A β‐Enaminone‐Initiated Multicomponent Domino Reaction for the Synthesis of Indoloquinolizines and Benzoquinolizines from Acyclic Precursors

The cerium(IV) ammonium nitrate (CAN)‐catalyzed sequential multicomponent reaction between tryptamine, α,β‐unsaturated aldehydes, and β‐dicarbonyl compounds affords highly substituted indolo[2,3‐ a ]quinolizines in a single synthetic operation. Two rings are generated through the creation of two CC and two CN bonds by a domino process comprising initial β‐enaminone formation, followed by individual Michael addition, 6‐ exo ‐ trig cyclization, iminium formation, and Pictet–Spengler steps. Furthermore, the reaction is diastereoselective and affords exclusively compounds with a trans relationship between the H‐2 and H‐12b protons. The use of amines bearing a less nucleophilic side chain aromatic ring (5‐bromotryptamine, 3,4‐dimethoxyphenylethylamine) prevents the Pictet–Spengler final step and leads to N ‐indolylethyl or N ‐phenylethyl‐1,4‐dihydropyridines, which are cyclized to the corresponding indolo[2,3‐ a ]quinolizines or benzo[ a ]quinolizines in the presence of HCl in methanol/water. Treatment of the fused quinolizine derivatives with sodium triacetoxyborohydride led to the corresponding indolo[2,3‐ a ]quinolizidines or benzo[ a ]quinolizidines, possessing four stereogenic centers, as mixtures of two diastereomers.