Phenanthropiperidines and related compounds

Syntheses of variously substituted diphenylpiperidine derivatives were accomplished and their reactions, as intermediates in a new synthetic route to the physiologically active phenanthroindolizidine alkaloids and their analogues, were investigated. The s5nithesis involves Michael addition of phenylacetonitrile donors to ethyl cinnamate acceptors, yielding a series of ethyl-3,4-diphenyl-4-cyanobutanoates bearing aromatic methoxy, methylenedioxy and iodo substituents. Reductive cyclisation of these cyanoesters with Raney-nickel or copper chromite catalysts gave, imder exactly controlled conditions, either secondary or tertiary diphenylpiperidine derivatives or the corresponding dC - lactams. The ratio of the cis- and trans- racemates formed in each reaction was found to vary with changes in reduction temperature and with the substituent pattern of the starting material.