Synthesis of thiazoles by desulfurative cyclization/ring expansion cascade reaction of S-azirinyl xanthates: two mechanistically distinct radical pathways

Abstract

S-Azirinyl xanthates were synthesized as novel 2H-azirine derivatives exhibiting dual reactivity toward free radicals. Carbon-, tin-, and silicon-centered radicals initiate a desulfurization/ring expansion cascade of these compounds to form thiazoles in fair to good yields. Radicals can react with azirinyl xanthates either at the nitrogen (stannyl radicals) or sulfur (alkyl and silyl radicals), transforming them into the thiazoles through the intermediate formation of either aziridinyl or thiaazabicyclopentyl radicals, respectively. Both transformations do not involve the degenerative radical transfer and are unprecedented for the radical chemistry of xanthates.

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Introduction

Xanthate esters have emerged as versatile precursors for carbon-centered radicals in organic synthesis, owing to the ease of introduction of the dithiocarbonate group into a wide range of substrates and the ability of these esters to undergo selective homolytic cleavage at either the C–S or C–O bond. This dual reactivity, combined with diverse radical initiation strategies, offers exceptional synthetic flexibility. Among the most prominent applications is the Barton–McCombie deoxygenation, in which secondary alcohols are reduced to hydrocarbons under mild, radical-mediated conditions via S-methyl xanthates (Scheme 1a).¹ The C–S bond cleavage in O-ethyl xanthates further enables degenerative radical transfer to alkenes, generating functionalized xanthates that serve as versatile precursors for sulfur-containing heterocycles (Scheme 1a).² Beyond small-molecule transformations, xanthates have been widely employed as chain transfer agents in reversible addition–fragmentation chain transfer (RAFT) polymerization.³ Moreover, xanthate-derived radicals can participate in Giese-type alkylation reactions and be efficiently trapped by a variety of radical acceptors,⁴ highlighting their broad applicability in modern radical chemistry.

Scheme 1 Radical reactions of xanthate esters.

Several protocols have been developed for the generation of alkyl radicals from xanthate esters. Traditional radical initiators such as dilauroyl peroxide (DLP) and tributyltin hydride (Bu₃SnH) are commonly employed. More recently, alternative approaches have been reported, including the tetraaryldisilane/AIBN system,^4a photocatalytic conditions,^4b and visible-light irradiation in the presence of xanthate/NHC–borane electron donor–acceptor (EDA) complexes.^4c

Importantly, all of the above processes, including radical rearrangements from O- to S-esters of xanthates,⁵ proceed while preserving the integrity of the dithiocarbonate group. However, some radical reactions of thiocarbonyl-containing substrates, such as thioureas and thiocarbamates with multiple bonds, involve partial transfer of functional-group atoms to the final product.⁶ Within the xanthate series, only a few examples of this type of transformation are known. In particular, Bachi's group reported the Bu₃Sn-radical-induced cyclization of S- and O-homoallyl xanthates to give dihydrothiophen-2-ones or dihydrofuran-2-thiones, respectively (Scheme 1b).⁷ Recently Xing and co-workers synthesized β-S-glycosides from glycosyl xanthates under photocatalytic conditions via generation of glycosylthiyl radicals (Scheme 1c).⁸

In this work, we have synthesized xanthate esters having S-azirinyl substituents, whose unique structure unlocks new modes of reactivity for the dithiocarbonate group. According to the experimental and calculated data presented below, alkyl and stannyl radicals trigger different mechanisms of two-atom expansion of the azirine ring of these compounds involving the dithiocarbonate group. These reactions of azirinyl xanthates with Bu₃SnH or DLP as radical initiators provide a new approach for the synthesis of 2-alkoxythiazole-5-carboxylic esters.

