Site-Selective C–H Functionalization of N-Aryl and N-Heteroaryl Piperidines, Morpholines, and Piperazines Controlled by a Chiral Dirhodium Tetracarboxylate Catalyst

Abstract

Rhodium-catalyzed C–H insertion by donor/acceptor carbenes is a useful transformation in organic synthesis. However, the site-selectivity of the C–H transformation on the target molecule is often a major issue. Site-selective C–H functionalizations of challenging substrates like N-aryl- and N-heteroaryl piperidines could be achieved through chiral rhodium carbene intermediates, leading to the formation of highly stereoselective C-2 products. In addition, N-aryl morpholines and piperazines were selectively reacted at the α position to the N-aryl group.

Method Development and Syntheses Examples of Isotopically Labeled Compounds to Foster Operational Excellence in Pharma Industry

“…It illustrated the potential of C–H functionalization by donor/acceptor carbenes and demonstrated their potential for rapid synthesis of pharmaceutically relevant chiral scaffolds. 53…”

Ortho C–H Bond Activations in an Atmospheric Microwave Plasma Ion Source

“…Selective activation of C–H bonds is an important tool for organic chemical synthesis, widely used in natural product synthesis, − drug synthesis, and organic functional materials synthesis . However, selective activating of one of the numerous C–H bonds in organic compounds is challenging.…”

Better Together: Catalyzing Innovation in Organic Synthesis via Academic-Industrial Consortia

“…8 This fruitful collaboration encouraged AbbVie to initiate collaborations with nine other CCHF/CIC faculty, which have already resulted in several publications, 9 and the Davies group has expanded its industrial collaborative research to four other companies. 10 Funded The GICHF aimed to foster collaborative research between faculty and students across centers, with extensive industrial engagement in pharmaceutical, agrochemical, and material sciences. Collaboration opportunities were bolstered through international student exchange programs and workshops, like the one at KAIST, South Korea, which attracted around 110 participants from the U.S., South Korea, Japan, and Germany (Figure 4).…”