Quaternary Ammonium Salts as Alkylating Reagents in C–H Activation Chemistry

Abstract

A rhodium(I)-catalyzed alkylation reaction of benzylic amines via C(sp)-H activation using quaternary ammonium salts as alkyl source is described. The reaction proceeds via in situ formation of an olefin via Hofmann elimination, which is the actual alkylating reagent. This represents an operationally simple method for substituting gaseous and liquid olefins with solid quaternary ammonium salts as alkylating reagents, which is transferable to other C-H activation protocols as well.

Rhodium-catalyzed direct alkylation of benzylic amines using alkyl bromides

“…Drying under reduced pressure delivered 3 in 32% (39 mg) yield. TLC: R f  = 0.74 (LP/EtOAc 10:1); analytical data are in accordance to the literature [8]. …”

“…Then, the flash column chromatography was continued using a gradient which varies the solvents from 0% to 5% EtOAc within 1 h. Drying under reduced pressure delivered 8 in 42% (65 mg) yield as yellow oil. TLC: R f  = 0.51 (LP/EtOAc 10:1); analytical data are in accordance to the literature [8]. …”

“…The product was dried under reduced pressure and 6 was isolated in 40% (56 mg) yield as pale yellowish oil. Analytical data are in accordance to the literature [8]. …”

“…The reaction works with slightly lower efficiency as the previously disclosed protocol using quaternary ammonium salts [8]. Linear and unsubstituted alkyl bromides give the best results and examples up to a C22 chain length were reported.…”

“…However, it has to be mentioned that literature examples often limit themselves to functional group-substituted or long-chain alkenes to avoid working with gaseous reagents. We have shown, previously, that gaseous alkenes can be replaced by quaternary ammonium salts, which deliver olefins in-situ via Hofmann elimination (Scheme 1) [8].

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