STEREOCONTROLLED SYNTHESIS OF CYCLIC ETHERS BY INTRAMOLECULAR HETERO-MICHAEL ADDITION .6. A COMPUTATIONAL STUDY OF THE ANNELATION TO 2,3-DISUBSTITUTED TETRAHYDROPYRANS

A computational study at the ab initio level of the cyclization of (E) - and (Z)-7-hydroxy-4-substituted-2,3-unsaturated esters leading to 2, 3-disubstituted tetrahydropyrans has been performed. The study showed the requirement of coordination between the pre-tetrahydropyranyl oxyg en and that of the carbonyl of the alpha,beta-unsaturated ester with t he cation of the base used to obtain a suitable transition state model . The calculations using the 6-31G//3-21G basis set show different re lative stabilities for the final products and transition states leadin g to them. The 6-31+G basis set was used as a calibration of the less energetic transition states. A model assuming a pre-chair conformatio n locating the chiral inductor equatorial and approaching the alpha,be ta-unsaturated ester in axial mode for the E isomer and equatorial for the Z geometry rationalizes the experimental results. The scape and l imitations of the model applied to 2,3,5,6-functionalized cases are di scussed.