Photo-induced spirocyclization of biaryl ynones with ammonium thiocyanate: access to thiocyanate-featured spiro[5,5]trienones

Abstract

Photo-promoted mild tandem 6-exo-trig spirocyclization of biaryl ynones with ammonium thiocyanate has been developed to access thiocyanate-containing spiro[5,5]trienones with good yields and regioselectivity. Meanwhile, other thiocyanate-substituted cycles also could be produced under similar conditions. The merits and reaction process of this radical system were examined by a variety of scaled-up operations, functional group transformations, intermediate capture study, and on/off light experiments.

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Organic thiocyanates commonly exhibit important and wide-ranging biological activities and drug properties (Fig. 1).¹ They also can be used as organic scaffolds to produce a variety of thiols,² thioethers,³ thiocarbamates,⁴ and alkynyl thioethers,⁵etc., in synthetic chemistry. To date, various efficient protocols for the construction of aryl, alkyl, or vinyl thiocyanates have been developed by many chemists.^6–9 Among them, as valuable organic substrates, vinyl thiocyanates are commonly produced from alkenes, alkynes, or their derivatives via coupling/addition/cascade reactions (Scheme 1a).^8,9 Recently, our group reported a photo-promoted tandem cyclization of ammonium thiocyanate (NH₄SCN) with aryl acetylenes to access seven-membered exocyclic vinyl thiocyanates (Scheme 1b).¹⁰ Despite this advanced work, diverse mild strategies for the synthesis of spirocycle-containing vinyl thiocyanates with good regioselectivity/yields are still rarely reported (Scheme 1c).

Fig. 1 Representative bioactive thiocyanates and derivative drugs.

Scheme 1 Methods of preparation of vinyl thiocyanates.

On the other hand, spirocycles, representing an important and prevalent organic skeleton, are extensively found in natural products, pharmaceuticals, agrochemicals, as well as in organic chemistry (such as the ligands utilized in metal-catalyzed systems).¹¹ Given that, many efficient protocols for the synthesis of spirocycles have been developed, which involve a variety of transition-metal-promoted dearomatization, nucleophilic/electrophilic dearomatization, oxidative dearomatization, or radical-induced dearomatization processes.^12–15 Among them, diverse spiro compounds were obtained via the radical tandem 5-exo-trig or 6-exo-trig spirocyclization of alkynes with common radical species.^{15c–e,16,17} For instance, efficient cascade 6-exo-trig spirocyclization of biaryl ynones to access spiro[5,5]trienones has been developed by Zhang/Ackermann, Wang, Zhou, Duan, Zhu, Reddy, Perin, Liu, and other groups recently.^16c,g,18 Despite these critical achievements, some challenges still need to be solved by using biaryl ynones as starting materials: (1) more mild and simple reaction conditions need to be found; (2) regioselectivity for the 5-exo-trig, 6-exo-trig, or 7-exo-trig reaction process needs to be controlled; (3) a broader substrate scope and more radical species need to be explored. The above problems are being studied by our group. Based on our previous radical study,¹⁹ we finally developed a mild, solely 6-exo-trig spirocyclization of biaryl ynones with NH₄SCN, which resulted in SCN-modified spiro[5,5]trienones with good regioselectivity and a broad substrate scope. Meanwhile, other SCN-substituted cycles also could be obtained under similar radical conditions.

Initially, 1-(4′-methoxy-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-one and NH₄SCN were selected as model substrates to screen the reaction conditions, and the results are described in Table 1. First, a variety of photocatalysts were tested in this spirocyclization reaction, which indicated that fluorescein was better than rhodamine 6G, rhodamine B, eosin Y, and 4C_ZIPN (entries 1–8). Next, varying the kinds and equivalents of bases resulted in worse outcomes (entries 9–13). Meanwhile, the yield of product 1 was not improved after further optimizations of thiocyanates and the reaction solvent (entries 14–21). Finally, product 1 was gained in 74% yield under the following optimum conditions: 1-(4′-methoxy-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-one (1 equiv., 0.1 mmol), NH₄SCN (3 equiv., 0.3 mmol), fluorescein (0.05 equiv., 0.005 mmol), DMAP (0.2 equiv., 0.02 mmol), CH₃CN (3.5 mL), 18 W blue LEDs, rt.

Table 1 Optimization of reaction conditions^a

Entry	Photocatalyst (mol %)	Thiocyanate (equiv.)	Base (equiv.)	Solvent (mL)	Yield^b (%)
a Reaction conditions: 1-(4′-methoxy-[1,1′-biphenyl]-2-yl)-3-phenylprop-2-yn-1-one (1 equiv., 0.1 mmol), NH4SCN (3 equiv., 0.3 mmol), fluorescein (0.05 equiv., 0.005 mmol), DMAP (0.2 equiv., 0.02 mmol), CH3CN (3.5 mL), 18 W blue LEDs, rt. b Isolated yields.
1	Rhodamine 6G (1)	NH4SCN (3)	DMAP (0.2)	CH3CN (3.5)	59
2	Rhodamine B (1)	NH4SCN (3)	DMAP (0.2)	CH3CN (3.5)	34
3	Eosin Y (1)	NH4SCN (3)	DMAP (0.2)	CH3CN (3.5)	62
4	4CZIPN (1)	NH4SCN (3)	DMAP (0.2)	CH3CN (3.5)	46
5	Fluorescein (1)	NH4SCN (3)	DMAP (0.2)	CH3CN (3.5)	66
6	Fluorescein (2)	NH4SCN (3)	DMAP (0.2)	CH3CN (3.5)	68
7	Fluorescein (3)	NH4SCN (3)	DMAP (0.2)	CH3CN (3.5)	68
8	Fluorescein (5)	NH 4 SCN (3)	DMAP (0.2)	CH 3 CN (3.5)	74
9	Fluorescein (5)	NH4SCN (3)	––	CH3CN (3.5)	70
10	Fluorescein (5)	NH4SCN (3)	DMAP (0.1)	CH3CN (3.5)	72
11	Fluorescein (5)	NH4SCN (3)	DMAP (0.3)	CH3CN (3.5)	62
12	Fluorescein (5)	NH4SCN (3)	Et3N (0.2)	CH3CN (3.5)	69
13	Fluorescein (5)	NH4SCN (3)	K2HPO4 (0.2)	CH3CN (3.5)	60
14	Fluorescein (5)	NH4SCN (2)	DMAP (0.2)	CH3CN (3.5)	59
15	Fluorescein (5)	NH4SCN (4)	DMAP (0.2)	CH3CN (3.5)	51
16	Fluorescein (5)	NaSCN (3)	DMAP (0.2)	CH3CN (3.5)	70
17	Fluorescein (5)	KSCN (3)	DMAP (0.2)	CH3CN (3.5)	64
18	Fluorescein (5)	NH4SCN (3)	DMAP (0.2)	CH3CN (2.5)	38
19	Fluorescein (5)	NH4SCN (3)	DMAP (0.2)	CH3CN (4.5)	48
20	Fluorescein (5)	NH4SCN (3)	DMAP (0.2)	CH3OH (3.5)	66
21	Fluorescein (5)	NH4SCN (3)	DMAP (0.2)	DCE(3.5)	72

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Next, under the optimum conditions, the substrate scope of the spirocyclization reactions was studied as depicted in Table 2. First, the R group on the alkyne moiety of the substrates modified with electron-donating or electron-withdrawing substituents could react well with NH₄SCN in the reaction system, which produced the corresponding SCN-containing spiro[5,5]trienones in 53–88% yields (1–7). In addition, the R group of biaryl ynones bearing halogen, heterocycle, and alkyl groups also were compatible with this radical system, and products 8–13 were isolated in 58–72% yields, respectively. Subsequently, various substituents (such as Me, NO₂, F, and Cl) modifying the aromatic rings adjacent to the ketones of the starting materials afforded the desired products 14–17 in moderate to good yields. Finally, naphthyl and thiophenyl group-containing biaryl ynones also could smoothly proceed with the radical spirocyclization reaction (18–19).

Table 2 Substrate scope of biaryl ynones^a

a Reaction conditions: biaryl ynones (1 equiv., 0.1 mmol), NH₄SCN (3 equiv., 0.3 mmol), fluorescein (0.05 equiv., 0.005 mmol), DMAP (0.2 equiv., 0.02 mmol), CH₃CN (3.5 mL), 18 W blue LEDs, rt, isolated yields.

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Afterward, the functional group tolerance of the dearomative aryl rings of the substrates also was explored under typical conditions (Table 3). First, the dearomative aryl ring-bearing unit with the combination of 3-Me/4-MeO, 3,5-di-Me/4-MeO, 2,4-di-MeO, 3,4-di-MeO, and even 2,3,4-tri-MeO groups all could well undergo the 6-exo-trig spirocyclization process, which gave the corresponding final products in 52–84% yields (20–24). Meanwhile, halogen-modified substrates (such as 2-F/4-MeO, 3-F/4-MeO, and 3-Cl/4-MeO groups) resulted in products 25–27 in 52–75% yields. Notably, the OH or CHO group-containing biaryl ynones also could exist well in this radical system (28–29).

Table 3 Substrate scope of dearomative aryl rings^a

a Reaction conditions: biaryl ynones (1 equiv., 0.1 mmol), NH₄SCN (3 equiv., 0.3 mmol), fluorescein (0.05 equiv., 0.005 mmol), DMAP (0.2 equiv., 0.02 mmol), CH₃CN (3.5 mL), 18 W blue LEDs, rt, isolated yields.

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A variety of application research methods were performed to test the merit and synthetic value of the reaction system (Scheme 2). First, no p-MeO-containing dearomative aryl ring moiety of the substrates could also undergo spirocyclization reaction with good regioselectivity (Scheme 2a and b). Next, product 1 was isolated in a 53% yield with the reaction scaled up to 1 mmol (Scheme 2c). Meanwhile, other unsaturated alkenes or alkynes also were compatible with this radical system, which produced SCN-substituted 5- or 6-membered cycles in moderate yields (Scheme 2d–f). Finally, two functional group transformations have been operated to access the corresponding derivatives 36–37 in 69–75% yields (Scheme 2g and h).

Scheme 2 Scaled-up experiments and further transformations.

Various mechanistic studies were operated to verify the radical process (Scheme 3). First, with the addition of 2,6-di-tert-butyl-4-methylphenol (BHT) or 2,2,6,6-tetramethyl-1-piperidyloxy (TEMPO) into the reaction system, respectively, product 1 was not found by TLC. Excitingly, radical intermediates 38, 39, 40, and 41 all could successfully be detected by HRMS (Scheme 3a and b, also see ESI for details†). The yield of product 1 was very poor under the N₂ atmosphere, which indicated that dioxygen was important for the reaction system (Scheme 3c). Finally, to test the importance of blue light, a variety of on/off light experiments were performed under typical conditions (Scheme 4).

Scheme 3 Mechanistic study.

Scheme 4 On/off light experiments of product 1.

According to the experimental results as well as previous studies,²⁰ a plausible reaction pathway was described as shown in Scheme 5. First, with the assistance of fluorescein/blue light/oxygen, NH₄SCN could smoothly produce the SCN radical. With the formation of the SCN radical, DMAP could stabilize the ammonium ion. Next, vinyl radical A was gained via the SCN radical attacking the triple bond of biaryl ynones, which then underwent spirocyclization and resulted in radical B. Finally, intermediate B proceeded with β-fragmentation to access the final product and methyl radical, which was successfully captured by TEMPO.

Scheme 5 Plausible mechanism.

Conclusions

In conclusion, a mild and available radical spirocyclization of NH₄SCN with biaryl ynones was accomplished, which could efficiently produce various SCN-modified spiro[5,5]trienones. Other unsaturated substrates also were compatible with this reaction system to access SCN-containing cycles. This radical system gave a good green matrix (such as atom economy and E-factor, respectively calculated as 91% and 64%).²¹ Meanwhile, a variety of applied research and mechanistic studies were also completed in this work. Additional studies on the construction of other spirocycles or fused cycles are ongoing in our laboratory.

Author contributions

S. Chen and Q. Yan studied the reaction conditions, substrate scopes, further transformations, and plausible mechanisms. J. Fan and C. Guo prepared a variety of biaryl ynones. Finally, L.-J. L., Z.-Q. Liu, and Z.-J. Li all conducted the corresponding experiments and wrote the manuscript.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

This project is supported by the National Natural Science Foundation of China (21702044, 21971116), the Natural Science Foundation of Hebei Province (B2020201014, B2022201059), Science and Technology Project of Hebei Education Department (QN2019063), and Research Innovation Team of College of Chemistry and Environmental Science of Hebei University (hxkytd-py2102).

References

1. For representative references, see: (a) A. K. Mukerjee and R. Ashare, Isothiocyanates in the chemistry of heterocycles, Chem. Rev., 1991, 91, 1–24; (b) R. J. Lukens, Chemistry of Fungicidal Action, Chapman and Hall, London, 1971; (c) Y. Yasman, R. A. Edrada, V. Wray and P. Proksch, New 9-Thiocyanatopupukeanane Sesquiterpenes from the Nudibranch Phyllidia varicosa and Its Sponge-Prey Axinyssa aculeata, J. Nat. Prod., 2003, 66, 1512–1514; (d) J. R. Falck, S. H. Gao, R. N. Prasad and S. R. Koduru, Electrophilic α-thiocyanation of chiral and achiral N-acyl imides. A convenient route to 5-substituted and 5,5-disubstituted 2,4-thiazolidinediones, Bioorg. Med. Chem. Lett., 2008, 18, 1768–1771; (e) E. Elhalem, B. N. Bailey, R. Docampo, I. Ujvary, S. H. Szajnman and J. B. Rodriguez, Design, Synthesis, and Biological Evaluation of Aryloxyethyl Thiocyanate Derivatives against Trypanosoma cruzi, J. Med. Chem., 2002, 45, 3984–3999; (f) V. A. Kokorekin, A. O. Terent'ev, G. V. Ramenskaya, N. E. Grammatikova, G. M. Rodionova and A. I. Ilovaiskii, Synthesis and Antifungal Activity of Arylthiocyanates, Pharm. Chem. J., 2013, 47, 422–425; (g) Z. An, Y. Liu, P. Zhao and R. L. Yan, I₂-Promoted [3 + 2] Cyclization of 1,3-Diketones with Potassium Thiocyanate: a Route to Thiazol-2(3H)-One Derivatives, Adv. Synth. Catal., 2021, 363, 3240–3244; (h) K. M. Werner and J. M. de los Santos, Weinreb SM, Shang MY. A Convergent Stereoselective Synthesis of the Putative Structure of the Marine Alkaloid Lepadiformine via an Intramolecular Nitrone/1,3-Diene Dipolar Cycloaddition, J. Org. Chem., 1999, 64, 686–687; (i) R. P. Austin, P. Barton, R. V. Bonnert, R. C. Brown, P. A. Cage, D. R. Cheshire, A. M. Davis, I. G. Dougall, F. Ince and G. Pairaudeau, QSAR and the Rational Design of Long-Acting Dual D₂-Receptor/β₂-Adrenoceptor Agonists, J. Med. Chem., 2003, 46, 3210–3220; (j) S. P. Tanis, T. T. Parker, J. R. Colca, R. M. Fisher and R. F. Kletzein, Synthesis and Biological Activity of Metabolites of the Antidiabetic, Antihyperglycemic Agent Pioglitazone, J. Med. Chem., 1996, 39, 5053–5063; (k) S. A. Mosure, J. Shang, J. Eberhardt, R. Brust, J. Zheng, P. R. Griffin, S. Forli and D. J. Kojetin, Structural Basis of Altered Potency and Efficacy Displayed by a Major in Vivo Metabolite of the Antidiabetic PPARY Drug Pioglitazone, J. Med. Chem., 2019, 62, 2008–2023; (l) S. Dutta, H. Abe, S. Aoyagi, C. Kibayashi and K. S. Gates, DNA Damage by Fasicularin, J. Am. Chem. Soc., 2005, 127, 15004–15005; (m) I. C. Piña, J. T. Gautschi, G. Y. S. Wang, M. L. Sanders, F. J. Schmitz, D. France, S. Cornell-Kennon, L. C. Sambucetti, S. W. Remiszewski, L. B. Perez, K. W. Bair and P. Crews, Psammaplins from the Sponge Pseudoceratina purpurea: Inhibition of Both Histone Deacetylase and DNA Methyltransferase, J. Org. Chem., 2003, 68, 3866–3873.
2. For selected references, see: (a) G. Segalovich-Gerendash, I. Rozenberg, N. Alassad, N. B. Nechmad, I. Goldberg, S. Kozuch and N. G. Lemcoff, Imposing Latency in Ruthenium Sulfoxide-Chelated Benzylidenes: Expanding Opportunities for Thermal and Photoactivation in Olefin Metathesis, ACS Catal., 2020, 10, 4827–4834; (b) C. Maurya, A. Mazumder and P. K. Gupta, Phosphorus pentasulfide mediated conversion of organic thiocyanates to thiols, Beilstein J. Org. Chem., 2017, 13, 1184–1188; (c) J. V. N. V. Prasad, Synthesis of Heterocyclic Thiosulfonates, Org. Lett., 2000, 2, 1069–1072; (d) B. Robillard, L. Hughes, M. Slaby, D. A. Lindsay and K. U. Ingold, Synthesis of 2-substituted 5,7,8-trimethyl-6-hydroxythiochromans and purported syntheses of sulfur-containing analogs of vitamin E, J. Org. Chem., 1986, 51, 1700–1704.
3. For selected references, see: (a) A. R. Hajipour, R. Pourkaveha and H. Karimia, Synthesis of diaryl thioethers from aryl halides and potassium thiocyanate, Appl. Organomet. Chem., 2014, 28, 879–883; (b) F. Ke, Y. Qu, Z. Jiang, Z. Li, D. Wu and X. Zhou, An Efficient Copper-Catalyzed Carbon−Sulfur Bond Formation Protocol in Water, Org. Lett., 2011, 13, 454–457; (c) M. Gulea, F. Hammerschmidt, P. Marchand, S. Masson, V. Pisljagic and F. Wuggenig, Synthesis of chiral, nonracemic α-sulfanylphosphonates and derivatives, Tetrahedron: Asymmetry, 2003, 14, 1829–1836; (d) I. W. J. Still, Toste D, Reduction of Aryl Thiocyanates with SmI₂ and Pd-Catalyzed Coupling with Aryl Halides as a Route to Mixed Aryl Sulfides, J. Org. Chem., 1996, 61, 7677–7680.
4. For selected references, see: (a) Y. G. Kim, H. N. Lim and K. J. Lee, A new route to allyl thiols and allyl thiocarbamates from Baylis-Hillman adducts, J. Heterocycl. Chem., 2009, 46, 23–27; (b) J. R. Falck, S. Gao, R. N. Prasad and S. R. Koduru, Electrophilic α-thiocyanation of chiral and achiral N-acyl imides. A convenient route to 5-substituted and 5,5-disubstituted 2,4-thiazolidinediones, Bioorg. Med. Chem. Lett., 2008, 18, 1768–1771; (c) A. Klásek, V. Mrkvička, A. Pevec and J. Košmrlj, Novel Tandem Hydration/Cyclodehydration of α-Thiocyanatoketones to 2-Oxo-3-thiazolines. Application to Thiazolo[5,4-c]quinoline-2,4(3aH,5H)-dione Synthesis, J. Org. Chem., 2004, 69, 5646–5651; (d) A. K. Shiryaev and I. K. Moiseev, Adamantylation of Thiocyanatoacetamide and Thiocyanatoacetylurea, Russ. J. Org. Chem., 2001, 37, 746–747.
5. For selected references, see: (a) R. Chandran, A. Pise, S. K. Shah, D. Rahul, V. Suman and K. Tiwari, Copper-Catalyzed Thiolation of Terminal Alkynes Employing Thiocyanate as the Sulfur Source Leading to Enaminone-Based Alkynyl Sulfides under Ambient Conditions, Org. Lett., 2020, 22, 6557–6561; (b) L. Yang, Z. Y. Tian and C. P. Zhang, Transition-Metal-Free Selective Synthesis of (Z,)-1,2-Diarylthio-1-arylalkenes, (2-Arylethene-1,1,2-triyl)tris(arylsulfane)s and Alkynyl Sulfides from Thiocyanates and Terminal Arylalkynes, ChemistrySelect, 2019, 4, 311–315.
6. For selected references, see: (a) J. Yadav, B. S. Reddy, S. Shubashree and K. Sadashiv, Iodine/MeOH: a novel and efficient reagent system for thiocyanation of aromatics and heteroaromatics, Tetrahedron Lett., 2004, 45, 2951–2954; (b) X. Q. Pan, M. Y. Lei, J. P. Zou and W. Zhang, Mn(OAc) ₃-p romoted regioselective free radical thiocyanation of indoles and anilines, Tetrahedron Lett., 2009, 50, 347–349; (c) W. Fan, Q. Yang, F. Xu and P. Li, A Visible-Light-Promoted Aerobic Metal-Free C-3 Thiocyanation of Indoles, J. Org. Chem., 2014, 79, 10588–10592; (d) D. Yang, K. Yan, W. Wei, G. Li, S. Lu, C. Zhao, L. Tian and H. Wang, Catalyst-Free Regioselective C-3 Thiocyanation of Imidazopyridines, J. Org. Chem., 2015, 80, 11073–11079; (e) M. Barbero, I. Degani, N. Diulgheroff, S. Dughera and R. Fochi, Improved Procedure to Aryl Thiocyanates: A New Synthetic Application of Dry Arenediazonium o-Benzenedisulfonimides, Synthesis, 2001, 585–590; (f) Y. F. Wang, Y. Zhou, J. R. Wang, L. Liu and Q. X. Guo, CuI-catalyzed Synthesis of Aryl Thiocyanates from Aryl Iodides, Chin. Chem. Lett., 2006, 17, 1283–1386; (g) N. Sun, L. Che, W. Mo, B. Hu, Z. Shen and X. Hu, A mild copper-catalyzed aerobic oxidative thiocyanation of arylboronic acids with TMSNCS, Org. Biomol. Chem., 2015, 13, 691–696; (h) H. F. Jiang, W. Yu, X. Tang, J. Li and W. Q. Wu, Copper-Catalyzed Aerobic Oxidative Regioselective Thiocyanation of Aromatics and Heteroaromatics, J. Org. Chem., 2017, 82, 9312–9320.
7. For selected references, see: (a) Y. Ju, D. Kumar and R. S. Varma, Revisiting Nucleophilic Substitution Reactions: Microwave-Assisted Synthesis of Azides, Thiocyanates, and Sulfones in an Aqueous Medium, J. Org. Chem., 2006, 71, 6697–6700; (b) J. S. Qiu, D. Wu, P. G. Karmaker, H. Q. Yin and F. X. Chen, Enantioselective Organocatalyzed Direct α-Thiocyanation of Cyclic β-Ketoesters by N-Thiocyanatophthalimide, Org. Lett., 2018, 20, 1600–1603; (c) D. Wu, J. S. Qiu, P. G. Karmaker, H. Q. Yin and F. X. Chen, N-Thiocyanatosaccharin: A “Sweet” Electrophilic Thiocyanation Reagent and the Synthetic Applications, J. Org. Chem., 2018, 83, 1576–1583; (d) J. Jiao, L. X. Nguyen, D. R. Patterson and R. A. Flowers, An Efficient and General Approach to β-Functionalized Ketones, Org. Lett., 2007, 9, 1323–1326; (e) Y. T. Chen, S. F. Wang, Q. W. Jiang, C. G. Cheng, X. H. Xiao and G. G. Zhu, Palladium-Catalyzed Site-Selective sp³ C–H Bond Thiocyanation of 2-Aminofurans, J. Org. Chem., 2018, 83, 716–722; (f) C. Xu, Z. He, X. Kang and Q. L. Zeng, Highly selective radical isothiocyano-chalcogenization of alkenes with NH₄SCN in water, Green Chem., 2021, 23, 7544–7548; (g) P. Natarajan, Priya and D. Chuskit, Peroxodisulfate-assisted three-component benzylation of coumarins with styrenes and KSCN: a transition-metal-free approach for the synthesis of 3-(1-aryl-2-thiocyanatoethyl)-2H-chromen-2-one in ethyl lactate, Green Chem., 2021, 23, 4873–4881.
