Solvent-free 1,3-dipolar cycloaddition of azomethine imines with terminal alkynes promoted by calcium fluoride under the ball milling condition

Abstract

A convenient and efficient procedure for the synthesis of N,N-bicyclic pyrazolidinone derivatives has been developed via the reaction of azomethine imines with terminal alkynes under the ball milling condition without solvent, which was promoted by calcium fluoride with a catalyst of copper(I) salt. The cyclization reactions exhibited moderate to high yields.

Copper-Catalyzed Azomethine Imine–Alkyne Cycloadditions (CuAIAC)

“…In the absence of firm experimental and theoretical proofs, the generally accepted plausible mechanism is based on the catalytic Cu(I) acetylide as the reactive species, which undergoes cycloaddition, followed by protonation of the cuprated cycloadduct. 22,24,28,29,31,[33][34][35]37,38,42,45,46 This reaction pathway is supported by experiments performed with copper(I) acetylides, deuterated acetylenes, and/or proton sources, such as D 2 O and AcOD. 29,[33][34][35]38 Copper(I) was, either used directly, 29,33 or formed in situ by reduction of Cu(II) 34,35 or by oxidation of Cu(0).…”

“…The reaction was promoted by calcium fluoride with a copper(I) salt as the catalyst to furnish the cycloadducts in moderate to high yields (Scheme 21). 37 In the Cu(0)-catalyzed version of CuAIAC, copper powder has been successfully employed. A library of 16 representative cycloadducts 54 were synthesized in high yields (>90% in most cases) by treatment of dipoles 53 with ynones 7 in dichloromethane.…”

Mechanochemical and sonochemical heterocyclizations

“…The comminution of o-aminophenol with diethyl acetylenedicarboxylate in a planetary ball mill with NaCl alone yielded benzoxazine 10 (yield > 95%) rather than the corresponding N-vinylated product. The synthesis of N,N-bicyclic pyrazolidinone derivatives 13 through the 1,3-dipolar cycloaddition reaction of azomethine imines with terminal alkynes using a vibratory ball mill in the presence of calcium fluoride and copper(I) salt has been described by Chen et al 15 (Scheme 9). In a typical procedure, a mixture of azomethine imine (0.40 mmol), ethyl propiolate (0.40 mmol), CuI (0.04 mmol), and SiO2 (500 mg) was vigorously milled at a rate of 20 Hz at room temperature for 60 min.…”

Mechanochemistry for Organic Chemists: An Update

“…Catalyst recyclability was addressed by the Ranu group, who used copper‐embedded alumina as the catalyst . Another mechanochemical 1,3‐dipolar cycloaddition was reported by Chen and co‐workers, who used Cu I ‐catalyzed coupling to form bicyclic N , N ‐pyrazolo compounds (Figure a).…”

“…(a) Copper‐catalyzed 1,3‐dipolar cycloaddition, reported by the Zhang group . (b) Directing‐group‐assisted regioselective dehydrogenative arylation .…”