Design of catalysts for site-selective and enantioselective functionalization of non-activated primary C–H bonds

• Published in: Nature chemistry Vol. 10; no. 10; pp. 1048 - 1055
• Main Authors: Liao, Kuangbiao, Yang, Yun-Fang, Li, Yingzi, Sanders, Jacob N., Houk, K. N., Musaev, Djamaladdin G., Davies, Huw M. L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2018; Springer Nature; Nature Publishing Group
• Subjects: 639/638/403/933; 639/638/77/883; Analytical Chemistry; Biochemistry; Carbenes; Catalysis; Catalysts; Chemical synthesis; Chemistry; Chemistry and Materials Science; Chemistry, Multidisciplinary; Chemistry/Food Science; Enantiomers; Functional groups; Inorganic Chemistry; Intermediates; Organic Chemistry; Physical Chemistry; Physical Sciences; Rhodium compounds; Science & Technology; Selectivity; Stereoselectivity; CARBENE; ACTIVATION; AMINATION; METHYL ARYLDIAZOACETATES; ASYMMETRIC-SYNTHESIS; SYN-ALDOL PRODUCTS; INSERTION REACTIONS; THREO-METHYLPHENIDATE; LATE-STAGE FUNCTIONALIZATION; PHOTOREDOX CATALYSIS
• ISSN: 1755-4330; 1755-4349; 1755-4349
• DOI: 10.1038/s41557-018-0087-7

C–H functionalization represents a promising approach for the synthesis of complex molecules. Instead of relying on modifying the functional groups present in a molecule, the synthetic sequence is achieved by carrying out selective reactions on the C–H bonds, which traditionally would have been considered to be the unreactive components of a molecule. A major challenge is to design catalysts to control both the site- and stereoselectivity of the C–H functionalization. We have been developing dirhodium catalysts with different selectivity profiles in C–H functionalization reactions with donor/acceptor carbenes as reactive intermediates. Here we describe a new dirhodium catalyst capable of the functionalization of non-activated primary C–H bonds with high levels of site selectivity and enantioselectivity. Catalyst-controlled site selectivity without relying on the influence of a directing group within the substrate is a major challenge in C–H functionalization. Now a catalyst is described that selectively functionalizes non-activated primary C–H bonds in the presence of a variety of other C–H bonds and functional groups.