Highly diastereoselective formation of bicyclic compounds by intramolecular cycloaddition of chiral thiaalkenyl nitrones

Abstract

Starting from chiral mercapto alcohols 5 in several reaction steps nitrones 7 were formed which underwent spontaneously intramolecular cycloaddition to give diastereomerically pure products 8. However, during the reaction course partial racemization had occurred. In contrast, nitrones 9 in which the chiral center is adjacent to the nitrogen atom afforded a mixture of the two diastereomeric cycloadducts 10 and 11. Compound 14 was synthesized from the homochiral amino diol 12 with retention of configuration at the two chiral centers. 14 was converted to the alcohol compounds 15, 19 and 20. These were subjected to Swern oxidation followed by treatment with N-alkyl or N-arylhydroxylamines. The nitrones formed in this way underwent spontaneously intramolecular cycloaddition to afford the diastereomerically and enantiomerically pure bicyclic products 17, 21 and 22, respectively.