Tandem transesterification and intramolecular cycloaddition of alpha-methoxycarbonylnitrones with chiral acyclic allyl alcohols: systematic studies on the factors affecting diastereofacial selectivity of the cycloaddition

Factors affecting the stereochemical course of the intramolecular cycloaddition of intermediary alpha-allyloxycarbonylnitrone resulting from transesterification of alpha-methoxycarbonylnitrones 1a-d with chiral allyl alcohols 5 or 6 were investigated systematically. It was found that the factors of diastereofacial selection are highly dependent on the geometries of the allyl alcohols. In the cases where primary or secondary chiral (Z)-allyl alcohols are used, A(1,3)-strain arising from the chiralities in the (Z)-nitrone transition states of the intramolecular cycloaddtion is the most important factor. In contrast, in the case of the reaction using chiral nitrones 1c,d and (E)-allyl alcohols, steric interaction between the chiral N-substituent and the trans substituent of the olefin moiety in the intermediate is dominant. These aspects were applied to geometry-differentiated cycloaddition using a mixture of (E)-5 and (Z)-5. As a typical example, treatment of bulky 1b with a 1:1 mixture of (E)-5 and (Z)-5 in the presence of a catalytic amount of TiCl(4) and MS 4A gave 7b as the predominant product among four possible products.