Diastereoselectivity of isoxazolidines obtained from α,α-diphenylprolinol trimethylsilyl ether-catalyzed three-component domino reactions

Theoretical calculations employed to investigate the diastereoselectivity of isoxazolidines and bicyclic [3,3,0]-isoxazolidines, obtained from the α,α-diphenylprolinol trimethylsilyl ether-catalyzed three-component domino reactions, revealed two different functions of the catalyst. In the synthesis of bicyclic [3,3,0]-isoxazolidine compounds, the catalyst's role was to facilitate the initial Michael reaction, but did not influence the stereochemistry of the bicyclic [3,3,0]-isoxazolidine. In the synthesis of isoxazolidines, the catalyst was involved in controlling the stereogenic centers on the isoxazolidine through hydrogen bonding and steric effects in the 1,3-dipolar cycloaddition step. Insights gained from our mechanistic investigations have enabled us to propose a scheme for the synthesis of bicyclic [3,3,0]-isoxazolidine compounds bearing six stereogenic centers.