A Proton-Responsive Pyridyl(benzamide)-Functionalized NHC Ligand on Ir Complex for Alkylation of Ketones and Secondary Alcohols

A Cp*Ir(III) complex (1) of a newly designed ligand L-1 featuring a proton-responsive pyridyl(benzamide) appended on N-heterocyclic carbene (NHC) has been synthesized. The molecular structure of 1 reveals a dearomatized form of the ligand. The protonation of 1 with HBF4 in tetrahydrofuran gives the corresponding aromatized complex [Cp*Ir((LH)-H-1)Cl]BF4 (2). Both compounds are characterized spectroscopically and by X-ray crystallography. The protonation of 1 with acid is examined by H-1 NMR and UV-vis spectra. The proton-responsive character of 1 is exploited for catalyzing alpha-alkylation of ketones and beta-alkylation of secondary alcohols using primary alcohols as alkylating agents through hydrogen-borrowing methodology. Compound 1 is an effective catalyst for these reactions and exhibits a superior activity in comparison to a structurally similar iridium complex [Cp*Ir(L-2)Cl]PF6 (3) lacking a proton-responsive pendant amide moiety. The catalytic alkylation is characterized by a wide substrate scope, low catalyst and base loadings, and a short reaction time. The catalytic efficacy of 1 is also demonstrated for the syntheses of quinoline and lactone derivatives via acceptorless dehydrogenation, and selective alkylation of two steroids, pregnenolone and testosterone. Detailed mechanistic investigations and DFT calculations substantiate the role of the proton-responsive ligand in the hydrogen-borrowing process.

Automated summary

A newly designed ligand L-1 featuring a proton-responsive pyridyl(benzamide) appended on N-heterocyclic carbene (NHC) has been used to synthesize a Cp*Ir(III) complex (1), which exhibits superior catalytic activity in alpha-alkylation of ketones and beta-alkylation of secondary alcohols. The proton-responsive ligand is also demonstrated to be effective in the synthesis of quinoline and lactone derivatives, as well as the selective alkylation of two steroids, pregnenolone and testosterone. Detailed mechanistic investigations and DFT calculations support the role of the proton-responsive ligand in the hydrogen-borrowing process.