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The First Catalytic Highly Enantioselective Alkylation of Ketimines—A Novel Approach to Optically Active Quaternary α‐Amino Acids
Author(s) -
Saaby Steen,
Nakama Kimitaka,
Lie Mette Alstrup,
Hazell Rita G.,
Jørgensen Karl Anker
Publication year - 2003
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200305302
Subject(s) - enantioselective synthesis , chemistry , electrophile , imine , ligand (biochemistry) , catalysis , chiral ligand , alkylation , stereochemistry , absolute configuration , lewis acids and bases , medicinal chemistry , organic chemistry , biochemistry , receptor
A series of novel ketimines with intrinsic protecting group anchoring was synthesized and allowed to react with various silylketene acetals in the presence of 5–10 mol % of a chiral Zn(OTf) 2 ‐( R,R )‐Ph‐pybox‐aqua complex. The corresponding optically active quaternary α‐amino acid derivatives were obtained in high yields and with enantioselectivities ranging from 34 % up to 95 % ee . The catalyst was studied by 1 H NMR spectroscopy and X‐ray crystallography, and a dynamic equilibrium of two species was identified in solution. These are a homo‐chiral 1:2 metal–ligand complex and a 1:1 metal–ligand complex, of which the latter is expected to be the actual catalyst of the diastereo‐ and enantioselective reaction. A strong positive nonlinear effect was observed due to the formation of a catalytically inactive 1:2 metal–ligand hetero‐chiral complex. On the basis of DFT calculations and the absolute stereochemistry of the products, simultaneous coordination of the imino electrophile and a single molecule of H 2 O to the chiral Lewis acid complex is proposed. Coordination of the imine‐nitrogen atom in the axial position of an octahedral complex can account for the facial selectivity as well as the diastereoselectivity observed.