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A β‐Enaminone‐Initiated Multicomponent Domino Reaction for the Synthesis of Indoloquinolizines and Benzoquinolizines from Acyclic Precursors
Author(s) -
Suryavanshi Padmakar A.,
Sridharan Vellaisamy,
Menéndez J. Carlos
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201204594
Subject(s) - chemistry , iminium , stereocenter , michael reaction , nucleophile , diastereomer , cascade reaction , nucleophilic addition , medicinal chemistry , domino , tryptamines , organic chemistry , stereochemistry , tryptamine , catalysis , enantioselective synthesis , biochemistry
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.