Asymmetric migratory insertion

Key words ONIOM, hydrogenation, enantioselectivity, asymmetric catalysis, DFT, reaction mechanism, chiral phosphine, ab initio, valence bond, oxidative addition, migratory insertion, reductive elimination. 

This mechanism differs from the commonly accepted mechanism of catalytic asymmetric hydrogenation, because the accepted one proposed an irreversible oxidative addition (the oxidative addition step should have the largest energy barrier), but it does agree with recent experimental results that show irreversible and stereodetermining migratory insertion [78]. 

The suggestion is then made that the stereoconlrolling step in asymmetric Mizoroki-Heck reactions is oxidative addition (via dynamic kinetic resolution) rather than alkene association or migratory insertion. The implication is that only substrates capable of a dynamic kinetic resolution may cyclize with high enantioselectivity. This would limit the substrate scope of the asymmetric intramolecular Mizoroki-Heck reaction. While the dynamic kinetic resolution during the oxidative addition may be a component of the overall stereoselectivity, it does not rule out contributions from later events in the mechanistic pathway and does not explain the effect of additives on selectivity. What has been shown is that the axial chirality of the o-iodoanilides (as with any enantioenriched isomer of a chiral precursor) influences the stereochemical outcome of their reactions. 

This fundamental experiment has strong implications on related catalyst-controlled Mizoroki-Heck cyclizations of precursors of this type. As axial chirality in 113 sets the stereochemistry in 114, enantioinduction was rationalized to arise from a dynamic kinetic resolution of (at elevated temperature) rapidly interconverting enanhomers of 113 in the oxidative addition step, rather than in the alkene coordination-migratory insertion event. Such a dynamic kinetic resolution process has been previously proposed by Stephenson et al. within their mechanistic study regarding the conformations of helically chiral 2-iodoanilides in intramolecular asymmetric Mizoroki-Heck reactions [72],... 

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