Rhodium‐Catalyzed Enantioselective Synthesis of Planar‐Chiral Macrocycles via De Novo Isoquinoline Formation
Abstract
ABSTRACT De novo formation of the aromatic ring is an attractive strategy for atroposelective synthesis, but its application to planar‐chiral macrocycles remains challenging. Herein, we report a rhodium‐catalyzed enantioselective synthesis of planar‐chiral macrocycles via de novo isoquinoline construction. This method is characterized by high levels of enantioselectivity (up to 96% ee), regioselectivity (up to >20:1 rr), and functional group tolerance, providing a series of isoquinoline‐based macrocyclic atropisomers. Furthermore, the synthetic utility of this protocol is validated via a mmol‐scale reaction and post‐modification process of the product. Mechanistic studies, including deuterium labeling, kinetic isotope effect, and DFT calculations, support C─H bond cleavage as the rate‐determining step and elucidate the origin of the stereoselectivity.
Article Details
Authors (5)
Bo‐Bo Gou
New Cornerstone Science Laboratory State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences Shanghai China
Wen‐Jie Shen
New Cornerstone Science Laboratory State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences Shanghai China
Qing Gu
New Cornerstone Science Laboratory, State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China
Yuan‐Jun Gao
New Cornerstone Science Laboratory State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences Shanghai China
Shu‐Li You
New Cornerstone Science Laboratory State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences Shanghai China