Science of Synthesis

Shibasaki, M.; Ohshima, T.; Itano, W., Science of Synthesis: Stereoselective Synthesis, (2011) 3, 489.

In contrast to electron-poor alkenes, the Mizoroki–Heck reaction using monodentate ligands and ligand-free conditions with electron-rich alkenes generally affords a mixture of the α- and β-products, in which the latter are formed as a mixture of E- and Z-isomers. In the cases of electron-rich enol ethers and enamides, the reaction proceeds through a “cationic pathway” with bidentate ligands (L—L), to afford, in general, the α-product ‌32‌ in a highly regioselective manner (‌Scheme 2‌). The “cationic pathway” is more sensitive to electronic rather than steric factors, whereas the “neutral pathway” is more sensitive to steric factors, thereby affording mixtures of α-product ‌32‌ and β-product ‌36‌. The cationic pathway is initiated with the dissociation of X from complex ‌26‌ to generate the tricoordinate 14-electron cationic complex ‌27‌ with the accompanying counterion X−. Complexation of electron-rich alkene ‌28‌ into the vacant coordination site provides the 16-electron species ‌29‌, which initiates insertion of the alkene into the Pd—R1 bond followed by re-formation of the Pd—X bond to give σ-alkylpalladium(II) complex ‌30‌. The corresponding neutral pathway occurs with the dissociation of one of the phosphines in the bidentate ligand to provide 14-electron neutral species ‌33‌. Association and complexation of the vacant coordination site in ‌33‌ with the alkene affords the 16-electron neutral species ‌34‌, which undergoes alkene insertion into the Pd—R1 bond and recomplexation of the previously displaced phosphine moiety to furnish a regioisomeric mixture of σ-alkenylpalladium(II) complexes ‌30‌ and ‌35‌. The nature of leaving group X (and thus the strength of the Pd—X bond) is clearly a critical issue. Aryl and alkenyl trifluoromethanesulfonates are generally assumed to follow the cationic pathway, whereas the corresponding halides follow the neutral pathway.

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References