N,O- vs N,C-Chelation in Half-Sandwich Iridium Complexes: A Dramatic Effect on Enantioselectivity in Asymmetric Transfer Hydrogenation of Ketones

Cyclometalation
of [Cp*IrCl2]2 with methyl
(S)-2-phenyl-4,5-dihydrooxazole-4-carboxylate in the presence of NaOAc
selectively led to a N,C- or N,O-chelated Cp*Ir­(III) complex, depending
on whether or not water was present in the reaction. While derived
from the same precursor, these two complexes behaved in a dramatically
different manner in asymmetric transfer hydrogenation (ATH) of ketones
by formic acid, with the N,O-chelated complex being much more selective
and active. The sense of asymmetric induction is also different, with
the N,O-complex affording S while the N,C-analogue R alcohols. Further
study revealed that the nature of the base additive considerably impacts
the enantioselectivity and the effective HCOOH/amine ratios. These
observations show the importance of ligand coordination mode and using
the right base for ATH reactions.