Enantioselective Preparation of Arenes with β‐Stereogenic Centers: Confronting the 1, 1‐Disubstituted Olefin Problem Using CuH/Pd Cooperative Catalysis. (30th June 2020)

• Record Type: Journal Article
• Authors: Lu, Zhaohong; Buchwald, Stephen L.
• Is Part Of: Angewandte Chemie. Volume 132:Number 37(2020)
• Page Start: 16262
• Page End: 16266
• Publication Date: 2020-06-30
• Subjects: asymmetric catalysis -- copper -- dual catalysis -- hydroarylation -- palladium; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202004414
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Arenes with β‐stereogenic centers are important substructures in pharmaceuticals and natural products. We have developed an asymmetric anti‐Markovnikov hydroarylation of 1, 1‐disubstituted olefins by dual palladium and copper hydride catalysis as a convenient and general approach to access these substructures. This efficient one‐step process addresses several limitations of the traditional stepwise approaches. The use of cesium benzoate as a base and a common phosphine ligand for both the Cu‐ and Pd‐catalyzed processes were important discoveries that allow these challenging olefin substrates to be efficiently transformed. A variety of aryl bromide coupling partners, including numerous heterocycles, were coupled with 1, 1‐disubstituted alkenes to generate arenes with β‐stereogenic centers. Abstract : It takes two : CuH/Pd‐catalyzed enantioselective hydroarylation of 1, 1‐disubstituted alkenes proceeds with anti‐Markovnikov regioselectivity under mild conditions to access β‐stereogenic arenes. A wide range of aryl bromides, including several heterocycle‐containing substrates, can be used with good efficiency and enantioselectivity. Various 1, 1‐disubstituted alkenes were also examined.