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

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)-σ-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.