C-Methylation of Alcohols, Ketones, and Indoles with Methanol Using Heterogeneous Platinum Catalysts

Abstract

A versatile, selective, and recyclable heterogeneous catalytic method for the methylation of C–H bonds in alcohols, ketones, and indoles with methanol under oxidant-free conditions using a Pt-loaded carbon (Pt/C) catalyst in the presence of NaOH is reported. This catalytic system is effective for various methylation reactions: (1) the β-methylation of primary alcohols, including aryl, aliphatic, and heterocyclic alcohols, (2) the α-methylation of ketones, and (3) the selective C3-methylation of indoles. The reactions are driven by a borrowing-hydrogen mechanism. The reaction begins with the dehydrogenation of the alcohol(s) to afford aldehydes, which subsequently undergo a condensation reaction with the nucleophile (aldehyde, ketone, or indole), followed by hydrogenation of the condensation product by Pt–H species to yield the desired product. In all of the methylation reactions explored in this study, the Pt/C catalyst exhibits a significantly higher turnover number than other previously reported homogeneous catalytic systems. Moreover, it is demonstrated that the high catalytic activity of Pt can be rationalized in terms of the adsorption energy of hydrogen on the metal surface, as revealed by density functional theory calculations on different metal surfaces.

Beyond Friedel and Crafts: Directed Alkylation of C−H Bonds in Arenes

“…In addition to alkenes,a lkyl halides,a nd cross-dehydrogenative coupling reactions,s ome other alkylating reagents have also been exploited for the direct and selective alkylation of electron-rich heteroarenes:t hese include alcohols, [155][156][157][158] carboxylic acids, [159] peroxides, [160] pyridinium salts, [90] N,N-dialkylanilines, [161] and carboxylic xanthates. [97,98,162] Theuse of alcohols as alkylating agents has been elegantly exploited by Yi for the ruthenium-catalyzed direct alkylation of alkenes with ac ationic ruthenium hydride complex [(C 6 H 6 )(PCy 3 )(CO)RuH] + BF 4 À .…”

“…[155] Although mainly focused on the direct alkylation of alkenes,t he direct alkylation of benzofuran and N-methylindole using some aliphatic or benzylic alcohols has also been shown to proceed with high efficiency.M ore recently,h eterogeneous platinum catalysts have been shown by Shimizu to promote the C3-selective methylation of indoles with methanol (Scheme 55). [156] The reaction is likely to proceed through ah ydrogen borrowing type mechanism involving oxidation of methanol to formaldehyde and subsequent condensation on the indole followed by hydrogenation of the condensation product by aplatinum hydride species.O verall, the desired C3-methylindoles are obtained with high efficiency, with the exception of Nmethylindole,w hich was found to be unreactive.T he same transformation could also be achieved using Co(BF 4 ) 2 ·6 H 2 O and P(CH 2 CH 2 PPh 2 ) 3 as the catalytic system. [157] Finally,t he alkylation (mostly benzylation) of pyrroles with primary alcohols through ab orrowing hydrogen mechanism was also achieved using iridium P, N,P-pincer complexes.…”

Beyond Friedel and Crafts: Innate Alkylation of C−H Bonds in Arenes

“…In addition to alkenes, alkyl halides, and cross‐dehydrogenative coupling reactions, some other alkylating reagents have also been exploited for the direct and selective alkylation of electron‐rich heteroarenes: these include alcohols, carboxylic acids, peroxides, pyridinium salts, N , N ‐dialkylanilines, and carboxylic xanthates …”

“…Although mainly focused on the direct alkylation of alkenes, the direct alkylation of benzofuran and N ‐methylindole using some aliphatic or benzylic alcohols has also been shown to proceed with high efficiency. More recently, heterogeneous platinum catalysts have been shown by Shimizu to promote the C3‐selective methylation of indoles with methanol (Scheme ) . The reaction is likely to proceed through a hydrogen borrowing type mechanism involving oxidation of methanol to formaldehyde and subsequent condensation on the indole followed by hydrogenation of the condensation product by a platinum hydride species.…”

Recent Advances in Methylation: A Guide for Selecting Methylation Reagents

“…developed a heterogeneous catalytic method for the C‐methylation of alcohols, ketones, and indoles with methanol under oxidant‐free conditions by using a Pt‐loaded carbon (Pt/C) catalyst in the presence of sodium hydroxide. This catalytic system is compatible with various substrates to achieve: 1) β‐methylation of primary alcohols; 2) α‐methylation of ketones; and 3) selective C3‐methylation of indoles (Figure ) …”