On the trans–cis controversy in Ti–TADDOLate-catalysed cycloadditions. Experimental indications for the structure of the reactive catalyst–substrate intermediate

Abstract

In order to investigate the structure of the reactive intermediate in the titanium-catalysed 1,3-dipolar cycloaddition, a series of reactions catalysed by TiX(PrⁱO)₃ and TiX(PrⁱO)-TADDOLate [X = Cl, Br, CF₃SO₃ (OTf)] complexes have been performed. The 1,3-dipolar cycloaddition between benzylidenephenylamine N-oxide and 3-[(E)-but-2′-enoyl]-1,3-oxazolidin-2-one is catalysed by 20 mol% TiCl(PrⁱO)₃ to give primarily the exo-isoxazolidine. If the chloride ligand of the catalyst is substituted with more bulky ligands such as bromide and trifluoromethanesulfonate, the selectivity of the reaction changes to give primarily the endo-isoxazolidine. The same change in diastereoselectivity from exo to endo is also observed by the application of TiX(PrⁱO)-TADDOLate (X = Cl, Br, OTf) complexes as catalysts for the analogous reaction. On the basis of these results, NMR spectral investigations and MM2 models, the most reactive intermediate in the TiCl(PrⁱO)₃ catalysed cycloaddition is proposed to be an octahedral complex in which the chloride ligand is located in the axial position relative to the plane defined by the two carbonyl oxygen atoms from 3-[(E)-but-2′-enoyl]-1,3-oxazolidin-2-one and two alkoxide ligands. The structure of the reactive intermediate in the Ti^IV-TADDOLate-catalysed 1,3-dipolar cycloaddition and Diels–Alder reactions is also briefly discussed on the basis of the results obtained.