Addition reactions of protonic reagents to optically active 2-phenyl-1,3,2-oxazaborolines

Abstract

The addition reactions of water and methanol to (4R,5S)-4-methyl-2,5-diphenyl-1,3,2-oxazaboroline 1 (derived from (+)-norephedrine), (4R,5S)-(+)-3,4-dimethyl-2,5-diphenyl-1,3,2-oxazaboroline 2 (derived from (+)-ephedrine) and to (4R,5R)-(+)-3,4-dimethyl-2,5-diphenyl-1,3,2-oxazaboroline 3 (derived from (+)-pseudoephedrine) were studied. The reactions gave the corresponding (N-B)-phenyl(2-aminoethoxy)boronic acids (4-6) or methyl esters (7-9). In 4 and 7 the boron atom is a stereogenic center, therefore two diasteromeric derivatives are expected. In compounds 5, 6, 8 and 9 both nitrogen and boron atoms are stereogenic centers and four diasteromers are possible. The structures of the addition products have been established by 1H-, 11B- and 13C-NMR, and that of compound 6 by X-ray diffraction analysis. The reactions with methanol gave only one isomer (7-9). The reaction of 1 with water afforded both boron epimers (50/50 ratio). The reaction of 2 with water observed at −50° showed both B-epimers in 80/20 ratio, whereas the same reaction with 3 gave only one isomer. In all cases the main isomer has the N-methyl trans to the C-methyl group and the B-phenyl cis to the N-methyl group. The X-ray diffraction molecular structure of compound 6 [(4R,5R)-(+)-3,4-dimethyl-2,5-diphenyl-2-hydroxy-1,3,2-oxazaborolidine], confirmed the structure assignment made from the NMR data. Addition reactions to 1,3,2-oxazaborolines are an efficient method to introduce stereoselectively functional groups to boron atom in order to obtain new boron heterocycles.