Mild N‑Arylation of Sulfoximines With (Hetero)aryl Chlorides Enabled by α-Methylnaphthyl-tBuBrettPhos Palladium
Sourav Manna1, Mahima Pilania1, Kumarjit Sen1
1Faculty of Chemistry and Biochemistry, Ruhr-Universität Bochum, Bochum, Germany.
Abstract:
N-Arylated sulfoximines are privileged motifs in pharmaceuticals, natural products, and chiral ligands, yet their synthesis remains challenging. We report a readily accessible, air- and moisture-stable precatalyst, [Pd(1-MeNAP)(tBuBrettPhos)]OTf, that promotes the N-arylation of NH-sulfoximines with exceptional efficiency. The mild conditions (Cs2CO3, 25°C) enable a broad substrate scope, tolerating e.g. aryl chlorides with free NH, OH, and COOH groups and sensitive, drug-like heterocycles, thereby allowing late-stage functionalization beyond current systems. Mechanistic studies reveal that the methylnaphthyl substituent and non-coordinating triflate counterion cooperatively accelerate precatalyst activation via transmetalation/reductive elimination, generating the active monoligated Pd(0) species even in the presence of weakly nucleophilic sulfoximines.
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