SYNTHESIS OF ENANTIOPURE PRIMARY AMINES BY STEREOSELECTIVE RING-OPENING OF CHIRAL OCTAHYDRO-1,3-BENZOXAZINES BY GRIGNARD AND ORGANOALUMINUMREAGENTS

Chiral 1,3-perhydrobenzoxazines 1, 2, and 9-14, prepared by condensati on of 8-(benzylamino)menthol with different aldehydes, react with alky lmagnesium bromides and trimethylaluminum leading to the open amino al cohols 3a-d, 4a-d, and 15-20 in excellent chemical yields and good to excellent diastereomeric excess. The sequential elimination of the men thol appendage by heating with P2O5 and the benzyl group by hydrogenol ysis lead to primary amines 7a-d, 8a-d, and 27-30 in excellent chemica l yields and ee. The addition of the alkyl group from the Grignard der ivatives and the methyl group from the trimethylaluminum occurs from o pposite sides of the heterocycle, yielding the final primary amines wi th the same stereochemistry.