Racemic Benzenesulfonohydrazide Enantioconvergent Tertiary C(sp3)-H Amination Catalyzed by Copper and Chiral Phosphoric Acid: Mechanistic Insights and Computational Prediction

Density functional theory computations reveal mechanistic insights into Cu and chiral phosphoric acid (CPA) catalyzed enantioconvergent amination of racemic benzenesulfonohydrazide. The O-O bond homolysis of tert-butyl 4-phenylbutaneperoxoate was found to be the turnover-limiting step with a total free energy barrier of 19.1 kcal/mol. The enantioconvergent amination is realized to obtain the same intermediate through prochiral carbon atom. The order and mode of hydrogen atom transferred by CPA and tert-butyloxy have a significant influence on the enantioselectivity and energy barriers. The olefinic side product generated by beta-hydride elimination is 9.9 kcal/mol thermodynamically less favourable. A series of phosphoric acids are predicted as promising co-catalysts with lower barriers for O-O bond homolysis.

Automated summary

Density functional theory computations provide mechanistic insights into Cu and chiral phosphoric acid (CPA) catalyzed enantioconvergent amination of racemic benzenesulfonohydrazide. The O-O bond homolysis of tert-butyl 4-phenylbutaneperoxoate is the turnover-limiting step with a total free energy barrier of 19.1 kcal/mol. Enantioconvergent amination is achieved by obtaining the same intermediate through a prochiral carbon atom. The order and mode of hydrogen atom transfer by CPA and tert-butyloxy significantly influence the enantioselectivity and energy barriers. The olefinic side product generated by beta-hydride elimination is thermodynamically less favorable by 9.9 kcal/mol. A series of phosphoric acids are predicted as promising co-catalysts with lower barriers for O-O bond homolysis.