Results and discussion

In our search of new effective synthetic applications of difunctionalized 2H-azirines,^9,10 we became interested in previously unreported azirine-2-carboxylic acid derivatives having an S-xanthyl substituent at C2 as promising building-blocks for heterocyclic synthesis as well as potential precursors of elusive azirin-2-yl radicals. Xanthate esters 3a–s were prepared from 2-bromoazirine-2-carboxylic acid derivatives 1a–l and potassium alkyl xanthates 2a–f (Scheme 2). The reaction proceeded smoothly in acetonitrile at room temperature for 10 min to give the products in yields typically approaching quantitative. The structures of xanthates 3a–s were confirmed by NMR and HRMS data. Specifically, ¹³C NMR spectra display signals at 210 and 44 ppm, corresponding to the carbon of the dithiocarbonate group and the C2 atom of the azirine ring, respectively. Xanthate 3r was unstable on silica gel and was used in further experiments without purification.

Scheme 2 Synthesis of xanthates 3. ^aCrude xanthate 3r was used in the next step without purification.

The structural uniqueness of the synthesized xanthates lies in the presence of three radical-sensitive centers: the sulfur atom of the xanthate moiety, the azirine C3 atom, and the nitrogen atom. Radical addition at the C3 atom of azirine has been described for alkyl radicals generated in the RI/Et₃B/O₂ system.¹¹ We have previously shown that 2-cyclohexylcarbonyl-substituted azirine-2-carboxylic ester 3′ reacts with the tributylstannyl radical generated by heating a Bu₃SnH/ACHN mixture in toluene to form the mixture of 1,3-oxazin-6-one B and oxazole C (Scheme 3).¹² The formation of both products was found to begin with the attack of the stannyl radical on the azirine nitrogen to form aziridinyl radical A. It should be noted that this is one of the extremely rare examples of azaphilic reactivity of stannyl radicals.¹³ With this in mind, we subjected xanthate 3a, having three potential radical-reactive sites, to the same reaction conditions and obtained thiazole 4a in 53% yield as the sole product. The intramolecular two-atom expansion of an azirine ring to a thiazole system is a new reaction in azirine chemistry. Only three examples of intermolecular transformations of azirines to thiazoles are known in the literature, which use isothiocyanates, thioamides, and ammonium thiocyanate as sulfur-containing reaction partners.¹⁴ Thiazoles represent a significant heterocyclic motif found in natural products¹⁵ and serve as valuable scaffolds in drug and agrochemical discovery.¹⁶ Among the plethora of methods for preparing thiazoles,¹⁷ only a few involve a radical cyclization as a key step.¹⁸ The described synthesis of thiazole 4a from azirine 3a may be an example of such a “free radical approach”¹⁹ to thiazole derivatives, which motivated us to optimize its conditions and investigate its mechanism in detail.

Scheme 3 Free-radical reactions of carboxylic ester 3′ and xanthate ester 3a.

The transformation of 3a to 4a did not occur under heating in the absence of free radical sources (Table 1, entry 1). Heating 3a with thiophenol or triethylsilane likewise gave no reaction (entries 2 and 3). No product was formed in the presence of AIBN alone (entry 6), although trace amounts of 4a were observed when Et₃SiH was combined with AIBN (entry 5). In contrast, experiments with ACHN, (BzO)₂, and DLP showed higher yields of the product, which in particular reached 77% when using a 3.5-fold excess of DLP (entries 7–13). It is important to note that to achieve complete conversion of azirine and minimize the consumption of DLP, it should be added gradually, in portions of 0.5 equiv. every 30 min. Bu₃SnH showed comparable efficiency (entries 14 and 15), while the highest yield of the product was obtained in the TTMSS-promoted reaction (entry 16). Notably, the addition of AIBN in these experiments had little effect on the product yield (entries 17–19), which indicates the participation of atmospheric oxygen in the initiation of the radical cascade. This was further confirmed by the reaction of 3a with TTMSS (1.5 equiv.), carried out under an inert atmosphere in toluene freshly distilled from sodium benzophenone ketyl, which gave a significantly lower yield of 4a (entry 20) compared to the same reaction in toluene distilled over sodium (entry 16). Thus, it is advisable to carry out the synthesis of 4a from 3a by heating at 110 °C in non-deoxygenated anhydrous toluene using TTMSS (1.5 equiv.) as a reagent. However, due to the high cost of TTMSS, further experiments were performed using less expensive reagents: Bu₃SnH and DLP, which also showed good results in optimizing the conditions of the model reaction. All synthesized xanthates 3a–s were tested as substrates for the preparation of thiazoles 4 using Bu₃SnH (2 equiv.) as reagent in anhydrous toluene at 110 °C (method A). To compare the efficiency of the reagents, some reactions were carried out in DCE at 84 °C in the presence of DLP (3.5 equiv.) (method B).

