Base-Mediated Nitrophenyl Reductive Cyclization for the Synthesis of Hexahydro-2,6-methano-1-benzazocines

A Diels–Alder reaction leading to 4-nitrophenylcyclohexanones
followed by a newly developed base-mediated reductive cyclization
of the resulting ketone tethered to the nitrobenzene moiety gives
access to the hexahydro-2,6-methano-1-benzazocine ring system present
in several biologically interesting natural products such as aspernomine.
The scope of the reaction was explored with eight substituted nitrobenzenes,
obtaining yields of up to 87%. The highest cytotoxicity was observed
in benzazocine 4h, bearing an enone moiety, which was
active against eight cancer cell lines.