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

J Am Chem Soc. 2019 Feb 6;141(5):2087-2096. doi: 10.1021/jacs.8b11868. Epub 2019 Jan 25.

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)-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohols / chemistry*
  • Alkadienes / chemistry*
  • Allyl Compounds / chemical synthesis*
  • Allyl Compounds / chemistry
  • Carbon / chemistry*
  • Catalysis
  • Hydrocarbons, Fluorinated / chemistry*
  • Iridium / chemistry
  • Kinetics
  • Ligands
  • Molecular Structure
  • Organometallic Compounds / chemistry*
  • Oxidation-Reduction
  • Phosphines / chemistry
  • Stereoisomerism
  • Thermodynamics

Substances

  • Alcohols
  • Alkadienes
  • Allyl Compounds
  • Hydrocarbons, Fluorinated
  • Ligands
  • Organometallic Compounds
  • Phosphines
  • Iridium
  • Carbon
  • phosphine