Construction of axial chirality via asymmetric radical trapping by cobalt under visible light

Abstract

3d-Metals have been identified as economic and sustainable alternatives to palladium, the frequently used metal in transition-metal-catalyzed cross-couplings. However, cobalt has long stood behind its neighboring elements, nickel and copper, in asymmetric radical couplings, owing to its high catalytic activity in the absence of ligands. Here, we disclose an asymmetric metallaphotoredox catalysis (AMPC) strategy for the dynamic kinetic resolution (DKR) of racemic heterobiaryls, which represents the first example of visible-light-induced, asymmetric radical couplings for the construction of axial chirality. This success can also be extended to the reductive cross-coupling variant featuring on more easily available feedstocks. The keys to these successes are the rational design of a sustainable AMPC system by merging asymmetric cobalt catalysis with organic photoredox catalysis and, perhaps more importantly, the identification of an efficient chiral polydentate ligand.

Photoinduced Cobalt-Catalyzed Desymmetrization of Dialdehydes to Access Axial Chirality

“…(3) competitive processes, such as hydrogenation of aryl iodides. Based on our continuous interest in asymmetric photochemical synthesis, 10,11,16 we developed the photoinduced cobalt-catalyzed desymmetrizing reductive coupling of axially prochiral dialdehydes 17 and aryl iodides or alkynes to access axially chiral aldehydes.…”

“…Recently, our group reported a visible light-induced Minisci reaction catalyzed by chiral phosphoric acid to produce axially and centrally chiral heterobiaryls . We also developed a metallaphotoredox catalysis strategy for the dynamic kinetic asymmetric transformation of racemic heterobiaryls, which underwent photoredox radical coupling for the construction of axially chiral heterobiaryls . Despite these significant advances in light-driven processes, exploring novel catalytic enantioselective strategies and multiple catalysis systems to construct optically active axially chiral compounds is essential.…”

“…10 We also developed a metallaphotoredox catalysis strategy for the dynamic kinetic asymmetric transformation of racemic heterobiaryls, which underwent photoredox radical coupling for the construction of axially chiral heterobiaryls. 11 Despite these significant advances in light-driven processes, exploring novel catalytic enantioselective strategies and multiple catalysis systems to construct optically active axially chiral compounds is essential. Inspired by the pioneering research reported by the Xia et al 12 and our recent work 13 on dual photoredox/cobalt catalysis, 14,15 we speculated whether the asymmetric photoinduced cobaltcatalyzed reductive coupling combined with the desymmetrization strategy could be applied to the synthesis of centrally and axially chiral biaryls (Figure 1c).…”

“…The potential challenges for this strategy include: (1) simultaneous stereocontrol of central and axial chirality, (2) recognition of symmetrical aldehyde groups of biaryls and avoiding over-reduction, and (3) competitive processes, such as hydrogenation of aryl iodides. Based on our continuous interest in asymmetric photochemical synthesis, ,, we developed the photoinduced cobalt-catalyzed desymmetrizing reductive coupling of axially prochiral dialdehydes and aryl iodides or alkynes to access axially chiral aldehydes.…”

Dynamic Kinetic Reductive Conjugate Addition for Construction of Axial Chirality Enabled by Synergistic Photoredox/Cobalt Catalysis

“…However, Earth-abundant metal-catalyzed DYKAT chemistry involving heterobiaryls has not been well exploited owing to a lack of efficient catalytic systems. Recently, our group realized a photomediated cobalt-catalyzed asymmetric radical coupling reaction involving a DYKAT, with the combination of an octahedral cobalt coordination catalyst and a chiral sulfanilamide bisphosphine ligand, the key to achieving enantioselectivity. Inspired by this work and our interest in asymmetric photocatalysis , and cobalt catalysis, we envisaged the use of cobalt-catalyzed DYKATs to asymmetrically add heterobiaryl triflates to conjugated alkenes promoted by visible light, a plausible reaction mechanism for which is shown in Figure c.…”