Synthesis of cyclohexene substituted azaspirodien compounds by RCM and corresponding tetrahydrospirocyclopenta[c]pyrolidinone compound via PKR

The coverage of this context is related to the synthesis of several novel spirocyclic scaffolds containing nitrogen atom due to their importance in organic medicinal and pharmaceutical chemistry. Cyclohexenone and its derivatives were selected as starting materials due to the presence of these compounds in highly functionalized and important chiral bioactive compounds. First, cyclohexenone was reacted with allylamine or propargyl amine to form N-allyl imine and N-propargyl imine derivatives. Followed by the Grignard addition reaction with/without the protection of nitrogen atom to attain the corresponding diene and enyne structures. Ring Closing Metathesis (RCM) was applied on diene structures to finally attain the corresponding azaspiroundecadiene and azaspirodecadiene carboxylate with 81% and 78% respectively. On the other hand, Pauson-Khand reaction (PKR) was applied on enyne structures in the presence of cobalt carbonyl Co2(CO)8 and N-methyl morpholine N-oxide (NMO) to obtain cyclopenta[c]pyridinenone, cyclopenta[c]pyridinene carboxylate, and cyclopenta[c]pyrroline carboxylate skeletons with 67%, 75% and 65% chemical yields respectively. Finally, all compounds obtained in this context are novel from Imine to spirocyclic compounds and all reactions were carried out under nitrogen atmosphere (N2).