Asymmetric synthesis of 2-(alpha-aminoalkyl)oxazoles, 2-oxazolylpyrrolidines, 2-oxazolylpiperidines: Total synthesis of 4,5-dihydroxypipecolinic acid

Asymmetric alpha -alkylation of 2-aminomethyl-4,5-diphenyloxazole was achie ved by formation of azomethines 1 and ent-1 with the enantiomers of 2-hydro xypinan-3-one as chiral auxiliaries, reaction with alkylating reagents and final removal of the chiral auxiliary giving rise to optically active 2-(al pha -aminoalkyl)oxazoles 3, ent-3, 6 and 9. If alpha,omega -dihaloalkanes w ere used the resulting alkylation products could be further cyclized by int ramolecular alkylation of the amino group to afford optically active 2-oxaz olyl-N-heterocycles 4, ent-4, 7 and 10. The latter could be used for the to tal synthesis of naturally occurring 4,5-dihydroxypipecolinic acid 13.