Selective Methylation of Amines with Carbon Dioxide and H₂

Abstract

Put a label on it: Carbon dioxide with H2 is shown to be an efficient and selective methylation reagent for aromatic and aliphatic amines (see scheme; acac=acetylacetonate, triphos = 1,1,1‐tris(diphenylphosphanylmethyl)ethane). A variety of functionalized amines including 13C‐labelled drugs were obtained with good yields and functional‐group tolerance.

Efficient Ruthenium-Catalyzed N-Methylation of Amines Using Methanol

“…Recently, utilization of CO 2 11 as a C-1 source in the presence of silanes 12 or boranes 13 was reported as a promising alternative methylation strategy. A requirement of excess reducing agents, separation of the silyl and borane byproducts and their regeneration, as well as tolerance to reducible functional groups 14 could be, in general, a potential concern in creating multifunctional scaffolds and for large-scale applications. Accordingly, a new protocol was developed to use hydrogen as a reducing agent.…”

Novel type of plasmin inhibitors: Providing insight into P4 moiety and alternative scaffold to pyrrolopyrimidine

“…Alkylation to methyl 4-amino-3-(methylamino)benzoate 20 and methyl 3-amino-4-(methylamino)benzoate 21 was carried out by using 2-chloroacetyl chloride, followed by cyclization using SOCl 2 to give 10 and 11, respectively.…”

Hydrogen

“…In a related reaction, direct methylation of amines has been achieved using CO 2 and hydrogen. 81,82 This approach allowed selective monomethylation of diamines and also the formation of 13 C methylated amines using 13 …”