Differentiation and functionalization of remote C–H bonds in adjacent positions

• Published in: Nature chemistry Vol. 12; no. 4; pp. 399 - 404
• Main Authors: Shi, Hang, Lu, Yi, Weng, Jiang, Bay, Katherine L., Chen, Xiangyang, Tanaka, Keita, Verma, Pritha, Houk, Kendall N., Yu, Jin-Quan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2020; NATURE PORTFOLIO; Nature Publishing Group
• Subjects: 639/638/403/933; 639/638/403/934; 639/638/549/933; 639/638/77; Analytical Chemistry; Bias; Biochemistry; Bonding agents; Carbon; Carbon - chemistry; Catalysis; Chemistry; Chemistry and Materials Science; Chemistry, Multidisciplinary; Chemistry/Food Science; Chemists; Coordination Complexes - chemistry; Differentiation; Functional groups; Hydrocinnamic acid; Hydrogen - chemistry; Hydrogen bonds; Inorganic Chemistry; Isoquinolines - chemistry; Leukemia; Molecular Structure; Norbornanes - chemistry; Organic Chemistry; Palladium; Palladium - chemistry; Physical Chemistry; Physical Sciences; Quinolines - chemistry; Science & Technology; Substrates; META; ACTIVATION; ARYLATION; LIGAND; PYRIDINES; SELECTIVE ALKYLATION; BORYLATION
• ISSN: 1755-4330; 1755-4349
• DOI: 10.1038/s41557-020-0424-5

Site-selective functionalization of C–H bonds will ultimately afford chemists transformative tools for editing and constructing complex molecular architectures. Towards this goal, it is essential to develop strategies to activate C–H bonds that are distal from a functional group. In this context, distinguishing remote C–H bonds on adjacent carbon atoms is an extraordinary challenge due to the lack of electronic or steric bias between the two positions. Herein, we report the design of a catalytic system leveraging a remote directing template and a transient norbornene mediator to selectively activate a previously inaccessible remote C–H bond that is one bond further away. The generality of this approach has been demonstrated with a range of heterocycles, including a complex anti-leukaemia agent and hydrocinnamic acid substrates. Distinguishing remote C–H bonds on adjacent carbon atoms is a fundamental challenge because of a lack of electronic or steric bias. Now, differentiation of distal C–H bonds that are adjacent to each other has been achieved by combining selective remote C–H activation—based on distance and geometry—with a norbornene-assisted palladium migration.