Nickel-Catalyzed Cross-Coupling of Photoredox-Generated Radicals: Uncovering a General Manifold for Stereoconvergence in Nickel-Catalyzed Cross-Couplings

Abstract

The cross-coupling of sp3-hybridized organoboron reagents via photoredox/nickel dual catalysis represents a new paradigm of reactivity for engaging alkylmetallic reagents in transition-metal-catalyzed processes. Reported here is an investigation into the mechanistic details of this important transformation using density functional theory. Calculations bring to light a new reaction pathway involving an alkylnickel(I) complex generated by addition of an alkyl radical to Ni(0) that is likely to operate simultaneously with the previously proposed mechanism. Analysis of the enantioselective variant of the transformation reveals an unexpected manifold for stereoinduction involving dynamic kinetic resolution (DKR) of a Ni(III) intermediate wherein the stereodetermining step is reductive elimination. Furthermore, calculations suggest that the DKR-based stereoinduction manifold may be responsible for stereoselectivity observed in numerous other stereoconvergent Ni-catalyzed cross-couplings and reductive couplings.

Visible‐Light Photocatalysis as an Enabling Tool for the Functionalization of Unactivated C(sp3)‐Substrates

“…[60] The mechanism was investigated by DFT calculations, which supported both (i) addition of the alkyl radical to , followed by oxidative addition of the aryl bromide (Scheme 23B), and (ii) an alternative pathway, oxidative addition followed by radical addition to an Ni II complex (Scheme 7D). [61] Both pathways converged to a pentacoordinate Ni III complex, which gave the final product after reductive elimination. Alkyltrifluoroborates have also been used as substrates in cyanation reactions and can be oxidatively activated either by an Ru photocatalyst or by an organic-dye-based photocatalyst.…”

Photoredox Catalysis in Nickel-Catalyzed Cross-Coupling

“…The seminal breakthrough in cross-coupling of secondary alkyltrifluoroborates came with the development of an elegant and mild protocol combining visible light photoredox/nickel dual catalysis to allow cross-couplings reactions of these nucleophiles [17]. This approach takes advantage of the fact that the effective transmetalation step, in which the alkyl group on boron ends up on the nickel center through a net one-electron oxidation of the Ni (Scheme 2), is a virtually barrierless process [9]. This single electron pathway thus transforms the problematic, highenergy, two-electron transmetalation into a facile one-electron process.…”

“…Once this unique paradigm of reactivity was established, a computational analysis of the process was conducted to gain insight into and confirm the intricacies of this novel class of reaction [9]. As outlined previously (Scheme 2), these studies revealed that the radical formed in the photoredox cycle can add to nickel either after or before oxidative addition, depending on the concentration of Ni(0) or Ni(II), with both pathways converging to a common Ni(III) intermediate.…”

“…A prototypical mechanistic scenario for photoredox/Ni dual catalytic crosscoupling is depicted in Scheme 2 [9]. In the photoredox cycle, a C(sp3)-hybridized radical is generated from SET oxidation of a suitable precursor by an excited-state photocatalyst (PC) complex.…”

Protecting group-free, selective cross-coupling of alkyltrifluoroborates with borylated aryl bromides via photoredox/nickel dual catalysis

“…This strategy would be enabled by our recently developed single-electron transmetalation manifold, wherein sp 3 -hybridized organoboron reagents participate in Ni-catalyzed cross-coupling through oxidative fragmentation to an alkyl radical promoted by an Ir photoredox catalyst (22)(23)(24). Our previous observation (22) that an sp 3 -hybridized organotrifluoroborate participates in photoredox/nickel dualcatalytic cross-coupling selectively in the presence of an sp 2 -hybridized organotrifluoroborate confirmed that the single-electron transmetalation activation mode is, indeed, orthogonal to the traditional two-electron regime under relevant reaction conditions.…”