Towards Understanding the Mechanism of Intermolecular anti-Markovnikov Hydroamination of Unactivated Alkenes with Sulfonamides

Abstract

The intermolecular hydroamination transformation is highly sought in enantioselective organic synthesis because pre-existing methods for achieving this transformation are scarce, and those accessing anti-Markovnikov addition are even more rare. The Knowles lab has demonstrated that it is possible to achieve such a transformation with high enantioselectivity by using a chiral phosphate base to activate the N–H bond of a sulfonamide and form a chiral ion pair capable of undergoing enantioselective PCET. Although high enantiomeric excesses are observed, interactions between the starting material and catalysts have not been fully characterized. This work seeks to provide insight on the interactions between the sulfonamide, chiral phosphate base, and Iridium photocatalyst during the course of the catalytic cycle. Condition screens and Gaussian calculations were carried out to investigate the source of isomerization observed in starting material. NMR titrations and Stern-Volmer experiments were conducted as separate means for calculating the association constant of the pre-PCET sulfonamide-base adduct. Finally, synthesis of a phosphate base was attempted in preparation for crystal growth with the sulfonamide and photocatalyst. It was determined that both background isomerization processes and reversible C–N bond formation may contribute to observed isomerization, but no definite conclusions can be made. Stern-Volmer experimentation demonstrated strong binding in the pre-PCET adduct and a slightly inefficient PCET mechanism. Future work seeks to investigate the site of interaction between the catalyst and sulfonamide.