Synthesis of Bench-Stable N-Quaternized Ketene N,O-Acetals and Preliminary Evaluation as Reagents in Organic Synthesis

Abstract

<div>N-Quaternized ketene N,O-acetals are typically an unstable, transient class of compounds most commonly observed as reactive intermediates. In this report, we describe a general approach to a variety of benchstable N-quaternized ketene N,O-acetals via treatment of pyridine or aniline bases with ethoxyacetylene and an appropriate Brønsted or Lewis acid (triflic acid, triflimide, or scandium(III) triflate). The resulting pyridinium and anilinium salts may be used as reagents or synthetic intermediates in multiple reaction types. For example, N-(1-ethoxyvinyl) pyridinium or anilinium salts can thermally release highly reactive O-ethyl ketenium ions that undergo electrophilic aromatic substitution with electron rich arenes. N-(1-ethoxyvinyl)-2-halopyridinium salts can also be utilized in peptide couplings as a derivative of Mukaiyama reagents, or react with alcohol and amines in nucleophilic aromatic substitutions.</div>

Synthesis of 1-(1-Arylvinyl)pyridin-2(1H)-ones from Ketones and 2-Fluoropyridine

“…When a CH2ClCH2Cl solution of 3a, 3g, and 3k and 2-fluoropyridine was stirred at 80 °C for 1 h, followed by treatment with NaOH aq., the desired product was obtained in 1%, 12%, and 0% yield, respectively. Similar to the result of Majireck et al, 23 the reaction of aryl alkynes 1g' and 1k' with TfOH and 2-fluoropyridine did not afford vinyl pyridones effectively. These results suggest that it is not very likely that both vinyl triflates (3) and vinyl cations play major roles as intermediates in this transformation (Scheme 1).…”

“…5). However, this system is limited to alkynes that contain electron-donating groups such as OMe, 22,23 and pyridinium salts were not observed using phenylacetylene (eq. 6).…”