The synthesis of phenanthropiperidines

In order to develop a facile preparative method for the synthesis of the physiologically active alkaloid tylocrebrine and its analogues, and to further examine the relationships between chamical structure and physiological activity, a new approach to the preparation of phenanthropiperidines and phenanthroindolizidines was devised and investigatedo Michael reactions between methoxyl substituted ethyl cinnamates and phenylacetonitriles proceeded smoothly to yield four new ethyl- if -cyano- ^ , ^ - diphenylbutyrateso These compounds underwent- reductive cyclisation by catalytic high pressure hydrogénation to give the corresponding N-ethyl 3, 4-diphenylpiperidines in good yield. The mechanism of the reduction reaction was elucidated and found to proceed via an oC -piperidone, which is further reduced to a secondary amine, and then alkylated at the nitrogen by the alcohol present as solvent©