8. For selected references, see: (a) K. Tamao, T. Kakui and M. Kumada, (E)-alkenyl thiocyanates from (E)-alkenylpentafluorosilicates by the oxidative cleavage with copper(II) thiocyanate, Tetrahedron Lett., 1980, 21, 111–114; (b) T. Kitamura, S. Kobayashi and H. Taniguchi, Photolysis of vinyl halides. Reaction of photogenerated vinyl cations with cyanate and thiocyanate ions, J. Org. Chem., 1990, 55, 1801–1805; (c) J. Yan, H. W. Jin and Z. C. Chen, Study on the Stereoselective Reactions of Vinyl(phenyl)Iodonium Salts with Sodium Selenide, Sodium Sulfide, Sodium Azide and Potassium Thiocyanate, J. Chem. Res., 2007, 233–235; (d) Y. Tanabe, K. Mori and N. Kawabata, Phosphorus, Sulfur Silicon Relat. Elem., 1997, 120, 385; (e) S. Yang, T. He, D. Lin and J. M. Huang, Electrosynthesis of (E)-Vinyl Thiocyanates from Cinnamic Acids via Decarboxylative Coupling Reaction, Org. Lett., 2019, 21, 1958–1962.
9. For selected references, see: (a) O. Prakash, V. Sharma, H. Batra and R. M. Moriarty, (Dichloroiodo)benzene and lead(II) thiocyanate as an efficient reagent combination for stereoselective 1,2-dithiocyanation of alkynes, Tetrahedron Lett., 2001, 42, 553–555; (b) G. B. Jiang, C. L. Zhu, J. X. Li, W. Q. Wu and H. F. Jiang, Silver-Catalyzed Regio- and Stereoselective Thiocyanation of Haloalkynes: Access to (Z)-Vinyl Thiocyanates, Adv. Synth. Catal., 2017, 359, 1208–1212; (c) C. Wu, L. H. Lu, A. Z. Peng, G. K. Jia, C. Peng, Z. Cao, Z. L. Tang, W. M. He and X. H. Xu, Ultrasound-promoted Brønsted acid ionic liquid-catalyzed hydrothiocyanation of activated alkynes under minimal solvent conditions, Green Chem., 2018, 20, 3683–3688; (d) X. H. Zeng and L. Chen, Iodine-mediated regio- and stereoselective iodothiocyanation of alkynes in aqueous ethanol, Org. Biomol. Chem., 2018, 16, 7557–7560.
10. S. Chen, Q. Yan, J. Fan, Y. Gao, X. Yang, L. J. Li, Z. Q. Liu and Z. J. Li, Photoinduced cascade cyclization of alkynes with NH₄SCN: access to SCN-containing dibenzazepines or dioxodibenzothiazepines, Green Chem., 2022, 24, 4742–4747.
11. For representative references, see: (a) A. R. Díaz-Marrero, G. Porras, Z. Aragón and J. M. de la Rosa, Dorta E, Cueto M, D'Croz L, Maté J, Darias J. Carijodienone from the Octocoral Carijoa multiflora. A Spiropregnane-Based Steroid, J. Nat. Prod., 2011, 74, 292–295; (b) S. Kotha, A. C. Deb, K. Lahiri and E. Manivannan, Selected Synthetic Strategies to Spirocyclics, Synthesis, 2009, 165–193; (c) J. F. Hu, H. Fan, J. Xiong and S. B. Wu, Discorhabdins and Pyrroloiminoquinone-Related Alkaloids, Chem. Rev., 2011, 111, 5465–5491; (d) W. T. Wu, L. Zhang and S. L. You, Catalytic asymmetric dearomatization (CADA) reactions of phenol and aniline derivatives, Chem. Soc. Rev., 2016, 45, 1570–1580.
12. For representative references, see: (a) A. R. Pape, K. P. Kaliappan and E. P. Kündig, Transition-Metal-Mediated Dearomatization Reactions, Chem. Rev., 2000, 100, 2917–2940; (b) A. H. Bansode, S. R. Shaikh, R. G. Gonnade and N. T. Patil, Intramolecular ipso-arylative cyclization of aryl-alkynoates and N-arylpropiolamides with aryldiazonium salts through merged gold/visible light photoredox catalysis, Chem. Commun., 2017, 53, 9081–9084; (c) L. Yang, H. Zheng, L. Luo, J. Nan, J. Liu, Y. Wang and X. Luan, Palladium-Catalyzed Dynamic Kinetic Asymmetric Transformation of Racemic Biaryls: Axial-to-Central Chirality Transfer, J. Am. Chem. Soc., 2015, 137, 4876–4879; (d) J. Nan, Z. Zuo, L. Luo, L. Bai, H. Zheng, Y. Yuan, J. Liu, X. Luan and Y. Wang, Ru^II-Catalyzed Vinylative Dearomatization of Naphthols via a C(sp²)–H Bond Activation Approach, J. Am. Chem. Soc., 2013, 135, 17306–17309; (e) L. Ding, W. T. Wu, L. Zhang and S. L. You, Construction of Spironaphthalenones via Gold-Catalyzed Intramolecular Dearomatization Reaction of β-Naphthol Derivatives, Org. Lett., 2020, 22, 5861–5865.
13. For representative references, see: (a) J. J. Farndon, X. Ma and J. F. Bower, Transition Metal Free C–N Bond Forming Dearomatizations and Aryl C–H Aminations by in Situ Release of a Hydroxylamine-Based Aminating Agent, J. Am. Chem. Soc., 2017, 139, 14005–14008; (b) Y. Zhou, X. Zhang, Y. Zhang, L. Ruan, J. Zhang, D. Zhang-Negrerie and Y. Du, Iodocyclization of N-Arylpropynamides Mediated by Hypervalent Iodine Reagent: Divergent Synthesis of Iodinated Quinolin-2-ones and Spiro[4,5]trienones, Org. Lett., 2017, 19, 150–153; (c) R. P. Singh, J. Das, M. Yousufuddin, D. Gout and C. J. Lovely, Tandem Oxidative Dearomatizing Spirocyclizations of Propargyl Guanidines and Ureas, Org. Lett., 2017, 19, 4110–4113; (d) P. Fedoseev, G. Coppola, G. M. Ojeda and E. V. Van der Eycken, Synthesis of spiroindolenines by intramolecular ipso-iodocyclization of indol ynones, Chem. Commun., 2018, 54, 3625–3628; (e) P. Fedoseev and E. V. Van der Eycken, Temperature switchable Brønsted acid-promoted selective syntheses of spiro-indolenines and quinolines, Chem. Commun., 2017, 53, 7732–7735.
