New horizons in dirhodium(II) catalysis

Abstract

Cyclopropanes are versatile structural motifs found in pharmaceuticals, agrochemicals, and natural products. The synthesis of certain cyclopropane motifs in a stereoselective manner is challenging and therefore remains a focus point in asymmetric catalysis. One such challenging motif to obtain in an optically pure manner are 1,1-disubstituted (trifluoromethyl)cyclopropanes motifs. This thesis presents a new approach that employs a bench-stable carbene source in asymmetric cyclopropanation catalyzed by a [BiRh] paddlewheel complex, providing ready access to compounds of this type, which can be further derivatized. Additionally, a novel chiral dirhodium catalyst was developed, which bears its chirality on the metal centers themselves and not on the ligand sphere. This heterochiral-at-metal complex exhibited remarkable efficiency and selectivity in the asymmetric cyclopropanation of α-stannylated and α-trifluoromethylated diazoesters, providing products with excellent enantio- and diastereocontrol. DFT studies revealed that the amidate ligand plays a decisive role in stereocontrol through interligand hydrogen bonding and selective carbene formation at the [O₃N]-face of the catalyst. Furthermore, in a performed case study, the general widely held belief that carbene formation is the rate-determining step in the catalytic cycle of a cyclopropanation reaction could be debunked. Extensive DFT studies of an intramolecular cyclopropanation reaction with a heteroleptic amidate complex showed that the rate-determining step is the cyclopropanation event rather than carbene formation. This finding was verified by detection of the carbene intermediate under truly catalytic settings via in situ 13C NMR spectroscopy—an unprecedented experimental observation.