Cobalt‐Catalyzed C(sp²)−H Methylation by using Dicumyl Peroxide as both the Methylating Reagent and Hydrogen Acceptor

Abstract

The first cobalt-catalyzed direct methylation of a C(sp(2) )-H bond using dicumyl peroxide (DCP) as both the methylating reagent and hydrogen acceptor has been established. The reaction proceeded without the use of any additives, and was proven to be applicable to various amides bearing a 2-pyridinylisopropyl (PIP) directing group, providing an efficient access to o-methyl aryl amides with high functional-group tolerance. Preliminary mechanistic studies suggest a radical process would be involved in the catalytic process.

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…In one case, the dicumyl peroxide (DCP) was employed playing the role of both source of the methyl group and hydrogen acceptor via a radical process. 542 In the second case, an oxidative cross dehydrogenative coupling with various alkylated derivatives (alkanes, (thio)ethers and toluene derivatives) was reported (47 examples, up to 85% yield). 543 …”

Nickel‐Catalyzed Ortho C–H Methylation of Aromatic Amides with Di‐tert‐butyl Peroxide as Methylation Reagent

“…On the basis of the above investigations and previous reports,, , [17c], [17d] a plausible mechanism is proposed in Scheme . Initially, the amide‐coordinated Ni(II) intermediate I is generated by the reaction of amide 1a with Ni(OAc) 2 · 4H 2 O.…”

“…However, one major problem in these reactions is that they are needed to be run under air and moisture free conditions. For this reason, other methylation reagents, such as DMSO, peroxide reagents such as dicumyl peroxide (DCP) and tert ‐butyl peracetate, have been applied in transition‐metal‐catalyzed C–H bond methylations. Along this line, Li and Lu group revealed a cobalt‐catalyzed direct methylation of a C(sp 2 )–H bond using DCP as methylation reagent.…”

Direct Functionalization of C−H Bonds by Iron, Nickel, and Cobalt Catalysis

“…The authors′ hypothesis is that the Lewis acidic Al‐species is also coordinated to the cobaltacycle intermediate, which results in significant steric hindrance, in case the ortho position to the directing group is already occupied. An alternative methylation protocol was reported by Li and Liu, who used the recently introduced TAM moiety as directing group and dicumyl peroxide as methylating reagent as well as hydrogen acceptor (not shown) …”

“…An alternative methylation protocol was reported by Li and Liu, who used the recently introduced TAMm oiety as directing group and dicumyl peroxide as methylating reagent as well as hydrogen acceptor (not shown). [106] In contrast, Balaraman and co-workersr eportedb is-alkynylation of the same type of starting materials (148)u sing mainly 1-bromo-2-TIPS (TIPS = triisopropylsilyl) acetylene as coupling partner to give 150 (Scheme 28, right). [107] Naturally,i fo ne ortho positionw as blockedo nly monoalkynylation took place.…”