Towards a total synthesis of quinocarcin:: Diastereoselective synthesis of functionalized azepino[1,2-b]isoquinolines

1,3-Disubstituted tetrahydro-oxazolo-isoquinolinones 19a,b were obtained from phenylalanine in seven steps and 42% overall yield by Katritzky's benzotriazole method. The tricyclic oxazolidinone 19a was further converted into amino alcohol 10 by employing a chemoselective reduction of the ester group with LiBH4/MeOH. Compound 10 and the corresponding 1-unsubstituted tetrahydroisoquinoline alcohol 11 were converted into aldehydes 27 and 33, which cyclized in the presence of different Lewis acids to give the substituted azepino[1,2-b]isoquinolines 34 and 35, respectively, which are key structural features of the alkaloid quinocarcin. The stereoselectivities of the Lewis-acid-catalyzed heteroene reaction are highly dependent on the substitution pattern and the type of Lewis acid. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).