**1. Introduction**

Ethynylpyrroles are valuable building blocks in the synthesis of many natural and synthetic biologically active compounds, such as antibiotic roseophilin, a potent cytotoxic agent against K562 human erythroid leukemia cells [1] and alkaloid quinolactacide with insecticidal activity [2]. They are applied in the syntheses of inhibitors of EGFR tyrosine kinase, an important target for anticancer drug design [3], the HMG-CoA reductase inhibitors for the treatment of hypercholesterolemia, hyperlipoproteinemia, hyperlipidemia and atherosclerosis [4], selective dopamine D4 receptor ligands [5] and foldamers, synthetic receptors, modified for encapsulation of dihydrogenphosphate ions [6]. Pyrroles with terminal acetylenic substituents take part in the syntheses of both lipophilic and highly hydrophilic BODIPY dyes, which fluoresce with high quantum yields and have low cytotoxicity, which makes it possible to visualize cells [7].

These pyrroles are employed in the development of advanced materials capable of detecting various organic and inorganic targets, such as tetrahedral oxoanions (H2PO4 − and SO4 <sup>2</sup>−) [8] and pyrophosphate anions [9].

Also, high-tech materials, including ultrasensitive fluorescent probes for glucopyranoside [10], photoswitchable materials [11–13], components of dye-sensitized solar cells [14], monomers for organic thin-film transistors [15], prospective for energy storage devices, electrochemically active photoluminescence films are based on terminal ethynylpyrroles [16].

In light of the previous, it is clear that the improvement of the synthesis of ethynylpyrroles is a challenge. Indeed, the approaches to the preparation of these functionalized pyrroles are

**Citation:** Tomilin, D.N.; Sobenina, L.N.; Belogolova, A.M.; Trofimov, A.B.; Ushakov, I.A.; Trofimov, B.A. Unexpected Decarbonylation of Acylethynylpyrroles under the Action of Cyanomethyl Carbanion: A Robust Access to Ethynylpyrroles. *Molecules* **2023**, *28*, 1389. https:// doi.org/10.3390/molecules28031389

Academic Editor: Andrea Penoni

Received: 13 December 2022 Revised: 25 January 2023 Accepted: 26 January 2023 Published: 1 February 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

mainly limited to the deprotection of substituted at the triple bond (usually with TMS/TIPS groups) ethynylpyrroles, the products of the reaction of halopyrroles with the corresponding terminal acetylenes (Sonogashira cross-coupling) [2,5,6,8,17–19]. However, in this case, this coupling has limitations, since many halogenated pyrroles, except for representatives with electron-withdrawing substituents, are neither readily available nor stable [20,21]. Variants of the cross-coupling, such as Negishi reaction of halopyrroles with ethynyl magnesium chloride or zinc bromide [22] or cross-coupling of (1-methylpyrrol-2-yl)lithium with fluoroacetylene [23], are used albeit less often. It should be especially emphasized that almost all ethynylpyrroles synthesized by the above methods lack the substituents at carbon atoms in the pyrrole ring, i.e., the assortment of accessible ethynylpyrrole remains small and need to be extended.

Among other methods are Corey–Fuchs reaction of pyrrole-2-carbaldehydes with CBr4 with further conversion of dibromoolefins to ethynylpyrroles under the action of bases [1,3,7,24,25] and flash vacuum pyrolysis (FVP) of cyclic and linear 2-alkenylpyrroles (750 ◦C), limited to a few examples [26–29] due to difficulties in hardware implementation and requirements for substrates. Base-catalyzed elimination of ketones from tertiary acetylenic alcohols (*retro*-Favorsky reaction), affording pyrroles with terminal acetylenic substituents [30], is a rarer approach to such acetylenes because they could decompose or polymerize at high temperatures (up to 180 ◦C) common for the realization of this synthesis.

The formation of ethynylpyrroles as a result of the deacylation of acylethynylpyrroles was mentioned in only a few cases [31,32], and their yield was insignificant (though alkynones without pyrrole substituents in the presence of alkali metal hydroxides undergo hydrolytic cleavage to form terminal acetylenes [33–35]). For instance, when benzoylethynylpyrrole was treated with NaOH in DMSO (45–50 ◦C, 4 h), debenzoylation was detected by 1H NMR in negligible extent [31] and 7-days keeping of trifluroacetyl ethynylpyrrole over Al2O3 led to the ethynylpyrrole in 24% yield [32]. Certainly, these results were not suitable for the preparative synthesis of ethynylpyrroles.

Recently [36], we have disclosed the reaction of acylethynylpyrroles **1** with MeCN and metal lithium affording pyrrolyl-cyanopyridines **2** in up 87% yield (Scheme 1).

**Scheme 1.** Previous work. Reaction of acylethynylpyrroles with Li/MeCN system to give pyrrolylcyanopyridines.

The synthesis was accompanied by the formation of propargyl alcohols **3** (up to 15%) and small amounts of ethynylpyrroles **4** (up to 5%). The propargyl alcohols **3** were proved to be intermediates in the synthesis of both pyridines and ethynylpyrroles.

These results served as a clue to develop a novel synthesis of ethynylpyrroles, provided we could manage to turn the above side process into a major reaction. Our further successful experiments confirmed this assumption. It appeared that if lithium metal is replaced by *t*-BuOK, the reaction is shifted almost completely to the formation of side ethynylpyrroles. The progress of this synthesis optimization is illustrated in Table 1, wherein the most representative results are presented. As a reference compound, 3-(1 benzyl-4,5,6,7-tetrahydro-1*H*-indol-2-yl)-1-(thiophen-2-yl)prop-2-yn-1-one (**1a**), was chosen believing that the optimal conditions, found for this pyrrolyl acetylenic ketone of higher complexity, will also be valid for the simpler congeners.

In this paper, we report the exceptionally mild decarbonylation of acylethynylpyrroles, readily available from the reaction of pyrroles with electrophilic haloacetylenes in the medium of solid oxides and metal salts [32,37–40], under the action of CH2CN− anion generated in situ in the system MeCN/*t*-BuOK.