Table 1 Optimization of the synthesis of thiazole 4a from azirine 3a

Entry	Reagent,^a equiv.	Solvent	Temperature, °C	Reaction time, h	Yield of 4a, ^b %
a AIBN = 2,2′-azobis(isobutyronitrile); ACHN = 1,1-azobis(cyclohexanecarbonitrile); DLP = dilauroyl peroxide; TTMSS = tris(trimethylsilyl)silane. b Yields were determined by ^1H NMR spectroscopy using CH2Br2 as an internal standard. c DLP was added at 0.5 equiv. every 30 min. d Deoxygenated toluene was used.
1	—	Mesitylene	140	24	0
2	PhSH (1)	Toluene	110	4	0
3	Et3SiH (1)	Toluene	110	4	0
4	PhSH (1), AIBN (0.25)	Toluene	110	7	0
5	Et3SiH (1), AIBN (0.25)	Toluene	110	7	6
6	AIBN (1)	Toluene	110	4	0
7	ACHN (1)	Toluene	110	4	13
8	ACHN (2.1)	Toluene	110	10	18
9	(BzO)2 (1)	Toluene	110	4	33
10	DLP (1)^c	Toluene	110	4	52
11	DLP (1)^c	DCE	84	4	44
12	DLP (2)^c	DCE	84	4	56
13	DLP (3.5)^c	Toluene	110	4	77
14	Bu3SnH (1)	Toluene	110	4	54
15	Bu3SnH (2)	Toluene	110	4	67
16	TTMSS (1.5)	Toluene	110	5	83
17	Bu3SnH (2), AIBN (0.25)	Toluene	110	4	57
18	TTMSS (1), AIBN (0.25)	Toluene	110	4	60
19	TTMSS (1.5), AIBN (0.25)	Toluene	110	4	62
20	TTMSS (1.5)	Toluene^d	110	5	50

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The reaction demonstrated low sensitivity to the nature of the substituent at C3 of the azirine ring (Scheme 4). O-Ethyl-O-isobutyl-, and O-(1R)-menthyl xanthate esters 3a–m,q with para-/meta-substituted aromatic group, 2-thienyl or methyl group at this position reacted smoothly under method A conditions to give thiazoles 4a–m,q in fair to good yields. Less satisfactory results were obtained in the reactions of O-(2,2,2-trifluoro)ethyl, O-benzyl xanthates (compounds 4o,p), allobetulin-based xanthate (compound 4r), and xanthate 4n having ortho-substituted phenyl group in the azirine ring. Xanthate 3p with (morpholin-4-yl)carbonyl moiety at the azirine ring afforded a complex mixture of products under both method A and method B conditions, which proved difficult to separate.

Scheme 4 Synthesis of thiazoles 4. ^aYield of 4r was calculated on 1a.

The transformation of azirinyl xanthates 3 to thiazoles 4 is a multistep process in which the two-atom expansion of the azirine ring occurs via the N–C2 bond cleavage and is accompanied by loss of one sulfur atom. To date, no reactions of xanthate esters with free radicals have been reported to proceed through fragmentation of the dithiocarbonate group and to give a nitrogen heterocycle. The closest analogy of the observed process lies outside the chemistry of organosulfur compounds and is associated with the reactivity of 2-acyloxyazirines toward the Bu₃SnH/radical initiator system (Scheme 3).¹¹ These reactions typically afford 5-hydroxy-1,3-oxazin-6-ones, although in some cases oxazoles are formed through azirine ring expansion across the N–C2 bond with the loss of an oxygen atom. The proposed mechanism of their formation begins with the attack of the tributylstannyl radical on the azirine nitrogen to generate the aziridinyl radical followed by three-membered ring opening. The similarity between Bu₃SnH/ACHN-promoted azirine–oxazole and azirine–thiazole transformations suggests that they may proceed through analogous pathways. However, this analogy becomes less straightforward considering that the transformation of 3 into 4 also occurs under DLP initiation, where addition of an undecyl radical to the azirine nitrogen can be excluded. To clarify the mechanisms of these reactions, DFT calculations (UMPWB1K/cc-pVTZ/LANL2DZ, PCM for toluene, 383 K) were performed for the energy parameters of various pathways for the transformation of model azirine 3t into thiazole 4t. To simplify the calculations, trimethylstannyl and ethyl radicals were used as free radical agents.

