and charge. However, relatively few synthetic applications of alkene radical anions have emerged due to a dearth of generally applicable and mild radical anion generation approaches. Precise control over the chemo-and stereoselectivity in alkene radical anion-mediated processes represents another long-standing challenge due to their high reactivity. To overcome these issues, here, we develop a new redox-neutral strategy that seamlessly merges photoredox and copper catalysis to enable the controlled generation of alkene radical anions and their orthogonal enantioselective cyanofunctionalization via distonic-like species. This new strategy enables highly regio-, chemo-, and enantioselective hydrocyanation, deuterocyanation, and cyanocarboxylation of alkenes without stoichiometric reductants or oxidants under visible light irradiation. This protocol provides a new blueprint for the exploration of the transformation potential of alkene radical anions.

Visible-light-induced Markovnikov addition of olefin for construction of deuterated α-tertiary amino acid derivatives

“…Based on the above experimental results and previous reports, 48–53 the proposed mechanism was depicted in Scheme 2G. Initially, the oxazolone generates the enolate intermediate I in the presence of a solvent or base, followed by the formation of the excited state II* under light irradiation.…”

“…Despite the established utility of alkene radical cations, exploration of alkene radical anions in organic synthesis has been limited due to the lack of widely applicable and mild methods for the controlled single-electron transfer (SET)-based reduction of alkenes. 51 We hypothesized that the photoactive oxazolone intermediate with high reduction potential could function as an electron donor, reducing the alkenes to form alkene radical anions through a SET process, thereby initiating subsequent radical cross-coupling reactions. Herein, we report an efficient redox-neutral strategy for the photochemical Markovnikov addition of alkenes via controlled generation of alkene radical anions (Scheme 1c).…”

Photocatalytic Reductive Functionalization of Aryl Alkynes via Alkyne Radical Anions

“…Possessing both a charge and an unpaired electron, these radical ions can engage in reactions characteristic of both ions and neutral free radicals, thereby facilitating multiple bond formations through unique reaction pathways and modes . While alkene radical cations and anions generated from alkene feedstocks have emerged as a powerful platform in organic synthesis, the analogous utilization of alkyne radical ions, especially for the alkyne radical anions, is rarely studied (Figure a) . This is primarily attributed to the high instability and restricted accessibility of alkyne radical anions, in contrast to the extensively studied alkene radical anions .…”

Enantioselective Synthesis of Axially and Centrally Chiral Styrenes via Nickel-Catalyzed Desymmetric Hydrocyanation of Biaryl Dienes

“…The catalytic asymmetric alkene hydrofunctionalization reaction is one of the most fundamental and effective synthetic methodologies to access central chirality . However, the generation of axially and centrally chiral chemicals via this catalytic asymmetric transformation remains underdeveloped (Scheme C, top).…”