The Synthesis of 2,3,3a,4,5,7a-Hexahydro-1H-inden-l-ols by Intramolecular Diels-Alder Reactions of l,3,8-Nonatrien-5-ols. Dependence of Product Stereochemistry on the Substitution Pattern

Alan P. Kozikowski, Werner Tückmantel

Research output: Contribution to journalArticlepeer-review

Abstract

A short and efficient synthesis of the title compounds is described, starting from readily available α,β-unsaturated carbonyl compounds 5 and β,γ-unsaturated ketones 4. Their directed aldol condensation yields the unsaturated hydroxy ketones 6 which are dehydrated to the trienones 7. Athough these fail to cyclize on heating, the intramolecular Diels-Alder reaction can be brought about after reduction or alkyllithium addition to the carbonyl group. Alkyl substitution in the positions 1, 2, 3, 5, and 7 has little influence on the ease and yield of cyclization, whereas a methyl group at C-4 hinders it considerably. The title compounds are obtained as mixtures of usually all four stereoisomers, of which one predominates (≥50%) in most cases. O-Alkylation in 8b has little effect on the isomer distribution. The major isomer of the 6-bromo derivative forms a highly crystalline p-nitrobenzoate 27, which permits stereochemical assignment through X-ray crystallography; for most other products assignments can be made by comparison and further evaluation of their 1H NMR spectra. The results are discussed in terms of a simple transition state model. The intramolecular Diels-Alder reaction fails when the length of the tethering chain is reduced by one, or when the diene unit becomes part of a furan ring. Trienones 7 are sensitive to autoxidation, of which some products are described.

Original languageEnglish (US)
Pages (from-to)2826-2837
Number of pages12
JournalJournal of Organic Chemistry
Volume56
Issue number8
DOIs
StatePublished - Apr 1 1991

ASJC Scopus subject areas

  • Organic Chemistry

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