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Synthesis of Benzo[ c ]azocanones and Indeno[1,2‐ b ]pyrroles from Oxoindanecarboxylates
Author(s) -
Behler Florian,
Habecker Florian,
Saak Wolfgang,
Klüner Thorsten,
Christoffers Jens
Publication year - 2011
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201100289
Subject(s) - chemistry , conformational isomerism , stereochemistry , diastereomer , carboxylate , methylamine , acetylacetone , cyclopentanone , nuclear magnetic resonance spectroscopy , medicinal chemistry , molecule , organic chemistry , catalysis
Ethyl 1‐oxo‐indane‐2‐carboxylate with a 1,4‐diketone motif gave a benzo[ c ]azocane‐1‐one derivative ― an eight‐membered ring lactam ― in a bismuth‐mediated ring‐expansion reaction with methylamine (40 % yield). Yields with other primary amines were significantly lower. The ester function in the heterocyclic product could be saponified to give the free carboxylic acid, which was further amidated with para ‐bromoaniline. The molecular structure of the latter was established by X‐ray single‐crystal analysis. Benzo[ c ]azocanones exist in two diastereoisomeric conformations, causing double signal sets in the NMR spectra. Slow interconversion between these conformers was proved by EXSY NMR spectroscopy. Moreover, a conformational analysis by DFT calculations revealed the two diastereoisomers to be boat conformers that interconvert through a twist conformer. The maximum barrier for this process was calculated to be approximately 70 kJ/mol. Reaction of the corresponding methyl 1‐oxoindane‐2‐carboxylate with methylamine gave the benzo[ c ]azocanone in lower yield. A spirolactam and an indeno[1,2‐ b ]pyrrole were formed as further products. When using an indanone‐derived 1,4‐diketone without an ester function, several primary amines could be used in a bismuth‐catalyzed Paal–Knorr reaction to give indeno[1,2‐ b ]pyrrole derivatives with up to quantitative yields in several cases. Attempts to synthesize a caprolactam derivative from a cyclobutanone derived β‐oxo ester with 1,4‐diketone motif were unsuccessful.