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A Stereodivergent–Convergent Chiral Induction Mode in Atroposelective Access to Biaryls via Rhodium-Catalyzed C–H Bond Activation

Panjie Hu, Bingxian Liu, Fen Wang, Ruijie Mi, Xiao‐Xi Li, Xingwei Li

2022ACS Catalysis22 citationsDOI

Abstract

Understanding the reaction mechanisms, particularly the chiral induction mode, is critical for the development of new asymmetric catalytic reactions. Rhodium(III)-catalyzed C–H activation en route to atroposelective [4 + 2] annulative coupling with α-diazo β-ketoesters has been realized, affording axially chiral phenanthrenes in good to excellent enantioselectivity. A combination of experimental and computational studies revealed a nontraditional stereodivergent–convergent chiral induction mode. The reaction proceeded with a rhodafluorene intermediate, followed by competitive, constructive, and stereodivergent migratory insertions of the two Rh–C(aryl) bonds into the carbene species to give β-ketoester intermediates. Then, the other Rh–C(aryl) bond migratorily inserts into the ketone carbonyl group. Following this stereodetermining carbonyl insertion, an ester-chelated rhodium(III) alkoxide species bearing two poorly controlled chiral centers and a well-controlled C(sp2)–C(sp3) chiral axis is generated. The final product is delivered via stereoconvergent elimination of a rhodium(III) species with retention of the well-controlled axial chirality and with loss of the central chirality.

Topics & Concepts

RhodiumChemistryAsymmetric inductionAtropisomerEnantioselective synthesisDiazoArylAxial chiralityChirality (physics)KetoneCatalysisStereochemistryKeteneMedicinal chemistryOrganic chemistryAlkylChiral symmetry breakingNambu–Jona-Lasinio modelQuantum mechanicsPhysicsQuarkAxial and Atropisomeric Chirality SynthesisCatalytic C–H Functionalization MethodsAlkaloids: synthesis and pharmacology