Cyclometalated Iridium-PhanePhos Complexes Are Active Catalysts in Enantioselective Allene-Fluoral Reductive Coupling and Related Alcohol-Mediated Carbonyl Additions That Form Acyclic Quaternary Carbon Stereocenters

Autor(es)

Schwartz, Leyah A. ^[1] ; Holmes, Michael ^[1] ; Brito, Gilmar A. ^[1] ; Goncalves, Theo P. ^{[2, 3]} ; Richardson, Jeffery ^[4] ; Ruble, J. Craig ^[5] ; Huang, Kuo-Wei ^{[2, 3]} ; Krische, Michael J. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Texas Austin, Dept Chem, Austin, TX 78712 - USA

^[2] KAUST, KAUST Catalysis Ctr, Thuwal 239556900 - Saudi Arabia

^[3] KAUST, Div Phys Sci & Engn, Thuwal 239556900 - Saudi Arabia

^[4] Eli Lilly & Co Ltd, Discovery Chem Res & Technol, Windlesham GU20 6PH, Surrey - England

^[5] Eli Lilly & Co, Discovery Chem Res & Technol, Indianapolis, IN 46285 - USA

• Tipo de documento: Artigo Científico
• Fonte: Journal of the American Chemical Society; v. 141, n. 5, p. 2087-2096, FEB 6 2019.
• Citações Web of Science: 16

Resumo

Iridium complexes modified by the chiral phosphine ligand PhanePhos catalyze the 2-propanol-mediated reductive coupling of diverse 1,1-disubstituted allenes 1a-1u with fluoral hydrate 2a to form CF3-substituted secondary alcohols 3a-3u that incorporate acyclic quaternary carbon-containing stereodiads. By exploiting concentration dependent stereoselectivity effects related to the interconversion of kinetic (Z)- and thermodynamic (E)-sigma-allyliridium isomers, adducts 3a-3u are formed with complete levels of branched regioselectivity and high levels of anti-diastereo-and enantioselectivity. The utility of this method for construction of CF3-oxetanes and CF3-azetidines is illustrated by the formation of 4a and 6a, respectively. Studies of the reaction mechanism aimed at illuminating the singular effectiveness of PhanePhos as a supporting ligand in this and related transformations have led to the identification of a chromatographically stable cyclometalated iridium-(R)-PhanePhos complex, Ir-PP-I, that is catalytically competent for allene-fluoral reductive coupling and previously reported transfer hydrogenative C-C couplings of dienes or CF3-allenes with methanol. Deuterium labeling studies, reaction progress kinetic analysis (RPKA) and computational studies corroborate a catalytic mechanism involving rapid allene hydrometalation followed by turnover-limiting carbonyl addition. A computationally determined stereochemical model shows that the ortho-CH2 group of the cyclometalated iridium-PhanePhos complex plays a key role in directing diastereo- and enantioselectivity. The collective data provide key insights into the structural-interactional features of allyliridium complexes required to enforce nucleophilic character, which should inform the design of related cyclometalated catalysts for umpoled allylation. (AU)

• Processo FAPESP: 17/00734-5 - Síntese catalítica de policetídios II via formação de ligação C-C mediada por hidrogênio
• Beneficiário: Gilmar Araujo Brito Junior
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado