Ultrasound-promoted synthesis of 2-organoselanyl-naphthalenes using Oxone® in aqueous medium as an oxidizing agent

A green methodology to synthesize 2-organoselanyl-naphthalenes based on the reaction of alkynols with diaryl diselenides is described. The electrophilic species of selenium were generated in situ, by the oxidative cleavage of the Se–Se bond of diaryl diselenides by Oxone® using water as the solvent. The reactions proceeded efficiently under ultrasonic irradiation as an alternative energy source, using a range of alkynols and diorganyl diselenides as starting materials. Through this methodology, the corresponding 2-organoselanyl-naphthalenes were obtained in moderate to good yields (56–94%) and in short reaction times (0.25–2.3 h).

In the last years, the use of ultrasonic waves as an alternative energy source in organic synthesis has exponentially increased. The so-called sonochemistry has the ability to accelerate, or even totally modify the reaction course, through the formation of new reactive intermediates that normally are not involved when conventional heating is used (Nowak, 2010;Mojtahedi & Abaee, 2012;Schiel et al., 2015). Recently, we have described new ultrasonic-promoted reactions, including the synthesis of 1,2,3-triazoyl carboxamides (Xavier et al., 2017), 3-selanylindoles (Vieira et al., 2015) and chrysin derivatives (Fonseca et al., 2017). Considering the importance of organoselenium compounds and naphthalene derivatives, and due our interest in green synthetic protocols associated to organochalcogen chemistry, we report herein a new ultrasound-promoted method to prepare 2-organoselanyl-naphthalenes 3a-i. Our strategy involves the carbocyclization of alkynols 2a-d using electrophilic selenium species, which were generated in situ by the reaction of diorganyl diselenides 1a-f with Oxone Ò (Fig. 1).

RESULTS AND DISCUSSION
The selenocyclization of alkynols with electrophilic selenium species is an efficient strategy to prepare organoselanyl-naphthalenes (Recchi, Back & Zeni, 2017). In our preliminary studies on the use of Oxone Ò as an oxidant to cleavage of Se-Se bond, we have observed that its reaction with diselenides generates highly reactive species in situ (Perin et al., 2018). Thus, by combining the selenocyclization strategy with the environmental and economic advantages of using Oxone Ò as an oxidizing agent, a study was carried out to evaluate the possibility of using it in selenocyclization reactions to prepare organoselanyl-naphthalenes. In our preliminary experiments, we choose diphenyl diselenide 1a and 1,4-diphenylbut-3-in-2-ol 2a as model substrates to establish the best conditions for the cyclization reaction promoted by Oxone Ò to synthesize the respective 2-organoselanyl-naphthalene 3a.
Initially, the reaction was performed using 0.25 mmol of alkynol 2a, 0.125 mmol of diphenyl diselenide 1a and 0.25 mmol of Oxone Ò , using ethanol (2.0 mL) as the solvent at 60 C under magnetic stirring. The desired product 3a was obtained in 78% yield after 72 h (Fig. 2, entry 1). To improve this result, some experiments were performed with the purpose of increasing the isolated yield and reducing the reaction time. The same reaction was then performed under ultrasonic irradiation (amplitude of 60%) and after 50 min, product 3a was obtained in 84% yield (Fig. 2, entry 2). Aiming to improve the yield of 3a, parameters as the nature of the solvent, quantities of the starting material 2a, amounts of Oxone Ò , and amplitude of the US were evaluated (Fig. 2, entries 3-12).
Regarding the influence of the solvent in the reaction, a range of solvents were tested and in reactions using polyethylene glycol-400 (PEG-400, Labsynth, Diadema, Brazil), glycerol, and DMF, product 3a was obtained in good yields (Fig. 2, entries 3, 4, and 8). To our satisfaction, a very good yield of 86% was obtained after sonication of the reaction mixture for 30 min in water (Fig. 2, entry 5). However, using dimethyl sulfoxide (DMSO) or acetonitrile as the solvent, only trace amounts of 3a were observed (Fig. 2, entries 6 and 7).
After water was defined as the best solvent for the reaction, the amplitude used in the ultrasound apparatus was evaluated. When the reaction was performed at 40% of amplitude, the desired product 3a was obtained in only 63% yield (Fig. 2, entry 9). It was observed that at this lower amplitude, the homogenization of the mixture was incomplete, what could negatively affect the reaction yield.
When an excess of alkynol 2a was used, total consumption of diphenyl diselenide 1a occurred after 30 min of reaction (monitored by TLC), however the yield of 3a was maintained (Fig. 2, entry 10). By using a lower amount of Oxone Ò (0.125 mmol), there was no total consumption of the starting materials after 2 h of reaction, and the desired product 3a was obtained in only 42% yield (Fig. 2, entry 11). Finally, the reaction was carried out in the absence of Oxone Ò and after 2 h none of product was formed (Fig. 2, entry 12). In order to verify the influence of the KHSO 4 species present in the reaction medium, a test was performed using 0.25 mmol of Oxone Ò together with 0.25 mmol of KHSO 4 and, after only 10 min of reaction, the starting materials were totally consumed, and the desired product 3a was obtained in 92% isolated yield, showing the need of generation of this species in the reaction medium (Fig. 2, entry 13). Thus, the best condition was defined as the sonication of a mixture of 0.125 mmol of diphenyl diselenide 1a and 0.25 mmol of alkynol 2a in the presence of 0.25 mmol of Oxone Ò in water (2.0 mL) for 30 min (Fig. 2, entry 5).
Once the best reaction conditions were determined, the methodology was extended to different substrates, in order to evaluate its generality and robustness in the synthesis of different 2-organoselanyl-naphthalenes 3a-i (Fig. 3). Firstly, the effect of electrondonor (EDG) and electron-withdrawing groups (EWG) attached to the aromatic ring of diselenide 1a-d was evaluated (Fig. 3, entries 1-4). It was observed that both EDG and EWG negatively affect the reaction, affording lower yields of the respective products. When diselenide 1b, containing a chlorine atom at the para position was used, there was a significant decrease in yield when compared to diphenyl diselenide 1a, and the respective naphthalene 3b was obtained in 63% yield (Fig. 3,  entry 2). Similarly, the electron-poor diselenide 1c, with a fluorine atom at the para position, afforded the respective naphthalene 3c in a moderate yield of 71% after 1.4 h (Fig. 3, entry 3).
The possibility of performing these reactions with other alkynols 2b-d was also investigated. Alkynols derived from phenylacetylene 2b and 2c, containing EDG and EWG at the aromatic ring, efficiently reacted with diphenyl diselenide 1a/Oxone Ò , affording the respective products 3g and 3h in 63 and 72% yields after 1.7 and 2.3 h, respectively (Fig. 3, entries 7 and 8). This result shows that the reaction is not sensitive the electronic effects of the substituents on the aromatic ring of the alkynols 2b and 2c. A remarkable positive effect was observed when an alkyl group was connected to the C sp of the alkynol, as in 2d and an excellent 94% yield of the expected naphthalene 3i was obtained after 1.0 h (Fig. 3, entry 9).
Based on our results and those from the literature (Zhang, Sarkar & Larock, 2006;Recchi, Back & Zeni, 2017;Perin et al., 2018), a plausible mechanism for the carbocyclization of alkynol 1a with (C 6 H 5 Se) 2 2a/Oxone Ò in aqueous medium is depicted in Fig. 4. The first step in the reaction is the oxidative cleavage of the Se-Se bond in diphenyl diselenide 2a by Oxone Ò , forming intermediates A and B (Perin et al., 2018). Once the electrophilic selenium species A is formed, it reacts with the carbon-carbon triple bond of the alkynol 1a to produce the seleniranium intermediate C. Following, an intramolecular 6-endo-dig cyclization occurs, giving intermediate D, which undergoes deprotonation to restoring the aromaticity of the system, forming the dihydronaphthalene E. Ultimately, water is eliminated to give the desired product 3a (Fig. 4).

CONCLUSION
A convenient, selective and eco-friendly methodology was developed for the synthesis of 2-organoselanyl-naphthalenes 3, using water as the solvent. The use of ultrasound as alternative energy source drastically reduces the reaction time, while increasing the reaction yield. This method involves the cyclization of properly substituted alkynols in the presence of electrophilic selenium species. Oxone Ò was shown to be an efficient and mild oxidizing agent for the oxidative cleavage of the Se-Se bond of diselenides in situ.

ADDITIONAL INFORMATION AND DECLARATIONS Funding
This work was supported by The Brazilian Council for Research and Technology (CNPq), CAPES and FAPERGS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.