Catalytic enantioselective synthesis of tetrahydroisoquinolines and their analogues bearing a C4 stereocenter: formal synthesis of (+)-(8S,13R)-cyclocelabenzine.

A one-pot wonder: 1,2,3,4-Tetrahydroisoquinolines with a C4 stereocenter can be formed by using a one-pot multicomponent chiral phosphoric acid catalyzed transformation of a mixture of oxetane-tethered benzaldehydes, amines, and the dimethyl ester derivative of the Hantzsch ester (see scheme). This transformation can be used to prepare the spermidine alkaloid (+)-(8S,13R)-cyclocelabenzine.