Mechanistic Insights into Asymmetric C-H Insertion Cooperatively Catalyzed by a Dirhodium(II) Complex and Chiral Phosphoric Acid

The reaction mechanism of methyl 2-diazo-2-phenylacetate (PIA) with 1-phenylpyrrolidine (An) cooperatively catalyzed by a dirhodium(II) complex and chiral spirophosphoric acid (SPA) has been studied with the aid of DFT methods. The results show that the nucleophilic attack of An at the in situ generated carbenoid is preferred to give a metal-associated enol intermediate. In addition, a stronger interaction between the dirhodium(II) complex and molecules such as the enol and chiral spirophosphoric acid is better for the asymmetric C-H insertion. This is due to the fact that a stronger interaction can restrict the chiral spirophosphoric acid around the dirhodium(II) complex: In this case, the dissociated enol can be captured by chiral spirophosphoric acid immediately to give the major S-enantiomer product. Otherwise, the dimerization of enol molecules will occur followed by a self-catalyzed process to give the racemic C-H insertion product. This finding should be important for the design of other related dual catalyses in the future.