Two distinct mechanistic scenarios can be envisioned for the transformation of azirine 3t into thiazole 4t, depending on the nature of the radical initiator. The calculations suggest that for the Me₃Sn radical the most favorable route begins with attack on the azirine nitrogen, affording aziridinyl radical 5 (Fig. 1, route a, black line). This intermediate undergoes sequential ring opening to radical 6, 5-exo-trig cyclization to thiazoline-2-thiyl radical 7, 1,3-stannyl shift to isomer 8, and final β-scission aromatization, producing thiazole 4t. Each step in this sequence has relatively low activation barrier, consistent with the experimental conditions. An alternative thiophilic attack at the thiocarbonyl sulfur via TS6 (Fig. 1, route b, red line) has an energy barrier 1.6 kcal mol⁻¹ lower than TS1, but the energy of TS8 is significantly higher than that of TS1, rendering this branch a reversible dead-end. Radical 9, formed after sulfur attack, may instead dissociate into azirinyl radical 11 and stannylxanthate 12; the former can undergo either degenerative transfer with substrate 3t or hydrogen atom transfer (HAT) with Me₃SnH, accounting for the reduced azirine 13 observed in minor amounts (see the SI, Section S9). Overall, the calculations support the nitrogen-attack sequence (route a) as the operative pathway for trialkylstannane-initiated cyclization. In contrast, more nucleophilic alkyl radicals²⁰ such as Et˙ are unreactive toward azirine nitrogen¹² and exclusively follow the thiophilic route (Fig. 2, black line). In this case, initial sulfur attack generates radical 14, which undergoes 4-exo-trig cyclization to bicyclic radical 15, followed by the aziridine ring opening (TS13) and aromatization (TS14). Importantly, the dissociation of radical 14 into azirinyl radical 11 and xanthate 17 proceeds faster than the cyclization to 15. However, in the absence of a hydrogen donor, radical 11 is capable of reacting only with the C=S-substrates present in the reaction mixture, xanthate 17 and azirine 3t. Its reaction with 3t is a degenerate process that does not lead to new products while its addition to xanthate 17 regenerates radical 14 which then through higher energy transition states (TS12 and TS13) is eventually converted into thiazole 4t.

Fig. 1 Energy profiles (Gibbs free energies, kcal mol⁻¹, DFT UMPWB1K/cc-pvtz/LANL2DZ, PCM for toluene, 383 K) for the reactions of azirine 3t with Me₃Sn-radical.

Fig. 2 Energy profiles (Gibbs free energies, kcal mol⁻¹, DFT UMPWB1K/cc-pvtz/LANL2DZ, PCM for toluene, 383 K) for the reactions of azirine 3t with Et-radical.

Taken together, these results highlight the decisive role of the radical initiator in dictating the pathway of azirine-to-thiazole conversion: trialkylstannyl radicals induce nitrogen-centered initiation, whereas alkyl radicals enforce sulfur-centered attack followed by unique 4-exo-trig cyclization.

