Electronic differentiations in palladium-catalyzed allylic substitutions

The “trans rule” in Pd-catalyzed allylic substitutions predicts trans to phosphorus additions of nucleophiles to Pd–allyl intermediates, e.g., with P,N-ligands. This computational study reveals that not only the intrinsic electronic differentiation between P- (i.e., PH3) and N-ligands (i.e., para-X-substituted pyridines), but also the “late” or “early” nature of the transition structures is crucial for strong cis vs. trans discriminations and hence for selectivity. Although para-nitro pyridine exhibits less intrinsic electronic differentiation than para-dimethylamino pyridine, the higher reactivity of the Pd–allyl-intermediate and the earlier nature of the transition structure yield a higher sensitivity for electronic differentiation for Xdouble bond; length as m-dashNO2 than Xdouble bond; length as m-dashNMe2.