Premium
Advances in the Synthesis of Methylated Products through Indirect Approaches
Author(s) -
Chen Yantao
Publication year - 2020
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201901240
Subject(s) - chemistry , trifluoroacetic acid , methylation , reagent , combinatorial chemistry , organic chemistry , biochemistry , gene
Methylation is a well‐known structural modification in organic and medicinal chemistry. In addition to using conventional methylation reagents for direct methylation, indirect methylation approaches have been also successfully applied, particularly to tackle the isolation difficulty among the methylated product, the unreacted starting material, and the dimethylated by‐product due to the structural similarities between them. This review summarizes recent advances in the synthesis of methylated products through indirect approaches – transforming functionalized intermediates into the methylated products. The indirect methodologies surveyed in this review are useful for chemists to select appropriate methylation strategies, particularly for the challenging synthesis of methylated products at a large scale in drug discovery. Abbreviations : AIBN: azobisisobutyronitrile; Cbz: carbobenzyloxy; DBU: 1,8‐diazabicyclo[5.4.0]undec‐7‐ene; DIBAL: diisobutylaluminium hydride; FA: formic acid; Fmoc: fluorenylmethyloxycarbonyl; KOTMS: potassium trimethylsilanolate; LAH: lithium aluminium hydride; LiHBEt 3 : lithium triethylborohydride; PC: photocatalyst; PMHS: polymethylhydrosiloxane; PSMS: zinc bis(phenylsulfonylmethanesulfinate); SAM: S ‐adenosylmethionine; SET: single electron transfer; TBAF: tetra‐ n ‐butylammonium fluoride; TBS: tert ‐butyldimethylsilyl; TEA: trimethylamine; TFA: trifluoroacetic acid; TMS: trimethylsilyl; Ts: 4‐toluenesulfonyl.