In addition to the DFT study, control cross experiments were carried out to clarify whether the C2–S bond of azirines 3 is cleaved during reactions initiated by tributylstannyl and undecyl radicals. The rationale was that if dissociation occurs at this bond, then a mixture of two azirines, differing in both the azirine and xanthate fragments, would generate not only the expected products but also “mixed” thiazoles, containing fragments from different azirines. In the absence of such a cleavage, no mixed thiazoles should be observed. When a 1 : 1 mixture of azirines 3m and 3e was heated with Bu₃SnH in toluene at 110 °C, only thiazoles 4e and 4m were formed, with no trace of “mixed” thiazoles 4c and 4u (Scheme 5). For the peroxide-initiated reaction, a mixture of azirines 3m and 3f was used, which enables to achieve acceptable separation of signals in the ¹H NMR spectrum of the reaction mixture. In the mixture obtained after heating in toluene in the presence of DLP all four possible thiazoles 4m, 4f, 4c, and 4n in 9.6 : 3.8 : 3.6 : 1 ratio were found. The absence of “mixed” thiazoles among the products of the Bu₃SnH-initiated reaction and their formation in the DLP-initiated reaction (thiazoles 4c and 4n) are in good agreement with the results of the DFT calculations and confirm that (a) these reactions proceed via different mechanisms, and (b) the DLP-initiated reaction includes homolytic cleavage at the C_az–S bond. We have previously shown that TTMSS, unlike Bu₃SnH, is inactive toward 2-acyloxyazirines of type 3′ (Scheme 3) even in the presence of AIBN. It follows that the tris(trimethylsilyl)silyl radical generated from it exhibits thiophilic properties and reacts with azirinyl xanthates 3 in the same way as alkyl radicals, namely via path b (Fig. 1).

Scheme 5 Control cross experiments.

Conclusions

In conclusion, S-azirinyl xanthates were prepared in excellent yields from 2-bromoazirine-2-carboxylic acid derivatives and potassium O-alkyl xanthates. These new 2H-azirine derivatives displayed dual reactivity toward free radicals. Carbon-, tin-, and silicon-centered radicals trigger the desulfurative cyclization/ring expansion cascade, converting these compounds into thiazoles in fair to good yields. Azirinyl xanthates react with radicals either at the nitrogen (stannyl radicals) or at the sulfur (alkyl and silyl radicals), transforming into the thiazoles in two different pathways, through the intermediate formation of either aziridinyl or thiaazabicyclopentyl radicals. Both transformations do not involve degenerative radical transfer steps and are unprecedented for the radical chemistry of xanthates.

Author contributions

M. S. N. together with A. V. A. conceived of the project and wrote the manuscript. D. V. S. conducted all experiments and characterized the novel compounds. M. S. N. and A. F. K. performed the DFT calculations, A. V. A. and N. V. R. contributed to the study of reactions mechanisms and editing of the manuscript. All authors contributed to discussions.

Conflicts of interest

There are no conflicts to declare.

Data availability

The data supporting this article have been included as part of the supplementary information (SI). Supplementary information: spectroscopic data for all new compounds and computational details. See DOI: https://doi.org/10.1039/d5qo01233c.

CCDC 2468368 (4a) contains the supplementary crystallographic data for this paper.²¹

Acknowledgements

We gratefully acknowledge the financial support of the Russian Science Foundation grant 23-13-00115. This research used resources of the Magnetic Resonance Research Centre, Chemical Analysis and Materials Research Centre, Computing Centre, and Centre for X-ray Diffraction Studies of the Research Park of St Petersburg State University.

