A Cobalt-Catalyzed Enantioconvergent Radical Negishi C(sp³)–C(sp²) Cross-Coupling with Chiral Multidentate N,N,P-Ligand

Abstract

A cobalt-catalyzed enantioconvergent radical Negishi C(sp 3 )−C(sp 2 ) cross-coupling of racemic benzyl chlorides with arylzinc reagents has been developed in good yield with moderate enantioselectivities. This strategy provides an expedient access toward a range of enantioenriched 1,1-diarylmethanes. Key to this discovery is the utilization of a chiral multidentate anionic N,N,Pligand to strongly coordinate with the cobalt catalyst and tune its chiral environment, thus achieving the enantiocontrol over the highly reactive prochiral alkyl radical species.

Cu-Catalyzed Site-Selective Benzylic Chlorination Enabling Net C–H Coupling with Oxidatively Sensitive Nucleophiles

“…Benzylic chlorides are versatile synthetic intermediates that react readily with heteroatom- and carbon-based nucleophiles in conventional substitution and catalytic cross-coupling reactions. − These compounds also can be accessed via radical-chain chlorination, , leveraging the comparatively low bond-dissociation energy and higher reactivity of benzylic C–H bonds (Figure A). However, radical-chain chlorination methods that involve chlorine radical (Cl · ) as the hydrogen-atom transfer (HAT) reagent, often exhibit poor C–H site selectivity.…”

“…However, radical-chain chlorination methods that involve chlorine radical (Cl · ) as the hydrogen-atom transfer (HAT) reagent, often exhibit poor C–H site selectivity. Consequently, benzylic chlorides are commonly prepared by the reaction of benzylic alcohols with SOCl 2 or via other functional-group interconversion methods. ,,,, C–H chlorination methods that employ species other than Cl · for the HAT step can show improved selectivity. − In this context, Cu catalysts, in combination with N -fluorobenzenesulfonimide as the oxidant (Cu/NFSI), promote diverse C–H functionalization and oxidative cross-coupling reactions (e.g., Figure B) − that exhibit high benzylic site selectivity. These methods involve a radical-relay mechanism, in which HAT generates a diffusible benzylic radical that undergoes subsequent functionalization by Cu II and a nucleophilic coupling partner.…”

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

“…To understand the function of the sulfinyl amine unit, two additional ligands L9 and L10 were tested. The results show that the chiral sulfinyl amine unit plays an important role in both reaction efficiency and good stereocontrol (L8 and L9), and we speculate that this amide might not function as a chiral anionic ligand like Liu's catalyst systems with ligand L4 because the difference in enantioselectivity was not obvious at 30 o C (L8 v.s L9) 22 . Later, we found that increasing the reaction temperature and using 90 W blue light can further improve the enantioselectivity, while retaining high yields (Fig.…”

“…Cobalt-catalyzed cross-couplings have been well-known as one of the most powerful approaches to forge chemical bonds 20 . However, as an important 3d-metal, cobalt has been much less studied for use in asymmetric radical couplings [21][22][23] than its neighbors, nickel 24 and copper 25,26 . Recently, metallaphotoredox-catalyzed radical cross-couplings that merge photoredox catalysis and 3d-metal catalysis have flourished 27 and again, cobalt 28 stands behind nickel and copper in its utilization.…”

Low-cost transition metal catalysed Negishi coupling: an update

“…A highly effective and enantioselective synthesis of 1,1-diarylmethanes 137 was established by Liu et al through Co-catalysed enantioconvergent Negishi coupling of aryl zinc chlorides 135 and benzyl chloride 134 . 48 This C(sp 3 )–C(sp 2 ) Negishi coupling afforded high yields of the coupled products 137 in the presence of 10 mol% of CoBr 2 and 15 mol% of an N , N , P -ligand 136 in toluene at 0 °C (Scheme 32). The present Cobalt-based catalytic system efficiently catalysed the Negishi coupling between differently substituted aryl benzyl chlorides and organozinc reagents to afford good to excellent yields.…”