Although remarkable progress on palladium-catalyzed direct functionalization of inert C−H bonds has been made, the progress of catalytic enantioselective C−H activation has lagged behind. An impressive breakthrough came from Yu and co-workers, who developed a strategy which employs chiral monoprotected amino acids (MPAA) as efficient ligands to enable enantioselective C−H activation of an array of prochiral substrates.[1] Despite the more and more applications of MPAAs, the mechanism of how chiral MPAA control the enantioselectivity remains unclear. In this work, we conducted a combined ion-mobility mass spectrometry (IM-MS) and density functional theory (DFT) study to investigate the reaction mechanism and understand the origin of enantioselectivity. The model in which MPAA acts as bidentate ligand and carbonyl group in N-protecting group acts as proton acceptor[2] successfully accounts for the enantioselectivity. The enantioselectivity originates from the rigidity of the bidentate MPAA and substrates coordination. References: [1] (a) Shi, B.-F.; Zhang, Y.-H.; Lam, J. K.; Wang, D.-H.; Yu, J.-Q. J. Am. Chem. Soc. 2009, 132, 460. (b) Engle, K. M.; Yu, J.-Q. J. Org. Chem. 2013, 78, 8927. [2] Cheng, G.-J.; Yang, Y.-F.; Liu, P.; Chen, P.; Sun, T.-Y.; Li, G.; Zhang, X.; Houk, K. N.; Yu, J.-Q.; Wu, Y.-D. J. Am. Chem. Soc. 2014, 136, 894.

Insights into the enantioselectivity of monoprotected amino acid assisted C−H activation reaction

249th National Meeting (2015)

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