Well-Defined Bis(NHC)Mn(I) Complex Catalyzed Tandem Transformation of α,β-Unsaturated Ketones to α-Methylated Ketones Using Methanol

Abstract

Tandem transformation of α,β-unsaturated ketones to α-methylated ketones by utilizing methanol as both the hydrogen and C1 sources is reported in the presence of a phosphine-free bis-N-heterocyclic carbene-Mn­(I) (bis-NHC-Mn­(I)) catalyst. The dehydrogenative coupling between methanol and α,β-unsaturated ketones produces the corresponding α-methylated ketones along with 1 equiv of formaldehyde and water. Among different bis-NHC-Mn­(I) complexes, the ethyl wingtip-substituted complex with a triflate counteranion showed the highest catalytic activity. This catalytic system was highly effective for the reductive methylation of a wide variety of substrates including aromatic, heteroaromatic, and aliphatic straight chains containing α,β-unsaturated ketones. Notably, this methodology led to the synthesis of pharmaceutically important drug molecules such as eperisone and lanperisone. Several control experiments, kinetic studies, Hammett studies, and density functional theory (DFT) calculations were carried out to understand this tandem catalytic process.

(NNC)Ru(II) Complex Catalyzed Selective Functionalization of Ketones with Methanol: Understanding the Role of Ancillary Ligands

“…Additionally, competitive kinetic isotope experiments were performed in the presence of 1:1 CH 3 OH and CD 3 OD, which revealed KIE values of 2, 2.7 and in the range of 2.3–2.6 for the transfer hydrogenation, α-methylation and the tandem synthesis of β-methylated alcohol, respectively (SI, sections 8.2, 8.4, and 8.5). These suggested that C–H bond breaking of methanol was one of the slow steps during both the transformations. ,, …”

“…These suggested that C−H bond breaking of methanol was one of the slow steps during both the transformations. 31,51,52 During both transfer hydrogenation as well as tandem βmethylation of 1 with methanol, an electronic effect was observed (Schemes 3 and 4). To comprehend the electronic effect, Hammett studies were carried out from the initial rates (within 60% conversion of the substrates) using various electronically disparate propiophenone derivatives (Figures 2e, 2f).…”

Bis-Triazolylidenes of Manganese and Rhenium and Their Catalytic Application in N-Alkylation of Amines with Alcohols

“…26 Later, other authors showed the capability of this complex to efficiently catalyze the N-alkylation of anilines with alcohols, 30a the α-alkylation of ketones with alcohols, 30b and, more recently, the transformation of α,βunsaturated ketones to α-methylated ketones using methanol. 31 Apart from classical imidazolium-derived NHCs, we are also interested in the chemistry of manganese with mesoionic carbenes (MICs). 32−35 MICs, especially those derived from 1,2,3-triazolylidenes, make up an interesting subclass of NHCs that have advanced to become a prominent class of ligands in catalysis.…”

“…With the aim of developing phosphine-free catalytic systems with cheap metals, our research team has recently focused on the preparation of active Mn catalysts using N-heterocyclic carbene ligands (NHCs). − Recently, we disclosed the excellent catalytic efficiency of fac -[Mn­(bis-NHC Me )­(CO) 3 Br], bearing a simple bidentate NHC in reduction reactions, namely, in hydrosilylation − and in the electrocatalytic reduction of CO 2 . Later, other authors showed the capability of this complex to efficiently catalyze the N-alkylation of anilines with alcohols, the α-alkylation of ketones with alcohols, and, more recently, the transformation of α,β-unsaturated ketones to α-methylated ketones using methanol . Apart from classical imidazolium-derived NHCs, we are also interested in the chemistry of manganese with mesoionic carbenes (MICs). − MICs, especially those derived from 1,2,3-triazolylidenes, make up an interesting subclass of NHCs that have advanced to become a prominent class of ligands in catalysis. − In many cases, their strong σ-donor and weak π-acceptor properties yield metal complexes with enhanced catalytic activities and stability .…”

Manganese(iii) complexes stabilized with N-heterocyclic carbene ligands for alcohol oxidation catalysis

“…1a, I-II) with a lack of organometallic species, for instance involving carbene ligands. Indeed, while several examples of manganese(I) N-heterocyclic carbene (NHC) complexes are known, [12][13][14][15][16][17][18] the NHC coordination chemistry has been investigated only scarcely with Mn in higher oxidation states. Especially manganese(III) NHC complexes are very rare, possibly due to the mismatch between the hard metal center and the soft carbene ligand.…”