Palladium-Catalyzed Enantioselective Intramolecular Dearomative Heck Reaction

• Published in: Journal of the American Chemical Society Vol. 140; no. 42; pp. 13945 - 13951
• Main Authors: Li, Xiang, Zhou, Bo, Yang, Run-Ze, Yang, Fu-Ming, Liang, Ren-Xiao, Liu, Ren-Rong, Jia, Yi-Xia
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 24.10.2018; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; INTERMOLECULAR ARYLATIVE DEAROMATIZATION; CONSTRUCTION; DECALIN DERIVATIVES; ARYL; ASYMMETRIC HECK; QUATERNARY CARBON CENTERS; INDOLES; ACCESS; CYCLIZATION; REDOX-RELAY STRATEGY
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.8b09186

Enantioselective intramolecular dearomative Heck reactions have been developed by Pd-catalyzed cross-coupling of aryl halides or aryl triflates with the internal CC bond of indoles, benzofurans, pyrroles, and furans. A variety of structurally unique spiroheterocycles and benzofused heterocycles having N/O-substituted quaternary carbon stereocenters, and exocyclic olefin moieties were afforded in moderate to excellent yields with good to excellent enantioselectivities, showing a broad scope of the present protocol. A series of new BINOL- and H8-BINOL-based phosphoramidite ligands were synthesized and proved to be efficient chiral ligands in the reactions of C2-tethered substrates to form spiroheterocycles. (S)-SEGPHOS turned out to be a good ligand for the reaction delivering benzofused indolines and pyrrolines. Synthetic applications based on transformations of the exocyclic double bonds were realized without loss of enantiopurities, including hydrogenation, hydroborylation, and stereospecific ring-expanding rearrangement.