| 1 |
The straightforward introduction of the trifluoromethylseleno group into aromatic and heteroaromatic compounds is accomplished by the utilization of readily available aryldiazonium tetrafluoroborates, potassium selenocyanate, and Ruppert–Prakash reagent. The reaction tolerates a wide range of aromatic and heteroaromatic diazonium salts and is also amenable to the synthesis of pentafluoroethyl selenoethers. Furthermore, the methodology can be applied directly starting from anilines. |
| 2 |
Small perfluorinated groups can be found in numerous pharmaceuticals, agrochemicals, and materials. Compounds which possess fluorine-rich residues have usually different, improved biological and physical properties compared to their non-fluorinated analogs.1, 2, 3 Therefore, the introduction of such groups became an important topic in medicinal and pharmaceutical chemistry1 as well as agrochemistry. |
| 3 |
Recently, the SCF3 group turned out to be the subject of numerous investigations due to its unique properties, including high lipophilicity (Hansch constant pi=1.44), metabolic stability and electron withdrawing effect.4 To date, we have a general collection of basic procedures for the formation of C(sp, sp2, sp3)-SCF3 bonds that includes the straightforward introduction of a SCF3 group in a nucleophilic, electrophilic, or radical manner. |
| 4 |
In contrast to sulfur derivatives, selenium compounds are less applied6 although the SeCF3 group for instance provides a stable, more bulky, and more lipophilic functional group.4 Therefore, it is surprising that only few methods are known which allow the direct introduction of the SeCF3 group in a straightforward, convenient, and mild way, especially in aromatic and heteroaromatic substrates. |
| 5 |
Pioneering work from Yagupolskii and Haas, followed by Billiard, Langlois, and Dolbier7 disclosed the introduction of the SeCF3 group into molecules. Recently, Weng and co-workers reported elegant protocols for the synthesis of [{Cu(bpy)(SeCF3)}2] and [{Cu(phen)(SeCF3)}2] reagents, and showed their usefulness in reactions with aryl and heteroaryl halides.8 However, the above-mentioned methods still engage the usage of equimolar quantities of metals or pre-functionalized starting materials.9 Therefore, a simple one-pot procedure for the introduction of a SeCF3 group by employing a cheap and readily available metal salt as catalyst would be desirable. Hence, we decided to develop such a reaction starting from readily available diazonium salts. |
| 6 |
The Sandmeyer reaction is a powerful tool for the preparation of differently functionalized compounds starting from diazonium salts, which can be easily obtained from readily available anilines. The reactions are performed with or without catalytic amounts of Cu salts and typically do not show byproduct formations. Therefore, we wondered whether a copper-catalyzed Sandmeyer reaction for the introduction of selenium10 followed by a reaction with the Ruppert–Prakash reagent would give the trifluoromethylseleno-functionalized compounds.11, 12 This would in principle allow the preparation of different trifluoromethyl aryl selenides from anilines. |
| 7 |
Various reactions for the introduction of selenium atoms are highly dependent on the selenium source. Polymeric "grey" selenium shows very poor reactivity and often side products are formed. In contrast, amorphous "red" selenium is more reactive. However, it is less stable with regard to storage and thus needs to be prepared freshly prior to use. To overcome such obstacles we decided to use potassium selenocyanate, considering its availability, low price, and long-term shelf stability. |
| 8 |
Initially, p-methoxyphenyl diazonium tetrafluoroborate (1) was chosen as model substrate to react with potassium selenocyanate. Considering that the oxidation potential of NCSe- (Eo=-0.59 V)13b is similar to that of I- (Eo=-0.54 V),13c it is reasonable to assume that the reaction might occur without any catalyst. Indeed, upon treatment of 1 with KSeCN in dry CH3CN at r.t. for 15 min, evolution of nitrogen occurred and two products were isolated in 55 % total yield (Table 1, entry 1). The main product was obtained in 35 % yield after column chromatography and it was identified by 1H and 13C NMR spectroscopy and MS measurement to be p-methoxyphenyl selenocyanate 1 a′. As a second product we isolated bis(p-methoxyphenyl)selenide in 20 % yield. These results most probably relate to the ambident nucleophilicity of the selenocyanate anion and the different stability of the corresponding arylseleno- and arylisoselenocyanates. |
| 9 |
Hence, further investigations were targeted to suppress the side product formation by catalyst involvement. Cu salts are typical catalysts for the Sandmeyer reaction; hence, different Cu sources were tested. Interestingly, the desired p-methoxyphenylselenocyanate 1 a’ was almost exclusively formed (Table 1). CuI and CuII salts reacted equally well (Entries 2–8) and comparable results were obtained with catalytic as well as stoichiometric amounts of CuCl (Entries 4–6). We also tested heterovalent CuI/CuII systems14 (Entries 9–12). Pleasingly, with 10 mol % of a CuCl/CuCl2 system the desired product 1 a’ was obtained in 78 % yield. Further optimization disclosed 1,10-phenanthroline as appropriate ligand and the product was obtained in 82 % yield with little side product formation. |
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