Rhodium(I)/Chiral Diene-Catalyzed Asymmetric Carbene Transformations

ConspectusTransition-metal-catalyzed asymmetric carbene transformations enable efficient construction of chiral architectures for pharmaceutical and materials sciences. Chiral dirhodium(II) paddlewheel complexes, featuring d⁷-d⁷ dimeric cores, serve as privileged catalysts. Their electron-deficient character, enhanced by axial ligand withdrawal and weak π back-donation, generates highly electrophilic Rh(II)-carbenes, driving broad reactivity in cyclopropanation, C-H functionalization, X-H bond insertions, ylide formations, etc. In contrast, monovalent rhodium(I) complexes possess d⁸ square-planar centers with higher electron density. Through strategic ligand design, tunable σ/π-electron modulation can be achieved. Consequently, Rh(I)-carbenes are expected to exhibit attenuated electrophilicity and fine-tuned reactivity, thus enabling improved control over chemo-, regio-, and enantioselectivity. Despite this mechanistic promise, Rh(I)-carbene-mediated asymmetric catalysis remains conspicuously underexplored.This Account surveys the emerging frontier of Rh(I)-catalyzed asymmetric carbene transformations, spotlighting our development of Rh(I)/chiral diene catalysts in asymmetric carbene transformations. Early investigations of Rh(I)-carbene complexes centered primarily on <i>N</i>-heterocyclic carbene (NHC) ligands, leaving their catalytic potential in carbene transfer reactions unexplored. While initial studies established Rh(I)-carbenes' capability to mediate C-C bond formations, enantioselective X-H insertions had not been realized before 2015. In this context, our group successively developed the first Rh(I)-catalyzed asymmetric carbene insertions into B-H, Si-H, S-H, and O-H bonds, enabled by rationally designed chiral <i>C</i>₁- and <i>C</i>₂-symmetric diene ligands. This Rh(I)/diene catalytic system accommodates diverse carbene precursors, including aryl-, alkenyl-, and alkyldiazoacetates, -diazoketones, -diazophosphonates, and -diaryldiazomethanes. Beyond X-H insertions, we achieved the first example of regiospecific and direct enantioselective C(sp²)-H functionalizations of aniline derivatives and heteroarenes (unprotected indoles, pyrroles, furans) with arylvinyldiazoacetates. These reactions exhibited exceptional chemoselectivity by avoiding competitive O-H/N-H insertions. Molecular complexity was further accessed through a Rh(I)/organobase dual-catalytic cascade C-H functionalization/oxa-Michael addition, enabling the stereodivergent synthesis of dihydrobenzofurans. For cyclopropanation, our Rh(I)/chiral diene catalysts enabled >99% ee in intermolecular reactions with primary <i>N</i>-vinylamides and intramolecular cyclizations of trisubstituted allylic diazoacetates, providing the first general access to challenging cyclopropylamides and pentasubstituted cyclopropanes with contiguous stereocenters.Collectively, these advances establish Rh(I)-carbenes as uniquely tunable intermediates capable of reconciling electrophilicity with stereocontrol. By leveraging chiral diene ligands, Rh(I)-carbenes exhibit distinct mechanistic profiles compared to Rh(II) catalysis. Current progress provides a foundation for developing privileged chiral Rh(I) systems, and we envision that these insights will inspire innovative methodologies in target-oriented synthesis and advanced catalyst design.