Impact Factor:16.1
DOI number:10.1021/jacs.6c08309
Journal:J. Am. Chem. Soc
Abstract:Oxa-quaternary carbon centers are prevalent in bioactive natural products and pharmaceuticals. However, the development of general and practical methods to construct these oxa-quaternary carbon stereocenters remains a formidable challenge. Herein, we report a desymmetrization strategy for the construction of oxa-quaternary carbon stereocenters based on palladium/chiral norbornene cooperative catalysis. With readily available aryl iodides and prochiral 2’-bromo-aryl-substituted tertiary alcohols as the building blocks, a wide variety of 6H-benzo[c]chromenes bearing an oxa-quaternary carbon stereocenter and a versatile C–Br bond are expediently prepared in a highly enantioselective manner (43 examples, up to 99% e.e.). Notably, both enantiomers can be stereodivergently obtained through a simple switch of the same configurated chiral NBE cocatalysts. The synthetic utility of this method is demonstrated by a successful scale-up experiment and diverse late-stage structural modifications through the facile elaboration of the common C–Br bond of the obtained chiral 6H-benzo[c]chromene products. In addition to the experimental studies, DFT calculations are performed to elucidate the reaction mechanism, the origin of enantiodiscrimination, and enantioselectivity inversion in this desymmetrization process.
Indexed by:Journal paper
Discipline:Natural Science
ISSN No.:0002-7863
Translation or Not:no
Date of Publication:2026-06-09
Included Journals:SCI
Links to published journals:https://pubs.acs.org/doi/10.1021/jacs.6c08309
Date of Publication:2026-06-09