Lewis Acid‐Catalyzed Yne‐Carbonyl Metathesis of Ynamides and Cyclobutanones: Facile Synthesis of Functionalized Alkylidenecyclobutanes

Abstract

An atom‐economical strategy for the synthesis of functionalized alkylidenecyclobutanes (ACBs) via Lewis acid‐catalyzed yne‐carbonyl metathesis of ynamides and cyclobutanones is described. This strategy features mild reaction conditions, ready availability of starting materials, and broad functional group tolerability. Furthermore, the imide group is easily converted to acid, ester, and amide, thus providing an efficient access to various functionalized ACBs.

Catalytic C–C Cleavage/Alkyne–Carbonyl Metathesis Sequence of Cyclobutanones

“…Introduction of a pendant alkyne would provide an opportunity for a further intramolecular alkyne–carbonyl metathesis sequence using the same catalyst (Scheme , top). Although Lewis acids such as TiCl 4 , EtAlCl 2 , and BF 3 ·Et 2 O, among others, typically in stoichiometric amounts, have been reported to promote ring-opening of 3-donor-substituted cyclobutanones (the “push–pull” structure), such a catalytic ring-opening/alkyne–carbonyl metathesis (ROACM) sequence has never been realized before . Notably, alkyne–carbonyl metathesis (ACM) has emerged as an efficient pathway to α,β-unsaturated compounds .…”

“…Based on the above investigations and literature precedents, − a plausible reaction pathway is proposed in Scheme . The reaction proceeds by Lewis acid activation of the cyclobutanone moiety to furnish cationic intermediate B , which provides Int1 via σ-bond rotation, leaving space for two H 2 O molecules to participate in the concerted deprotonation/protonation process to deliver enone C .…”

Approach to Tertiary-Type β-Hydroxyl Carboxamides Through Sc(OTf)3-Catalyzed Addition of Ynamides and Ketones

“…Our investigation started with the addition reaction of ynamide 1a and ketone 2a. First, similar conditions (TiCl 4 and BF 3 • Et 2 O) used by Matsuo 17 and Xu 15 failed to promote this addition process (Table 1, entries 1−2). Initial trials with Sc(OTf) 3 in several solvents also turned out to be fruitless (Table 1, entries 3−5).…”

“…Recent years, ynamide has undoubtedly become one of the most fascinating building blocks in synthetic chemistry, and many important chemical conversions of ynamides have been successfully achieved . Among them, reactions of ynamides with ketones were reported to afford different products including acrylic amides, γ-hydroxyenamides, and α-halo-γ-hydroxyenamides under the promotion of different Lewis acids (Figure ). As a continuation of our interest in synthetic application of ynamides, we have reported an effective approach to access functionalized pyrido and pyrrolo­[1,2- c ]­[1,3]­oxazin-1-ones through nucleophilic addition–cyclization process of N,O -acetal with ynamides .…”

Zinc-Catalyzed Alkyne–Carbonyl Metathesis of Ynamides with Isatins: Stereoselective Access to Fully Substituted Alkenes

“…Recently, this methodology has attracted the attention of the synthetic community that could serve as an efficient and atom-economic alternative to the Wittig reaction by the straightforward construction of α,β-unsaturated carbonyls. In this context, photoinduced, , Lewis acid- − or Brønsted acid-catalyzed, gold-catalyzed, and other catalytic alkyne–carbonyl metathesis reactions have been reported. Furthermore, these attractive methods have been incorporated and explored in the total synthesis of natural products and complex molecules .…”