References

1. S. W. McCombie, W. B. Motherwell and M. J. Tozer, The Barton–McCombie reaction, Org. React., 2012, 77, 161–591.
2. B. Quiclet-Sire and S. Z. Zard, The xanthate radical addition route to sulfur heterocycles, ARKIVOC, 2024, 5, 202412199.
3. (a) S. W. McCombie, B. Quiclet-Sire and S. Z. Zard, Reflections on the mechanism of the Barton-McCombie deoxygenation and on its consequences, Tetrahedron, 2018, 74, 4969–4979; (b) L. Allegrezza and D. Konkolewicz, PET-RAFT polymerization: mechanistic perspectives for future materials, ACS Macro Lett., 2021, 10, 433–446.
4. (a) H. Togo, S. Matsubayashi, O. Yamazaki and M. Yokoyama, Deoxygenative functionalization of hydroxy groups via xanthates with tetraphenyldisilane, J. Org. Chem., 2000, 65, 2816–2819; (b) P. López-Mendoza and L. D. Miranda, Photocatalytic xanthate-based radical addition/cyclization reaction sequence toward 2-biphenyl isocyanides: synthesis of 6-alkylated phenanthridines, Org. Biomol. Chem., 2020, 18, 3487–3941; (c) Y. Liu, Q. Zhang, Z. Yu, Y. Tu, Z. Wang, Q. Zhang and L. Wang, Visible-light-mediated metal/base-free stereoselective C-alkyl glycosylation via EDA complexes of glycosyl xanthates and NHC borane, Org. Lett., 2025, 27, 3994–3999.
5. B. Quiclet-Sire and S. Z. Zard, A practical modification of the Barton-McCombie reaction and radical O- to S- rearrangement of xanthates, Tetrahedron Lett., 1998, 39, 9435–9438.
6. (a) J. U. Rhee, B. I. Bliss and T. V. RajanBabu, J. Am. Chem. Soc., 2003, 125, 1492–1493; (b) W. Du and D. P. Curran, Synthesis of carbocyclic and heterocyclic fused quinolines by cascade radical annulations of unsaturated N-aryl thiocarbamates, thioamides, and thioureas, Org. Lett., 2003, 5, 1765–1768; (c) A. G. Angoh and D. L. J. Clive, Radical annulation: a method for preparation of carbocycles, J. Chem. Soc., Chem. Commun., 1985, 980–982.
7. (a) M. D. Bachi and E. Bosch, On the mechanism of reductive degradation of dithiocarbonates by tributylstannane, J. Chem. Soc., Perkin Trans. 1, 1988, 1517–1519; (b) M. D. Bachi, E. Bosch, D. Denenmark and D. Girsh, Tributylstannane-mediated cyclization of thionocarboxylic acid derivatives, J. Org. Chem., 1992, 57, 6803–6810.
8. J.-M. Chen, J.-D. Zhang, J.-C. Wu, J.-Q. Jiang, Z.-K. Fu, X. Li, G.-J. Liu and G.-W. Xing, Switchable photocatalytic stereoselective synthesis of C- and S-glycosides with ethyl xanthate donors, Org. Lett., 2025, 27, 7389–7394.
9. (a) A. V. Agafonova, A. F. Khlebnikov and M. S. Novikov, Synthesis of 4-pyrrolin-3-ones via the 5-endo-trig cyclization of conjugated 2-azaallyl radicals, Org. Lett., 2025, 27, 8229–8233; (b) A. V. Agafonova, M. S. Novikov and A. F. Khlebnikov, Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives, Beilstein J. Org. Chem., 2024, 20, 3191–3197; (c) J. I. Pavlenko, A. V. Agafonova, P. A. Sakharov, I. A. Smetanin, A. F. Khlebnikov, M. A. Kryukova and M. S. Novikov, Stable 2-azaallyl salts as a bridge between 2H-azirines and densely functionalized 2H-pyrroles, J. Org. Chem., 2024, 89, 6281–6291; (d) A. A. Golubev, I. V. Simdianov, I. A. Smetanin, A. V. Agafonova, N. V. Rostovskii, A. F. Khlebnikov and M. S. Novikov, 2-Azidoazirines suitable for click chemistry: synthesis of 1-(2H-azirin-2-yl)-1H-1,2,3-triazoles, New J. Chem., 2024, 48, 19957–19962.