14. For representative references, see: (a) C. Y. Jin, J. Y. Du, C. Zeng, X. H. Zhao, Y. X. Cao, X. Z. Zhang, X. Y. Lu and C. A. Fan, Hypervalent Iodine(III)-Mediated Oxidative Dearomatizing Cyclization of Arylamines, Adv. Synth. Catal., 2014, 356, 2437–2444; (b) L. Pouységu, D. Deffieux and S. Quideau, Hypervalent iodine-mediated phenol dearomatization in natural product synthesis, Tetrahedron, 2010, 66, 2235–2261; (c) A. Rudolph, P. H. Bos, A. Meetsma, A. J. Minnaard and B. L. Feringa, Catalytic Asymmetric Conjugate Addition/Oxidative Dearomatization Towards Multifunctional Spirocyclic Compounds, Angew. Chem., Int. Ed., 2011, 50, 5834–5838.
15. For representative references, see: (a) D. Ryzhakov, M. Jarret, J. P. Baltaze, R. Guillot, C. Kouklovsky and G. Vincent, Synthesis of 3,3-Spirocyclic 2-Phosphonoindolines via a Dearomative Addition of Phosphonyl Radicals to Indoles, Org. Lett., 2019, 21, 4986–4990; (b) D. Ryzhakov, M. Jarret, R. Guillot, C. Kouklovsky and G. Vincent, Radical-Mediated Dearomatization of Indoles with Sulfinate Reagents for the Synthesis of Fluorinated Spirocyclic Indolines, Org. Lett., 2017, 19, 6336–6339; (c) W. C. Yang, M. M. Zhang and J. G. Feng, Recent Advances in the Construction of Spiro Compounds via Radical Dearomatization, Adv. Synth. Catal., 2020, 362, 4446–4461; (d) H. Zhang, Z. Gu, P. Xu, H. Hu, Y. Cheng and C. Zhu, Metal-free tandem oxidative C(sp³)–H bond functionalization of alkanes and dearomatization of N-phenyl-cinnamamides: access to alkylated 1-azaspiro[4.5]decanes, Chem. Commun., 2016, 52, 477–480; (e) X. H. Ouyang, R. J. Song, B. Liu and J. H. Li, Synthesis of 3-alkyl spiro[4,5]trienones by copper-catalyzed oxidative ipso-annulation of activated alkynes with unactivated alkanes, Chem. Commun., 2016, 52, 2573–2576.
16. For representative references, see: (a) Y. Zhang, J. Zhang, B. Hu, M. Ji, S. Ye and G. Zhu, Synthesis of Difluoromethylated and Phosphorated Spiro[5.5]trienones via Dearomative Spirocyclization of Biaryl Ynones, Org. Lett., 2018, 20, 2988–2992; (b) W. Dong, Y. Yuan, X. Xie and Z. Zhang, Visible-Light-Driven Dearomatization Reaction toward the Formation of Spiro[4.5]deca-1,6,9-trien-8-ones, Org. Lett., 2020, 22, 528–532; (c) D. Xia and X. F. Duan, Alkylative Dearomatization by Using an Unactivated Aryl Nitro Group as a Leaving Group: Access to Diversified Alkylated Spiro[5.5]trienones, Org. Lett., 2021, 23, 2548–2552; (d) H. E. Ho, A. Pagano, J. A. Rossi-Ashton, J. R. Donald, R. G. Epton, J. C. Churchill and M. J. James, O'Brien P, Taylor RJK, Unsworth WP. Visible-light-induced intramolecular charge transfer in the radical spirocyclisation of indole-tethered ynones, Chem. Sci., 2020, 11, 1353–1360; (e) C. Li, L. Xue, J. Zhou, Y. Zhao, G. Han, J. Hou, Y. Song and Y. Liu, Copper-Catalyzed Trifluoromethylation of Ynones Coupled with Dearomatizing Spirocyclization of Indoles: Access to CF₃-Containing Spiro[cyclopentane-1,3′-indole, Org. Lett., 2020, 22, 3291–3296; (f) D. P. Jin, P. Gao, D. Q. Chen, S. Chen, J. Wang, X. Y. Liu and Y. M. Liang, AgSCF₃-Mediated Oxidative Trifluoromethythiolation of Alkynes with Dearomatization to Synthesize SCF₃-Substituted Spiro[4,5]trienones, Org. Lett., 2016, 18, 3486–3489; (g) L. Zhou, Y. Xia, Y. Z. Wang, J. D. Fang and X. Y. Liu, Mn(III)-promoted synthesis of spiroannular tricyclic scaffolds via sulfonylation/dearomatization of biaryl ynones, Tetrahedron, 2019, 75, 1267–1274.
17. For representative references, see: (a) X. H. Yang, X. H. Ouyang, W. T. Wei, R. J. Song and J. H. Li, Nitrative Spirocyclization Mediated by TEMPO: Synthesis of Nitrated Spirocycles from N-Arylpropiolamides, tert-Butyl Nitrite and Water, Adv. Synth. Catal., 2015, 357, 1161–1166; (b) B. Tang, Q. Yin, R. Tang and J. H. Li, Electrophilic ipso-Cyclization of N-(p-Methoxyaryl)propiolamides Involving an Electrophile-Exchange Process, J. Org. Chem., 2008, 73, 9008–9011; (c) C. R. Reddy, U. Ajaykumar and D. H. Kolgave, Expeditious Access to Spiro-Fused 2,5-Cyclohexadienones via Thio(seleno)cyanative ipso-Cyclization, J. Org. Chem., 2020, 85, 15521–15531; (d) P. Chen, J. Fan, W. Yu, B. Xiong, Y. Liu, K. Tang and J. Xie, Alkylation/Ipso-cyclization of Active Alkynes Leading to 3-Alkylated Aza- and Oxa-spiro[4,5]-trienones, J. Org. Chem., 2022, 87, 5643–5659.
