N-Heterocyclic Carbene-Catalyzed Cyclotetramerization of Acrylates

Abstract

N-Heterocyclic carbenes (NHCs) were found to catalyze the unprecedented cyclotetramerization of acrylates, producing the trisubstituted cyclopentenones in moderate yields. The proton or deuterium adducts of the deoxy-Breslow intermediate derived from NHC and two molecules of methyl acrylate were obtained. A reaction mechanism involving the new umpolung/cyclization sequence is proposed.

Theoretical study of the mechanism of the N-heterocyclic carbene-catalyzed cyclotetramerization of acrylates

“…These results indicate that the catalysis involves the intermediate 5 stemming from one molecule of NHC and two molecules of MA. Furthermore, the head-to-tail dimer was not detected by GC analysis during the catalytic reaction, indicating that the α-proton of 2 was not transferred [24]. It is worth noticing that these computational calculations are in good agreement with the experimental results obtained by Matsuoka et al [24].…”

“…Furthermore, the head-to-tail dimer was not detected by GC analysis during the catalytic reaction, indicating that the α-proton of 2 was not transferred [24]. It is worth noticing that these computational calculations are in good agreement with the experimental results obtained by Matsuoka et al [24]. Addition of a third MA molecule to the intermediate 5 generates the intermediate 6.…”

“…The higher free energy of activation found in the case of TS3 ' indicates that the α-proton of 2 is not transferred. Experiments conducted in deuterated trifluoric acid (CF 3 CO 2 D) by Matsuoka et al [24] resulted in the formation of a deoxy-Breslow intermediate with the selective deuterium incorporation at the β-carbon and not at the α-carbon of the terminal ester. These results indicate that the catalysis involves the intermediate 5 stemming from one molecule of NHC and two molecules of MA.…”

“…The next step can either involve the zwitterionic intermediate with a proton transfer [17][18][19][20] or a further addition to electrophilic centers [21][22][23]. In 2013, Matsuoka et al [24] studied the NHC-catalyzed cyclotetramerization of acrylates leading to trisubstituted cyclopentenones under mild conditions (Fig. 1).…”

“…It is believed that the transformation likely proceeds via the formation of a key deoxy-Breslow intermediate and that the mechanism involves the new umpolung/cyclization sequence as depicted in Fig. 2 [24]. We therefore present a detailed density functional theory (DFT) computational investigation of the mechanism of the NHC-catalyzed cyclotetramerization of acrylates.…”