Nucleophilic addition to 3,4-cis-diacetyl-1,2,3,4-tetramethyl-1-cyclobutene: remarkably fast intramolecular hemiketalization

Reduction of 3,4-cis-diacetyl-1,2,3,4-tetramethyl-1-cyclobutene 1 with NaBH4 yielding 2-hydroxyoxolanes 2a and 2b with complete diastereoselectivity at the anomeric carbon atom suggests that a highly stereoselective intramolecular hemiketalization process leading to the formation of the 2-hydroxyoxolane unit is much faster than the attack of the second molecule of the nucleophile on the second carbonyl group. Further reduction of 2a at 0 °C gives selectively the meso-diol 3a. Reaction of 1 with MeLi or MeMgBr also involves the participation of the adjacent carbonyl, thereby yielding hydroxyoxolane 5a selectively. A mechanistic rationale is proposed on the basis of the relative energies of all isomeric hemiketals, 2a–d and 5a and b, (calculated by the PM3 method) and the relative stabilities of the conformers of 1 (calculated by the MM2 method).