Catalytic Methylation of CH Bonds Using CO₂ and H₂

Abstract

Formation of CÀC bonds from CO 2 is a much sought after reaction in organic synthesis. To date, other than C À H carboxylations using stoichiometric amounts of metals, base, or organometallic reagents, little is known about C À C bond formation. In fact, to the best of our knowledge no catalytic methylation of CÀH bonds using CO 2 and H 2 has been reported. Described herein is the combination of CO 2 and H 2 for efficient methylation of carbon nucleophiles such as indoles, pyrroles, and electron-rich arenes. Comparison experiments which employ paraformaldehyde show similar reactivity for the CO 2 /H 2 system.

Synthesis and larvicidal activity of indole derivatives against Aedes aegypti (Diptera: Culicidae)

“…The Fischer reaction was carried out using compounds B1‐B3, cyclohexanone or 2‐butanone, H 2 SO 4 as catalyst, and water as solvent, and provided the six indole derivatives (C1‐C6) in low to moderate chemical yields (Scheme ). All the compounds were characterized by IR and 1 H and 13 C NMR spectroscopy (Barf et al, ; Katritzky, Rewcastle, & Vazquez de Miguel, ; Li, Yan, Junge, & Beller, ; Xu et al, ; Zhang, Haag, Li, & Knochel, ).…”

Expanding the Ligand Framework Diversity of Carbodicarbenes and Direct Detection of Boron Activation in the Methylation of Amines with CO2

“…[24] Recently,anelegant procedure for the CO 2 -based methylation of N À Hm oieties mediated by ruthenium catalysts has been developed. [25] Shortly thereafter, this proof of principle was successfully adapted for more benign organocatalysts,n amely NHC-and proazaphosphatrane-promoted reductive functionalization of CO 2 for meth- [29] Hydrogen atoms have been omitted for clarity. Figure 2.…”

The Use of Carbon Dioxide (CO2) as a Building Block in Organic Synthesis from an Industrial Perspective

“…Like in the N ‐methylation, CO 2 /H 2 can also be used for the methylation of aromatic compounds to replace MeOH as the CH 3 source. For example, heteroarenes can be methylated on the heteroarene ring by again using a Ru‐triphos catalyst in combination with an acidic co‐catalyst (Scheme ) …”

“…It is also possible to perform the methylation on electron‐rich arenes at temperatures of up to 160 °C (Scheme ) . This approach could be an alternative to the methylation of electron‐rich arenes, like phenol to ortho ‐cresol with MeOH which is carried out at 350–400 °C in the liquid phase, if the reaction could be extended to the less reactive phenol and related substrates.…”