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Computational Mechanistic Study of Stereoselective Suzuki Coupling of an α-Cyano-Activated Secondary Alkyl

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journal contribution
posted on 20.02.2016, 18:48 by Bimal Pudasaini, Benjamin G. Janesko
Palladium-catalyzed cross-couplings of secondary alkyls are promising tools for the stereoselective formation of carbon–carbon bonds. We report a computational mechanistic study of the stereoselective Suzuki coupling between (S)-2-chloropropanenitrile and phenylboronic acid, following a recent experimental report on related α-cyanohydrin triflates (J. Am. Chem. Soc. 2010, 132, 2524). Added Lewis base helps accelerate SN2 oxidative addition, leading to the experimentally observed inversion of configuration. Undesired β-hydride elimination side reactions are reduced by the activating cyano group’s inductive effects, by cyano-PdII coordination, and by excess boronic acid. The catalyst ligand’s trans influence and steric bulk also affect the rate of β-hydride elimination, suggesting design rules for alkyl cross-coupling ligands.