Decarboxylative Cyclizations and Cycloadditions of Palladium-polarized Aza-ortho-Xylylenes

Abstract

Previously we have shown that palladium catalysts effect the decarboxylation of vinyl oxazinones to form zwitterionic π-allyl palladium intermediates (A, Scheme 1).1 Thus, vinyl oxazinones can be equated with zwitterionic synthons (B). In the absence of other electrophiles, the zwitterionic intermediate cyclizes to form vinyl azetidines with high diastereoselectivity. Moreover, in the presence of suitably electrophilic Michael acceptors,2 the intermediates undergo diastereoselective cycloadditions to generate highly substituted piperidine derivatives.3

The related vinyl benzoxazinones (3) undergo similar palladium-induced decarboxylation (Scheme 2).4 However, these substrates give rise to aza-ortho-xylylene synthons (C).5 The decarboxylation of vinyl benzoxazinones under conditions of palladium catalysis occurs at 25 °C and is thus significantly milder than thermal decarboxylation of benzoxazinones which typically requires temperatures near 200 °C.6 In addition, the aza-ortho-xylylene equivalents generated in the presence of palladium are more polarized than standard aza-ortho-xylylenes. Thus, while standard aza-ortho-xylylenes preferentially react with electron rich olefins, palladium-polarized aza-ortho-xylylenes (D) prefer to react with electron deficient olefins. Herein, we further describe the cyclization and cycloaddition chemistry of these unique intermediates.