Conjugate addition of 6-membered hydrazine to chiral tert-butyl (E)-2-(p-tolylsulfinyl) cinnamates.: Synthesis of (S)-celacinnine

Two enantiomers of the bicyclic lactam, (S)- and (R)-9-phenyl-1,6-diazabicyclo[4.3.0]nonan-7-one(6), were synthesized stereoselectively with high optical purity (95% ee) by the asymmetric conjugate addition-cyclization of piperidazine to chiral vinyl sulfoxides, tert-butyl (E)-2-[(R)-and (S)-p-tolylsulfinyl] cinnamate (4), followed by removal of the p-tolylsulfinyl group with SmI2. The subsequent reductive cleavage of the N-N bond of the bicyclic lactam 6 with sodium in liquid ammonia produced the corresponding 9-membered azalactam, (S)- and (R)-4-phenyl-1,5-diazacyclononan-2-one (7) with 99% and 97% ee, respectively. X-Ray crystallography showed that (S)- 7 exists exclusively as a trans conformer in the crystal state. Starting from (S)- 7, naturally occurring (S)-celacinnine 1 was synthesized with 99% ee employing the ring-expansion reaction via intramolecular transamidation.