Sustainable and Selective Monomethylation of Anilines by Methanol with Solid Molecular NHC-Ir Catalysts

Abstract

Using feedstock methanol as a green methylation reagent, the selective N-monomethylation of anilines is realized under mild reaction conditions by using N-heterocyclic carbene iridium (NHC-Ir) coordination assemblies as highly efficient solid molecular catalysts. Along with a broad substrate scope and good functional group tolerance, up to quantitative yield and 2.0 × 104 turnover numbers (TONs) are obtained even at low catalyst loadings. Notably, the solid NHC-Ir molecular catalyst can be easily recovered and recycled more than 20 times without obvious loss of reactivity and selectivity. Furthermore, this selective practical protocol can be successfully extended to direct methylation of highly functionalized bioactive compounds including 3-aminoestrone, cinacalcet, and their analogues in excellent yields and selectivities, highlighting their potential application in pharmaceuticals.