Enantiodivergent Pd-catalyzed C-C bond formation enabled through ligand parameterization.
Shibin ZhaoTobias GenschBenjamin MurrayZachary L NiemeyerMatthew S SigmanMark R BiscoePublished in: Science (New York, N.Y.) (2018)
Despite the enormous potential for the use of stereospecific cross-coupling reactions to rationally manipulate the three-dimensional structure of organic molecules, the factors that control the transfer of stereochemistry in these reactions remain poorly understood. Here we report a mechanistic and synthetic investigation into the use of enantioenriched alkylboron nucleophiles in stereospecific Pd-catalyzed Suzuki cross-coupling reactions. By developing a suite of molecular descriptors of phosphine ligands, we could apply predictive statistical models to select or design distinct ligands that respectively promoted stereoinvertive and stereoretentive cross-coupling reactions. Stereodefined branched structures were thereby accessed through the predictable manipulation of absolute stereochemistry, and a general model for the mechanism of alkylboron transmetallation was proposed.
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