Synthesis of α‐Aryl Ketones by Harnessing the Non‐Innocence of Toluene and its Derivatives: Enhancing the Acidity of Methyl Arenes by a Brønsted Base and their Mechanistic Aspects

Abstract

Ketones are the key functional group that recurs in chemistry and biology, and accessing them through simple and economic ways is highly desirable. Herein, we report the synthesis of unsymmetrical ketones from abundant toluene and alkyl esters, where volatile alcohols are the sole byproduct. This protocol applies to a repertoire of substrates bearing electron-donating, electron-withdrawing, and neutral substituents. Most importantly, the organometallic ferrocenyl ester underwent aroylation with ease. This method is the first example to furnish diketones from methyl arenes and diesters. Furthermore, cyclic imide was synthesized by this protocol utilizing KN(SiMe 3 ) 2 as a 'nitrogen' source. Density functional theory studies provide insight into deprotonation of toluene by K + -π interaction by increasing its acidity, and this being the rate-determining step.

Electron donor–acceptor complex enabled cascade reaction of unprotectedo-anilide aryl chlorides for heterocycle synthesis

“…1A, left). According to these results and known reports, both in situ generated solvent anions 11 and t BuOK 12 can serve as electron donors (Fig. 1A, right).…”

Masters of Mediation: MN(SiMe3)2 in Functionalization of C(sp3)−H Latent Nucleophiles

“…However, we reported the first synthesis of diketone 16 h from terephthalate methyl ester (Scheme 10c). [42] Interestingly, on applying the same method for synthesis of dialkylated phthalates, we were ended up with phthalimide were KN-(SiMe 3 ) 2 acted as the 'nitrogen' source. We carried out density functional theory to study how the KN(SiMe 3 ) 2 pKa of 26 in THF deprotonates toluene possessing a pKa of ~43 in DMSO.…”

“…Similar kind of observation also experienced by us in the aroylation of toluene. [42] Interestingly, their developed protocol finds application in the ring opening benzylation of benzotriazoles by the extrusion of nitrogen gas. This reaction proceeds in contrast to the earlier reports which generally requires higher temperature and harsh reaction conditions.…”

Solvent-controlled amidation of acid chlorides at room temperature: new route to access aromatic primary amides and imides amenable for late-stage functionalization

“… 34 Recently, we have shown that KN(SiMe 3 ) 2 promotes the acylation of weakly acidic C–H bonds in toluene derivatives. 35 Along these lines, in 1983 Hart and co-workers reported for the first time that [MN(SiMe 3 ) 2 , M = Li, Na and K] acts as a base and nitrogen source in converting aryl aldehydes to aryl amines. Likewise, Fout, Walsh, and Mao used [MN(SiMe 3 ) 2 , M = Li, Na and K] as a nitrogen source for amination reactions ( Scheme 1b ).…”