Asymmetric Heck reaction mechanism

A key feature of the cationic mechanism is that removal (or dissociation) of an anionic ligand from the palladium coordination sphere allows alkene complexation to occur while maintaining coordination of both phosphines of a bisphosphine ligand. That both phosphines can be accommodated in a square-planar four-coordinate intermediate during the insertion step has provided a simple rationalization for the higher enantioselectivities often observed for the cationic pathway. Concrete information on the enantioselective step of asymmetric Heck reactions proceeding by the cationic pathway has not been reported to date. It is likely to be either coordination of the alkene to generate 20.S or the insertion step (20.5 —> 20.6, Scheme 8G.20). 

In 2006, Stephenson s group reported the involvement of a DKR process during an intramolecular asymmetric Heck reaction carried out in the presence of a BINAP-based Pd catalyst. It was shown that chiral helical conformations of the starting 2-iodoanilide interconverted through internal bond rotations, leading to the proposal of a DKR mechanism to account for the switch of the enantioselectivity (Scheme 2.61). 

Scheme 11.6 Mechanism of intermolecular asymmetric Mizoroki-Heck reaction of 2,3-dihydrofuran (1).

A detailed discussion of the current understanding of the mechanism of the Mizoroki-Heck reaction can be found in earUer chapters of this book and in several excellent reviews [7]. Two mechanistic pathways, typically termed neutral and cationic, have been proposed to account for the differences in reactivity and enantioselectivity observed in asymmetric Mizoroki-Heck cycUzations of unsaturated trillates and halides. These pathways differ in the degree of positive charge and the number of available coordination sites assignable to the palladium(II) intermediates of the catalytic cycle. Because catalytic asymmetric Mizoroki-Heck cyclizations are typically carried out with bidentate Ugands, these pathways will be illustrated with a chelating diphosphine Ugand. 

Scheme 1.2 The prototype asymmetric Heck-Mizoroki reaction and its proposed mechanism [12e, f, 13],...

This catalytic system allows three independent transformations to occur in sequence the Heck reaction, N-oxidation and asymmetric dihydroxylation (AD). The mechanism of the Heck reaction is discussed in the previous section. Here we take a closer look at the last two steps. They are coupled processes, based on the Sharpless asymmetric dihydroxylation reaction [22, 23]. Several recent reviews on Sharpless asymmetric dihydroxylation cover the general synthetic aspects [24-27], together with methods for immobilization of the osmium catalysts [28]. 

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