Recent Advances in Methylation: A Guide for Selecting Methylation Reagents.

Chen, Yantao

Methylation is a well‐known structural modification in organic and medicinal chemistry. This review summarizes recent advances in methylation by categorizing specific methylation reagents. The challenges of mono N‐methylation of aliphatic amines and N‐methylation of peptides are discussed. This review will be useful for chemists wanting to select the appropriate reagents for methylation chemistry. Based on the large diversity of methylation reagents and their wide scope, this review also broadens perspectives on which strategies to select for utilizing a particular methylation, resulting in an increased flexibility in synthetic route planning. Methylation mine: In this work, 22 different methylation reagents are reviewed, 12 of which are shown in the graphic. MeI, Me3OBF4, and methyl sulfonates are red because of their toxicity or too high electrophilicity. HCHO is blue owing to its over‐methylation in reductive aminations when a primary amine is the substrate, and a secondary amine product is desired. The rest are colored green because of low toxicity (dimethyl carbonate, DMC), low cost (MeOH, CO2, HOAc, FA), or popular application in high‐through‐put screenings (methyl boronic acid, MBA, MeBF3K, trimethylboroxine, TMB).

SULFONATES; METHYLATION

Chemistry - A European Journal, 2019, Vol 25, Issue 14, p3405

0947-6539

Academic Journal

10.1002/chem.201803642