TANDEM ALDOL-CYCLIZATION SEQUENCE FOR THE CONSTRUCTION OF CYCLIC ETHERS - THE FORMATION OF SUBSTITUTED TETRAHYDROFURANS

The application of a tandem deconjugative aldol-cyclization Sequence for the construction of substituted tetrahydrofurans was examined. The aldol condensation of alkenoates proceeded with alkylation at the alpha-position to generate homoallylic alcohol moieties. These compounds could be induced to cyclize under the influence of iodine via an endo mode. The stereoselectivity for the cyclization occurred in good to excellent fashion. X-ray crystal structure analysis of three of the tetrahydrofurans established unambiguously the product stereochemistry. This was: used to propose a transition structure for the cyclization which correctly predicts the observed product stereochemistry. By this method, virtually all the possible stereoisomers for the substituted tetrahydrofurans can be constructed by judicious choice of aldol product and/or olefin geometry.