10. For recent reviews on azirine chemistry, see: (a) F. Xu, F.-W. Zeng, W.-J. Luo, S.-Y. Zhang, J.-Q. Huo and Y.-P. Li, 2H-Azirines: recent progress in synthesis and applications, Eur. J. Org. Chem., 2024, 27, e202301292; (b) V. N. Charushin, E. V. Verbitskiy, O. N. Chupakhin, D. V. Vorobyeva, P. S. Gribanov, S. N. Osipov, A. V. Ivanov, S. V. Martynovskay, E. F. Sagitova, V. D. Dyachenko, I. V. Dyachenko, S. G. Krivokolysko, V. V. Dotsenko, A. V. Aksenov, D. A. Aksenov, N. A. Aksenov, A. A. Larin, L. L. Fershtat, V. M. Muzalevskiy, V. G. Nenajdenko, A. V. Gulevskaya, A. F. Pozharskii, E. A. Filatova, K. V. Belyaeva, B. A. Trofimov, I. A. Balova, N. A. Danilkina, A. I. Govdi, A. S. Tikhomirov, A. E. Shchekotikhin, M. S. Novikov, N. V. Rostovskii, A. F. Khlebnikov, Y. N. Klimochkin, M. V. Leonova, I. M. Tkachenko, V. A. Mamedov, V. L. Mamedova, N. A. Zhukova, V. E. Semenov, O. G. Sinyashin, O. V. Borshchev, Y. N. Luponosov, S. A. Ponomarenko, A. S. Fisyuk, A. S. Kostyuchenko, V. G. Ilkin, T. V. Beryozkina, V. A. Bakulev, A. S. Gazizov, A. A. Zagidullin, A. A. Karasik, M. E. Kukushkin, E. K. Beloglazkina, N. E. Golantsov, A. A. Festa, L. G. Voskresensky, V. S. Moshkin, E. M. Buev, V. Y. Sosnovskikh, I. A. Mironova, P. S. Postnikov, V. V. Zhdankin, M. S. Yusubov, I. A. Yaremenko, V. A. Vil’, I. B. Krylov, A. O. Terent'ev, Y. G. Gorbunova, A. G. Martynov, A. Y. Tsivadze, P. A. Stuzhin, S. S. Ivanova, O. I. Koifman, O. N. Burov, M. E. Kletskii, S. V. Kurbatov, O. I. Yarovaya, K. P. Volcho, N. F. Salakhutdinov, M. A. Panova, Y. V. Burgart, V. I. Saloutin, A. R. Sitdikova, E. S. Shchegravina and A. Y. Fedorov, Russ. Chem. Rev., 2024, 93, RCR5125; (c) A. De and A. Majee, Synthesis of various functionalized 2H-azirines: an updated library, J. Heterocycl. Chem., 2022, 59, 422–448.
11. (a) E. Risberg, A. Fischer and P. Somfai, Lewis acid-catalyzed asymmetric radical additions of trialkylboranes to (1R,2S,5R,)-2-(1-methyl-1-phenylethyl)-5-methylcyclohexyl-2H-azirine-3-carboxylate, Tetrahedron, 2005, 61, 8443–8450; (b) E. Risberg, A. Fischer and P. Somfai, Asymmetric radical additions of trialkylboranes to 2H-azirine-3-carboxylates, Chem. Commun., 2004, 2088–2089; (c) M. J. Alves, G. Fortes, E. Guimarães and A. Lemos, Intermolecular alkyl radical addition to methyl 2-(2,6-dichlorophenyl)-2H-azirine-3-carboxylate, Synlett, 2003, 1403–1406.
12. A. V. Agafonova, P. A. Sakharov, I. A. Smetanin, N. V. Rostovskii, A. F. Khlebnikov and M. S. Novikov, Stannyl radical-mediated synthesis of 6H-1,3-oxazin-6-ones from 2-acyloxyazirines or whether free radicals can open the azirine ring?, Org. Chem. Front., 2022, 9, 4118–4127.
13. L. El Kaim and C. Meyer, An unprecedented radical reaction of benzotriazole derivatives. A new efficient method for the generation of iminyl radicals, J. Org. Chem., 1996, 61, 1556–1557.
