Cooperation of Cis Vicinal Acceptors for Donor–Acceptor Cyclopropane Activation: TfOH-Promoted Ring-Opening/Aryl Shift Rearrangement to 3- and 5-Ylidenebutenolides

Abstract

A convenient route to 3- and 5-ylidenebutenolides from readily available cis-2-acylcyclopropane-1-carboxylates is described. Upon exposure to TfOH, synergistic activation of the vicinal acceptors in cis-2-acylcyclopropane-1-carboxylates generates highly strained bicyclic oxocarbenium ion intermediates, which undergo the ring-opening/aryl shift/deprotonation cascade process to form the 3- or 5-ylidenebutenolides depending on the acyl group. On the other hand, the corresponding trans isomers, from which it is difficult to form such oxocarbenium ions, are inactive under the same conditions.

Facile Synthesis of Polysubstituted 2-Pyrones via TfOH-Mediated Ring Expansion of 2-Acylcyclopropane-1-carboxylates

“…2-Methoxyphenyl or 3-bromo-4-methoxyphenyl groups are not electron-rich enough for this transformation, which gave the 3-ylidenebutenolides as reported previously. 6 In addition to the structural confirmation of 8a referring to the literature, 1f the structure of 8n (CCDC No. : 2083287) was further confirmed by single-crystal X-ray crystallography.…”

“…5 Although DACs with two geminal acceptors are more popularly investigated and used in organic synthesis, we recently found that the synergistic activation of the two vicinal acceptors in DACs can also facilitate the ring-opening transformation of the cyclopropane ring. 6 Importantly, a δ-keto ester unit embedded in the DACs with two vicinal acceptors, i.e., the ketone and ester groups, may be converted to the 2-pyrone skeleton if the cyclopropyl C−C bond between them is selectively cleaved (Scheme 1, a). Although selective scission of such cyclopropyl C−C bond substituted by two vicinal acceptors is electronically unfavored, several elegant pioneering works on Figure 1 Selective bioactive molecules with 2-pyrone unit conversions of DACs with two vicinal acceptors to the 2-pyrones derivatives have been documented.…”

“…Unfortunately, Template for SYNTHESIS © Thieme Stuttgart • New York 2021-06-10 page 2 of 11 only 3,6-disubstituted 2-pyrone derivatives are accessible by this method. In our studies on the selective transformations of DACs synthesized by Kukhtin-Ramirez cyclopropanation of activated alkenes, 6,8 we envisaged that a strongly donating aryl groups may replace the amino group in the work of Zhu and Gong to direct the selective cleavage of the desired cyclopropyl C−C bond for the formation of 2-pyrones (Scheme 1, e). Notably, the convenient availability of these tetrasubstituted DACs is more attractive for this transformation.…”

“…Scheme 1 2-Pyrone derivatives from cyclopropanes with two vicinal acceptors At the outset of our studies, p-methoxyphenyl DAC 7a with the benzoyl group residing cis to the ester group was first subjected to the optimal conditions with the use of 3.5 equiv of TfOH in our previous study; 6 and pleasingly, 2-pyrone 8a was isolated in 95% yield (Scheme 2). Consistent to the facile ring-opening reaction of the cyclopropyl ketones activated by electron-rich aromatic rings via the ring-opened 1,3-zwitterionic intermediates, 9 trans-7a with both carbonyls disposed trans to each other underwent the same ring expansion transformation to 8a as well, albeit in a slightly lower yield.…”

“…These results demonstrate that the strongly donating p-methoxyphenyl group predominantly direct the cyclopropane ring-opening over that through synergistic activation of the two vicinal carbonyl groups, which led to the formation of 3-or 5-ylidenebutenolides. 6 Scheme 2 TfOH-promoted ring expansion reactions of 7a,b and trans-7a,b As shown in Figure 2, a series of the pure cis diastereomers of Kukhtin-Ramirez cyclopropanes 7 were then studied to elucidate the substrate scope. While the reaction of 4-chlorophenyl DAC 7c afforded 2-pyrone 8c in a comparable yield to that of 7b, a fairly poor yield (53%) was obtained from that of the 4-bromophenyl one (7d).…”