Enantioselective Cobalt-Catalyzed Reductive Cross-Coupling for the Synthesis of Axially Chiral Phosphine–Olefin Ligands

Abstract

Transition-metal-catalyzed enantioselective cross-electrophile coupling reactions to construct C­(sp2)–C­(sp2) bonds remain a challenge. Herein, we report a general process for the enantioselective Co-catalyzed reductive cross-coupling reaction of o-(bromo)­arylphosphine oxide substrates and vinyl triflates, delivering axially chiral phosphine oxide compounds with good chemo- and enantioselectivity. A broad range of axially chiral compounds was obtained with excellent enantioselectivities, and the practical potential of this catalyst system was demonstrated by the versatile formation of axially chiral ligands and other functional atropisomers.

Theoretical Study on the Mechanism of Cobalt-Catalyzed C–O Silylation and Stannylation

“…The cobalt-catalyzed cross-coupling reaction of alkenyl acetates 4 with the Si–Zn reagent 15a was calculated. The results suggest that the spin state of Co­(bpy)Br 5c is a triplet, and the subsequent C–O oxidative addition to cobalt­(I) (via 3 TS-1a ) also occurs on the triplet free-energy profile (see Figures S3 and S4 in the Supporting Information for details). The subsequent Si–Zn reagent 15a and the intermediate 3 7a directly transmetallized because they contain two large groups Me 2 PhSi and OPiv; the two molecules are close to each other and cause large spatial obstacles.…”

Cobalt-Catalyzed Enantioselective Cross-Electrophile Couplings: Stereoselective Syntheses of 5–7-Membered Azacycles

“…Cobalt catalysts have been known to efficiently promote cross-electrophile couplings of two organic halides or other electrophiles in the presence of reductants, but enantioselective variants of these reductive couplings are still very limited . Recognizing this deficiency, we report herein a series of cobalt-catalyzed enantioselective cross-electrophile couplings of halodienes with aryl, heteroaryl, and alkenyl halides.…”

Nickel-Catalyzed Asymmetric Cross-Electrophile trans-Aryl-Benzylation of α-Naphthyl Propargylic Alcohols

“…Thus, XEC reactions are generally more desirable from the perspective of step economy and functionality tolerance in comparison with conventional redox-neutral cross-coupling reactions employing pregenerated organometallics. Over the past decade, considerable attention from organic chemists has been attracted to the development of asymmetric versions of XEC reactions, and impressive advances have been achieved in direct coupling between two organohalides, olefin difunctionalization, and ring-opening of strained cyclic molecules . Per our ongoing interest in developing asymmetric XEC reactions, − ,,, we envisioned an atroposelective cross-electrophile trans -dicarbofunctionalization of β-substituted α-naphthyl propargylic alcohols using aryl and benzyl halides as the coupling partners to access axially chiral allylic alcohols bearing a tetrasubstituted olefinic unit (Scheme C). , The challenges of this multiple-component reaction lie in the control of regioselectivity of two installed carbo-moieties, the E / Z selectivity of the C–C double bond, and the atroposelectivity of the chiral axis, as well as the suppression of potential two-component side reactions.…”