Novel chiral pyridine N-oxide ligands and their application in the enantioselective catalytic reduction of ketones and the addition of diethylzinc toaldehydes

Starting from picolinic acids 3 and 4, the amino acid-derived 2-aminoacylpy ridine N-oxides 1a,c-e and 2,6-bis(aminoacyl)pyridine N-oxides 2b-e can be prepared in two steps by the coupling of picolinic acid N-oxides 5 and 6 un der Appel conditions with the corresponding L-amino acid ester or (1R,2S)-n orephedrine. Compounds 1 and 2 were used as chiral Ligands in two different asymmetric catalyses. In the catalytic addition of diethylzinc to benzalde hyde 11, low enantioselectivities (2-29% ee) were obtained regardless of th e amino acid moiety. However, the corresponding 2,6-bis(aminoacyl)pyridines 7 and 8 led to increased ee values (55% ee). In the catalytic reduction of ketones 9a-c to alcohols 10a-c low enantioselectivities were observed for alanine-, valine-, and leucine-derived N-oxides 1a,c and 2b,c. An increase of selectivity was observed for bis-methionine Ligand 2d (32-38% ee) relati ve to that of mono-methionine ligand Id (7-16% ee). However, mono-norephedr ine ligand le (less than or equal to 64% ee) and the corresponding bis-nore phedrine Ligand 2e (less than or equal to 51% ee) displayed the highest sel ectivities. The influence of the N-oxide moiety on the enantioselectivity w as demonstrated by the observation that 2,6-bis(aminoacyl)pyridines 7 and 8 gave much lower selectivities than the corresponding pyridine N-oxides 2d and e.