Syntheses and applications of optical active bicyclic amino compounds

This article reviews for our two kinds of projects that lipase-catalyzed asymmetric resolution of bicyclic lactams, 3-oxo-2-azabicyclo[2.2.0]hex-5-enes and 2-azabicyclo[2.2.1]hept-5-en-3-ones, possessing synthetic versatility and the development of a new type of a bicyclic amine-based chiral ligand for a catalytic asymmetric synthesis. Thus, optically active 3-oxo-2-azabicyclo [2.2.0]hex- and 3-oxo-2-azabicyclo [2.2.1]hept-5-enes were obtained conveniently by lipase-catalyzed enantioselective acylation or hydrolysis of racemates, and absolute configurations were determined by chemical correlation, X-ray crystallographic and CD spectral analyses. Furthermore, optically active 2-azanorbornylmethanols, isoquinuelidinylmethanols, 2-azanorbornylmethanethiol, and isoquinuclidinylmethanethiol were prepared from ethyl (1S,3S,4R)-2-[(R)-1-phenylethyl]-2-azabicyclo [2.2. 1]hept-5-ene-3-carboxylate easily and their abilities as ligands were examined in the addition of diethylzinc to aldehydes to furnish secondary alcohols up to >99% ee. Particularly, 2-azanorbornylmethanethiol was the most effective as ligand in the alkylation.