Use of chiral-pool approach into -thieno analogues of the scarce bioactive phenanthroquinolizidine alkaloids.

The stereoselective synthesis of -thieno analogues of the phenanthroquinolizidine bioactive alkaloids (-)-Cryptopleurine and (-)-(15)-Hydroxycryptopleurine was achieved in five steps starting from easily available enantiopure ()-2-aminoadipic acid used as chiral pool and nitrogen atom source. During these investigations, both π-cationic cyclization of chiral -thienylmethyl-6-oxopipecolinic acids into pure ()-keto-lactams and theirs regioselective and diastereoselective reduction, considered as key steps of this sequence, were studied. Of particular interest, the Friedel-Crafts cyclization using (CFCO)O/BF·EtO show that near the expected keto-lactams, enamides and enamidones containing trifluoromethyl residue were isolated. A mechanism leading to the latter products with high synthetic potential was discussed.