14. (a) M. Wang, J. Ma, H. Wang, F. Hu, B. Sun, T. Tan, M. Li and G. Huang, Brønsted acid-promoted ring-opening and annulation of thioamides and 2H-azirines to synthesize 2,4,5-trisubstituted thiazoles, Org. Biomol. Chem., 2023, 21, 5532–5536; (b) W.-L. Lei, T. Wang, K.-W. Feng, L.-Z. Wu and Q. Liu, Visible-light-driven synthesis of 4-alkyl/aryl-2-aminothiazoles promoted by in situ generated copper photocatalyst, ACS Catal., 2017, 7, 7941–7945; (c) M. Li, W. Cheng, H. Tang, Y. Wang, Q. Yu, Q. Wang, W. Tang and W. Yi, Cascade reaction of 2H-azirines and o-bromoaryl isothiocyanates: an access to benzo[d]imidazo[2,1-b]thiazoles, J. Org. Chem., 2025, 90(27), 9576–9586.
15. Z. Jin, Imidazole, oxazole and thiazole alkaloids, Nat. Prod. Rep., 2006, 23, 464–496.
16. (a) J. Shearer, J. L. Castro, A. D. G. Lawson, M. MacCoss and R. D. Taylor, Rings in clinical trials and drugs: present and future, J. Med. Chem., 2022, 65, 8699–8712; (b) S. Nadeem, M. F. Arshad, A. Waquar and M. S. Alam, Thiazoles: a valuable insight into the recent advances and biological activities, Int. J. Pharm. Sci. Drug Res., 2009, 1, 136–143; (c) M. F. Arshad, A. Alam, A. A. Alshammari, M. B. Alhazza, I. M. Alzimam, M. A. Alam, G. Mustafa, M. S. Ansari, A. M. Alotaibi, A. A. Alotaibi, A. A. Alotaibi, S. Kumar, S. M. B. Asdaq, M. Imran, P. K. Deb, K. N. Venugopala and S. Jomah, Thiazole: a versatile standalone moiety contributing to the development of various drugs and biologically active agents, Molecules, 2022, 27, 3994; (d) A. Petrou, M. Fesatidou and A. Geronikaki, Thiazole Ring – a biologically active scaffold, Molecules, 2021, 26, 3166.
17. For recent reviews on thiazole synthesis, see: (a) N. Ramyashree, S. L. Kumar, S. Tabassum, S. J. Chundattu and S. Govindaraju, Efficient single-pot synthesis of thiazole derivatives: a synoptic view, ChemistrySelect, 2025, 10, e202404789; (b) G. Kumari, S. Dhillon, P. Rani, M. Chahal, D. K. Aneja and M. Kinger, Development in the synthesis of bioactive thiazole-based heterocyclic hybrids utilizing phenacyl bromide, ACS Omega, 2024, 9, 18709–18746; (c) M. T. Chhabria, S. Patel, P. Modi and P. S. Brahmkshatriya, Thiazole: a Review on chemistry, synthesis and therapeutic importance of its derivatives, Curr. Top. Med. Chem., 2016, 16, 2841–2862.
18. (a) X. Tang, Z. Zhu, C. Qi, W. Wu and H. Jiang, Copper-catalyzed coupling of oxime acetates with isothiocyanates: a strategy for 2-aminothiazoles, Org. Lett., 2016, 18, 180–183; (b) D. Xue, Q. Ge, X. Zhi, S. Song and L. Shao, Metal-free radical cascade cyclization of 2-isocyanoaryl thioethers with alcohols: synthesis of 2-hydroxyalkyl benzothiazoles, Tetrahedron, 2022, 121, 132927; (c) N. Yadav, S. R. Bhatta and J. N. Moorthy, Visible light-induced decomposition of acyl peroxides using isocyanides: synthesis of heteroarenes by radical cascade cyclization, J. Org. Chem., 2023, 88, 5431–5439; (d) K. Luo, W.-C. Yang, K. Wei, Y. Liu, J.-K. Wang and L. Wu, Di-tert-butyl peroxide-mediated radical C(sp²/sp³)−S bond cleavage and group-transfer cyclization, Org. Lett., 2019, 21, 7851–7856.
19. J. Liao, X. Yang, L. Ouyang, Y. Lai, J. Huang and R. Luo, Recent advances in cascade radical cyclization of radical acceptors for the synthesis of carbo- and heterocycles, Org. Chem. Front., 2021, 8, 1345–1363.
20. J. J. A. Garwood, A. D. Chen and D. A. Nagib, Radical polarity, J. Am. Chem. Soc., 2024, 146, 28034–28059.
21. CCDC 2468368: Experimental Crystal Structure Determination, 2025,  DOI:10.5517/ccdc.csd.cc2nvjsv.

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