The synthesis of 5- and 6-substituted quinuclidine-3-carboxylic esters: intermediates for novel muscarinic ligands
| Autor: | John Saunders, Richard H. Herbert, Kevin John Merchant, Raymond Baker, Ian J. Hunt, R. J. Snow |
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| Rok vydání: | 1991 |
| Předmět: | |
| Zdroj: | Journal of the Chemical Society, Perkin Transactions 1. :409 |
| ISSN: | 1364-5463 0300-922X |
| DOI: | 10.1039/p19910000409 |
| Popis: | Quinuclidine-3-carboxylic esters bearing 5-hydroxy, 5-methyl and 6-methyl substituents are of interest as precursors to novel muscarinic ligands. All diastereoisomers of these disubstituted quinuclidines have been prepared, in each case using an appropriately substituted quinuclidin-3-one as the key intermediate. The keto ester 5a was obtained stereoselectively, either by intramolecular alkylation of a bromoacetylpiperidine, or by Dieckmann cyclisation of the differentially protected piperidine 18. 5-Methylquinuclidin-3-one was formed as a single isomer 24b by Dieckmann cyclisation. Piperidine-2,4-diester 33, in contrast, yielded a mixture of 2,5-disubstituted quinuclidine isomers 34 on cyclisation. Elaboration of the quinuclidinones gave the required esters, in several cases with high stereoselectivity. The stereochemical outcome of the Dieckmann cyclisation has been rationalised on the basis of molecular mechanics calculations. |
| Databáze: | OpenAIRE |
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