Mechanistic studies of Wacker-type amidocyclization of alkenes catalyzed by (IMes)Pd(TFA)2(H2O): kinetic and stereochemical implications of proton transfer.

The stereochemical course of the amidopalladation of alkenes has important implications for the development of enantioselective Pd-catalyzed "Wacker-type" oxidative amidation of alkenes. We have recently shown that the addition of base (Na2CO3) can alter the stereochemical course of amidopalladation in the (IMes)Pd(TFA)2(H2O)-catalyzed aerobic oxidative amidation of alkene. In this study, the mechanism of (IMes)Pd(TFA)2(H2O)-catalyzed oxidative heterocyclization of (Z)-4-hexenyltosylamide was investigated in the presence and absence of exogenous base Na2CO3. The results reveal two parallel pathways in the absence of base: a cis-amidopalladation pathway with turnover-limiting deprotonation of the sulfonamide nucleophile and a trans-amidopalladation pathway with turnover-limiting nucleophilic attack of sulfonamide on the coordinated alkene. The addition of base (Na2CO3) lowers the energy barrier associated with the proton transfer, leading to an overall faster turnover rate and exclusive cis-amidopalladation of alkene.