Investigations of the generality of quaternary ammonium salts as alkylating agents in direct C–H alkylation reactions: solid alternatives for gaseous olefins

Abstract

C-H alkylation reactions using short chain olefins as alkylating agents could be operationally simplified on the lab scale by using quaternary ammonium salts as precursors for these gaseous reagents: Hofmann elimination delivers in situ the desired alkenes with the advantage that the alkene concentration in the liquid phase is high. In case a catalytic system did not tolerate the conditions for Hofmann elimination, a very simple spatial separation of both reactions, Hofmann elimination and direct alkylation, was achieved to circumvent possible side reactions or catalyst deactivation. Additionally, the truly catalytically active species of a rhodium(I) mediated alkylation reaction could be identified by using this approach.Scheme 1 Murai reaction. † Electronic supplementary information (ESI) available: Detailed experimental procedures and copies of spectra. See

Selective α-Methylation of Aryl Ketones Using Quaternary Ammonium Salts as Solid Methylating Agents

“…From previous findings in our group, we established different quaternary ammonium salts as alkylating agents in metal-catalyzed C–H activation reactions. 16 , 17 …”

“…, MeB­(OH) 2 , Me 4 Sn, Me 3 Al, MeMgCl, or Me 2 Zn) are quite challenging to handle, as some are air-sensitive, show low functional group tolerance, or have to be freshly prepared. , These toxicological and safety concerns encouraged us to search for a novel, safe, and easy-to-handle reagent for direct methylation. From previous findings in our group, we established different quaternary ammonium salts as alkylating agents in metal-catalyzed C–H activation reactions. , …”

“…From previous findings in our group, we established different quaternary ammonium salts as alkylating agents in metalcatalyzed C−H activation reactions. 16,17 The predominant role of quaternary ammonium salts in organic reactions is their application as phase transfer catalysts 18 and ionic liquids. 19 However, their use as alkylating agents in general and methylating agents in particular is quite an unexplored field.…”

Allylation of C‐, N‐, and O‐Nucleophiles via a Mechanochemically‐Driven Tsuji–Trost Reaction Suitable for Late‐Stage Modification of Bioactive Molecules

“…Building upon our prior research involving ammonium salts as solid alkylating agents, [16,18] we initiated our current investigation using allyl trimethylammonium chloride as the allylating agent ( II ), paired with 4‐hydroxybiphenyl ( I ) serving as the nucleophile. Based on mechanistic considerations [19] of the catalytic cycle for Tsuji–Trost allylation, where a leaving group elimination prompts the formation of an η 3 π‐allyl‐Pd II complex, we commenced our optimization studies (see Figure 2) by selecting a known and robust catalytic system of [Pd(allyl)Cl] 2 ( cat 1 ) with cheap rac ‐[2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl] ( rac ‐BINAP) ligand ( L1 ) [20] .…”

Photocatalytic deaminative benzylation and alkylation of tetrahydroisoquinolines with N-alkylpyrydinium salts

“…Among the functionalized THIQs, 1-benzyl-substituted analogues were shown to be able to modulate Ca/K channels, and the synthesis of these compounds is therefore of interest [27]. In our continuing quest to develop methods for the introduction of pure hydrocarbon residues avoiding volatile reagents [28,29], our attention was drawn to stable N-alkyl- (2,4,6-triphenyl)pyridinium salts (Katritzky salts) as alkylation reagents in the context of non-directed C-H functionalization. These salts are known since the late 1970s [30], but only in the last few years they have found application in a wide variety of radical processes, initiated by a single-electron reduction of the pyridinium salts, and subsequent generation of alkyl radicals [31][32][33][34].…”