Stereodivergent synthesis of all the four stereoisomers of antidepressant reboxetine

Chiral amino alcohol-copper(II) catalysts Cu-L-1c and Cu-ent-L-1c were utilized to promote the diastereo-selective nitroaldol reactions of chiral aldehydes (S)-3 or (R)-3 with nitromethane, which respectively led to the preferential formation of certain stereoisomer for nitro diol derivatives 4. Using this catalytic protocol, all the four stereoisomers of the antidepressant reboxetine were divergently prepared. The highest overall yield of this synthetic route reached up to 30.5% from aldehyde (S)-3.