18. For representative references, see: (a) Y. Zhang, C. Ma, J. Struwe, J. Feng, G. G. Zhu and L. Ackermann, Electrooxidative dearomatization of biaryls: synthesis of tri- and difluoromethylated spiro[5.5]trienones, Chem. Sci., 2021, 12, 10092–10096; (b) W. C. Yang, M. Zhang, Y. Sun, C. Chen and L. Wang, Electrochemical Trifluoromethylthiolation and Spirocyclization of Alkynes with AgSCF₃: Access to SCF₃-Containing Spiro[5,5]trienones, Org. Lett., 2021, 23, 6691–6696; (c) F. Chen, Y. Zheng, H. Yang, Q. Yang, L. Wu and N. N. Zhou, Iron-Catalyzed Silylation and Spirocyclization of Biaryl-Ynones, A Radical Cascade Process toward Silylated Spiro[5.5]trienones, Adv. Synth. Catal., 2022, 364, 1537–1542; (d) D. Xia and X. F. Duan, Iron-Catalyzed Dearomatization of Biaryl Ynones with Aldehydes via Double C–H Functionalization in Eco-Benign Solvents: Highly Atom-Economical Synthesis of Acylated Spiro[5.5]trienones, J. Org. Chem., 2021, 86, 15263–15275; (e) C. R. Reddy and D. H. Kolgave, Electrochemical Selenylative Carbannulation of Biaryl Ynones to Seleno-Dibenzocycloheptenones/Spiro[5.5]Trienones, J Org. Chem., 2021, 86, 17071–17081; (f) H. Goulart, R. Bartz, T. Peglow, A. Barcellos, R. Cervo, R. Cargnelutti, R. Jacob, E. Lenardão and G. Perin, J. Org. Chem., 2022, 87, 4273–4283; (g) Z. Chen, X. Zheng, S. F. Zhou and X. L. Cui, Visible light-induced selenylative spirocyclization of biaryl ynones toward the formation of selenated spiro[5.5]trienones, Org. Biomol. Chem., 2022, 20, 5779–5783; (h) J. Li, Z. Li, L. Shen, P. Li, Y. Zhang and W. C. Yang, Synthesis of polychloromethylated and halogenated spiro[5,5]trienones via dearomative spirocyclization of biaryl ynones, Org. Biomol. Chem., 2022, 20, 6659–6666; (i) L. Shen, Y. Sun, Y. Wang, B. Li, W. C. Yang and P. Dai, K₂S₂O₈-promoted radical trifluoromethylthiolation/spirocyclization for the synthesis of SCF₃-featured spiro[5,5]trienones, Tetrahedron, 2022, 106, 132649–132652.
19. (a) Z. J. Li, X. Cui, L. Niu, Y. Ren, M. Bian, X. Yang, B. Yang, Q. Yan and J. Zhao, An Iron(II) Chloride-Promoted Radical Cascade Methylation or α-Chloro-β-methylation of N-Arylacrylamides with Dimethyl Sulfoxide, Adv. Synth. Catal., 2017, 359, 246–249; (b) R. Zhang, H. Yu, Z. J. Li, Q. Yan, P. Li, J. Wu, J. Qi, M. Jiang and L. Sun, Iron-Mediated Azidomethylation or Azidotrideuteromethylation of Active Alkenes with Azidotrimethylsilane and Dimethyl Sulfoxide, Adv. Synth. Catal., 2018, 360, 1384–1388; (c) Y. Ge, Y. Tian, J. Wu, Q. Yan, L. Zheng, Y. Ren, J. Zhao and Z. J. Li, Iron-promoted free radical cascade difunctionalization of unsaturated benzamides with silanes, Chem. Commun., 2020, 56, 12656–12659; (d) Y. Ren, Y. Ge, Q. Yan, S. Chen, Y. Li, L. Li, Z. Q. Liu and Z. J. Li, Free Radical-Promoted Monochloroalkylarylation of Alkenes with Chloralkanes, J. Org. Chem., 2021, 86, 12460–12466; (e) Y. Ren, Q. Yan, Y. Li, Y. Gao, J. Zhao, L. J. Li, Z. Q. Liu and Z. J. Li, Free Radical Promoted Trifluoromethylthiolation of Alkynes to Access SCF₃-Containing Dibenzazepines or Dioxodibenzothiazepines, J. Org. Chem., 2022, 87, 8773–8781.
20. For selected references, see: (a) Y. Ban, J. Dai, X. Jin, Q. Zhang and Q. Liu, Thiocyanate radical mediated dehydration of aldoximes with visible light and air, Chem. Commun., 2019, 55, 9701–9704; (b) P. Yuan, Q. Zhang, X. Jin, W. Lei, L. Z. Wu and Q. Liu, Visible-light-promoted aerobic metal-free aminothiocyanation of activated ketones, Green Chem., 2018, 20, 5464–5468; (c) J. Zhou, P. Zhou, T. Zhao, Q. Ren and J. Li, (Thio)etherification of Quinoxalinones under Visible-Light Photoredox Catalysis, Adv. Synth. Catal., 2019, 361, 5371–5382; (d) L. Li, J. Li, Y. Sun, C. Luo, H. Qiu, K. Q. Tang, H. X. Liu and W. T. Wei, Visible-Light-Catalyzed Tandem Radical Addition/1,5-Hydrogen Atom Transfer/Cyclization of 2-Alkynylarylethers with Sulfonyl Chlorides, Org. Lett., 2022, 24, 4704–4709; (e) X. Yu, C. Zhang, L. Wang, J. Li, T. Li and W. T. Wei, The synthesis of seven- and eight-membered rings by radical strategies, Org. Chem. Front., 2022, 9, 4757–4781; (f) D. Wang, L. Li, F. Liu, H. Qiu, J. Li, J. F. Zhang, C. Deng and W. T. Wei, Fe-Catalyzed Selective Formal Insertion of Diazo Compounds into C(sp)–C(sp³) Bonds of Propargyl Alcohols: Access to Alkyne-Substituted All-Carbon Quaternary Centers, ACS Cent. Sci., 2022, 8, 1028–1034.
21. For selected references, see: (a) B. M. Trost, The Atom Economy – A Search for Synthetic Efficiency, Science, 1991, 254, 1471–1477; (b) R. A. Sheldon, The E Factor: fifteen years on, Green Chem., 2007, 9, 1273–1283.

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Footnote

† Electronic supplementary information (ESI) available. CCDC 2210351. For ESI and crystallographic data in CIF or other electronic format see DOI: https://doi.org/10.1039/d2gc03710f

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