Aminosulf(ox)ides as ligands for Iridium(I)-catalyzed asymmetric transfer hydrogenation
A new class of efficient catalysts was developed for the asymmetric transfer hydrogenation of unsymmetrical ketones. A series of chiral N,S-chelates (6-22) was synthesized to serve as ligands in the iridium(I)-catalyzed reduction of ketones. Both formic acid and 2-propanol proved to be suitable as hydrogen donors. Sulfoxidation of an (R)-cysteine-based aminosulfide provided a diastereomeric ligand family containing a chiral sulfur atom. The two chiral centers of these ligands showed a clear effect of chiral cooperativity. In addition, aminosulfides containing two asymmetric carbon atoms in the backbone were synthesized. Both the sulfoxide-containing beta-amino alcohols and the aminosulfides derived from 1,2-disubstituted amino alcohols gave rise to high reaction rates and moderate to excellent enantioselectivities in the reduction of various ketones. The enantioselective outcome of the reaction was favorably affected by selecting the most appropriate hydrogen donor. Enantioselectivities of up to 97% were reached in the reduction of aryl-alkyl ketones.
Petra
DG
Institute of Molecular Chemistry, University of Amsterdam, Nieuwe Achtergracht 166, NL-1018 WV Amsterdam, The Netherlands, Bijvoet Center for Biomolecular Research, Padualaan 8, NL-3584 CH Utrecht, The Netherlands, and DSM Research, P.O. Box 18.
Kamer
PC
Spek
AL
Schoemaker
HE
van Leeuwen PW