Scaffolding Ligand Directs Quaternary Carbon Synthesis

A bifunctional amine-phosphine ligand designed to simultaneously bind the substrate and catalyst in hydroformylation reactions is proving to be a versatile directing group for organic syntheses, report Kian L. Tan and coworkers at Boston College (J. Am. Chem. Soc., DOI: 10.1021/ja1036226). Tan’s group has previously shown how this so-called scaffolding ligand’s amine group helps bind an olefin substrate and the phosphine group helps bind a rhodium catalyst, leading to regio- and stereoselective hydroformylation of mono- or disubstituted olefins. Stoichiometric amounts of phosphorus-based directing groups were previously required to carry out such reactions, but by reversibly binding the substrate and catalyst, only a catalytic amount of the scaffolding ligand is needed. Tan, Xixi Sun, and Kwame Frimpong have now demonstrated that the scaffolding ligand selectively directs formation of a quaternary carbon, rather than preferentially forming a lactone, in the hydroformylation of styrene-based substrates (reaction shown, R = aryl groups). A general method of using hydroformylation to create highly substituted carbon centers in olefins had been lacking, the researchers note. The synthesis “demonstrates the power of directing groups to overturn inherent selectivities of reactions,” they write.