Methylation of Arenols through Ni‐catalyzed C—O Activation with Methyl Magnesium Bromide

Abstract

Direct alkylation of arenols with alkyl organometallic reagents has never been approached. Herein we reported the first successful example of nickel‐catalyzed methylation of arenols with methyl Grignard reagents to construct C(sp2)‐C(sp3) bond under mild conditions. The transformation was compatible with broad substrate scope of 2‐naphthol derivatives. Benzyl alcohol and biphenols were also suitable substrates for this methylation.

Transformations of Less-Activated Phenols and Phenol Derivatives via C–O Cleavage

“…248 Later, in 2018, the same group disclosed a direct methylation protocol of naphthols and biphenols catalyzed by Ni(COD) 2 with CM-phos as the ligand with methyl Grignard reagent (Scheme 124). 249 2.6.1.2. C−C Bond Formation with Other Organometallic Reagents (Zn, Li, Al, Ln).…”

A late-stage functionalization tool: sulfonyl fluoride mediated deoxymethylation of phenols

“…13 In 2018, Shi's group reported the first example of nickel-catalyzed direct methylation of arenols with methyl Grignard reagents. 14 In recent years, several relevant examples of conversion of phenolic derivatives to the corresponding methyl compounds have been developed. 15 For instance, You's group pioneeringly demonstrated methylation reactions of some inert phenol derivatives (aryl methyl ether and pivalate) with transition metal catalysis.…”

Ni-Catalyzed Deoxygenative Borylation of Phenols Via O-Phenyl-uronium Activation

“…Realizing that phenols are naturally abundant, readily available, nontoxic, and low-cost, chemists have devoted considerable efforts toward the development of metal-catalyzed deoxygenative cross-coupling reactions of phenol derivatives. ,− Consequently, great progress has been made in the development of catalytic methods for the deoxygenative cross-coupling of a variety of phenol derivatives. Nevertheless, there is still great room for developing deoxygenative cross-coupling of phenols.…”

“…The catalytic methods based on a dearomatization-condensation-rearomatization sequence open a new way to achieve the deoxygenative functionalization of phenols but do not serve as an alternative to the C­(sp 2 )-O oxidative addition-based deoxynative cross-coupling of phenols, due to different products being generated from two types of reactions. Two metal-catalyzed methods have been established to enable the free naphthols to undergo deoxygenative cross-coupling reactions with aryl boronic acid nucleophiles or aryl Grignard reagents in the presence of qualitatively similar Lewis-acid additives to nucleophilic coupling partners as the activators for naphthols, but they fail to work for less π-extended phenols. Since the O–H bond in unprotected phenols is more active toward an oxidative addition than its C­(sp 2 )-O bond, the strategy for deoxygenative cross-coupling reactions of phenols must identify suitable additives to remove the acidic proton of phenols and transform phenol into more active phenol derivatives…”