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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 8
Affiliation:
[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
Total Affiliations: 5
Document type: Journal article
Source: Journal of the American Chemical Society; v. 141, n. 5, p. 2087-2096, FEB 6 2019.
Web of Science Citations: 16
Abstract

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)

FAPESP's process: 17/00734-5 - Catalytic synthesis of Type II polyketides via Hydrogen-Mediated C-C bond formation
Grantee:Gilmar Araujo Brito Junior
Support type: Scholarships abroad - Research Internship - Post-doctor