Nickel‐Catalyzed Methylation of Aryl Halides with Deuterated Methyl Iodide

Abstract

A nickel-catalyzed methylation of aryl halides with cheap and readily available CH3 I or CD3 I is described. The reaction is applicable to a wide range of substrates and allows installation of a CD3 group under mild reaction conditions without deuterium scrambling to other carbon atoms. Initial mechanistic studies on the stoichiometric and catalytic reactions of the isolated [(dppp)Ni(C6 H4 -4-CO2 Et)Br] [dppp=1,3-bis(diphenylphosphanyl)propane] suggest that a Ni(0) /Ni(II) catalytic cycle is favored.

Oxygen Activated, Palladium Nanoparticle Catalyzed, Ultrafast Cross‐Coupling of Organolithium Reagents

“…Forfurther applications in isotope labeling, we considered the direct incorporation of the CD 3 moiety into organic compounds.T he use of deuterated MeI is desirable from acost perspective,and its use with arange of electrophiles has recently been shown by Hu and co-workers. [22] As the reported procedure requires al arge excess of costly CD 3 I (3.5 equiv), we anticipated that our method using in situ generated CD 3 Li could provide av iable alternative (Scheme 6). As we had converted MeI into MeLi using nBuLi (see above), and successfully applied it in crosscoupling also with the 11 Canalogue,anidentical experimental setup for CD 3 Iw as used.…”

Oxygen Activated, Palladium Nanoparticle Catalyzed, Ultrafast Cross‐Coupling of Organolithium Reagents

“…For further applications in isotope labeling, we considered the direct incorporation of the CD 3 moiety into organic compounds. The use of deuterated MeI is desirable from a cost perspective, and its use with a range of electrophiles has recently been shown by Hu and co‐workers . As the reported procedure requires a large excess of costly CD 3 I (3.5 equiv), we anticipated that our method using in situ generated CD 3 Li could provide a viable alternative (Scheme ).…”

Recent Advances in Methylation: A Guide for Selecting Methylation Reagents

“…Recently, Liao et al. disclosed a nickel‐catalyzed methylation of aryl halides with the in situ formed complex of MeZnI[NaI] n ( n =0, 1, 2) by mixing MeI and Zn in the presence of NaI . The reaction can be conducted at room temperature, and the yields are up to 99 %.…”

“…Recently,L iao et al disclosed an ickel-catalyzed methylation of aryl halidesw ith the in situ formed complex of MeZnI[NaI] n (n = 0, 1, 2) by mixing MeI and Zn in the presence of NaI. [157] The reactionc an be conducted at room temperature, and the yields are up to 99 %. In addition, this method particularly suits the syntheses of CD 3 -containing products owing to the readily availablea nd cheap CD 3 I ( Ta ble 14).…”