Rhodium-Catalyzed Atroposelective Synthesis of Conformationally Stable C(sp 2 )–C(sp 3 ) Atropisomers via C–H Activation and Annulation with 9-Fluorenylacetylene
Abstract
C(sp 2 )–C(sp 3 ) axially chiral scaffolds represent an unusual class of atropisomeric systems. Given their low configurational stability, the asymmetric synthesis of C(sp 2 )–C(sp 3 ) atropisomers remains dauntingly challenging. Reported herein is the enantioselective synthesis of isoquinolones bearing both a C(sp 2 )–C(sp 3 ) axis and a proximal stereogenic center with a 5,6-ring linkage. This is realized via Rh(III)-catalyzed C–H activation of benzamides and [4 + 2] annulation with rationally designed 9-fluorenylacetylenes. The coupling system features mild, redox-neutral conditions and excellent enantioselectivity and diastereoselectivity. Migratory insertion into the alkyne has been established as both an enantio- and diastereodetermining step in the catalytic cycle.
Fields of Study & Subjects
Axial and Atropisomeric Chirality Synthesis
Catalytic C–H Functionalization Methods
Asymmetric Synthesis and Catalysis
Publication details
- Journal / source
- Organic Letters
- Publisher
- American Chemical Society (ACS)
- Volume
- 28
- Issue
- 13
- Pages
- 3973–3981
- Publication date
- 25 March 2026
- Language
- EN