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

Article abstract of DOI:10.1021/jo00008a045

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.Although 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 (>/- 50percent) 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.