Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions

Alkynyl selenides were synthesized by a straightforward one-pot and three-step methodology, without the need of diselenides as starting reagents, under an oxygen atmosphere and using PEG 200 as the solvent. This procedure involves the in situ generation of dialkyl diselenides through a K3PO4-assisted reaction of an alkyl selenocyanate obtained by a nucleophilic substitution reaction between KSeCN and alkyl halides. Successive reaction with terminal alkynes in the presence of t-BuOK affords the corresponding alkyl alkynyl selenide in moderate to good yields. Finally, this methodology allowed the synthesis of 2-alkylselanyl-substituted benzofuran and indole derivatives starting from convenient 2-substituted acetylenes.


Materials and methods
KSeCN, methyl(phenyl)selane, alkyl and benzyl halides were all high-purity commercial samples and used without further purification. Terminal aryl acetylenes were synthesized according to known procedures, 1 from the geminal dibromoalkenes previously obtained by a Wittig-type reaction from the corresponding aldehydes employing CBr 4 and PPh 3 . 2 DMF, acetonitrile and DMSO absolute grade were used without further purification and stored over molecular sieves (4 Å).
Toluene and dioxane were distilled following standard procedures and stored over molecular sieves (4 Å). PEG 200, PEG 300, isopropanol and ethanol were used without further purification. All reaction products were isolated by radial chromatography (silica gel, pentane) from the reaction mixtures and characterized by 1 H, 13 C and 77 Se NMR spectroscopy and mass spectrometry. 1 H, 13 C and 77 Se NMR spectra were recorded at 400.16, 100.62 and 76.28 MHz, respectively on a Bruker 400 spectrometer, and all spectra were reported in  (ppm) relative to Me 4 Si, with CDCl 3 as a solvent. The chemical shifts in 77 Se spectra are given in ppm using diphenyl diselenide (PhSeSePh) diluted in CDCl 3 as an external standard (δ 463 ppm at 25 °C). Gas chromatographic analyses were performed on an Agilent 5890 with a flame-ionization detector, on a 30 m capillary column of a 0.32 mm × 0.25 m film thickness, with a 5% phenylpolysiloxane phase. GC-MS analyses were conducted on an Agilent 7890 employing a 30 m × 0.25 mm × 0.25 m with a 5% phenylpolysiloxane phase column. HRMS spectra were recorded on a micrOTOF II LC mass spectrometer. Ionization was achieved by atmospheric pressure chemical ionization (APCI) and the detection setup in the positive ion mode.

Experimental procedures and characterization data
General experimental procedure for the study of the effect of t-BuOK on the formation of n-
Finally, 1.5, 2.0 or 3.0 equiv of t-BuOK were also added and the mixture was stirred for further 2 h.
Then the reaction mixture was cooled to room temperature. Diethyl ether (15 mL) and water S4 (15 mL) were added and the mixture was stirred. The organic layer was separated and the aqueous layer was extracted with diethyl ether (2 × 15 mL). The combined organic extract was dried over anhydrous Na 2 SO 4 and the product was isolated by radial chromatography from the crude reaction mixture.
General experimental procedures for one-pot synthesis of alkynyl selenides (5) (Scheme 1B) The reactions were carried out in a 10 mL three-necked Schlenk tube, equipped with a magnetic stirrer and a PTFE tube (ID: 1 mm, OD: 2 mm) connected externally to a balloon filled with oxygen.
The tube was charged with PEG 200 (3.0 mL), verifying the correct bubbling of oxygen into the solvent. KSeCN (2, 0.25 mmol) and alkyl halide (3, 1.0 equiv) were added and stirred for 10 min at 100 °C. K 3 PO 4 (1.0 equiv) was then added and the mixture was stirred for 1 h. Finally, aryl acetylene (6, 1.0 equiv) and t-BuOK (2.0 equiv) were also added and the mixture was stirred for further 2 h.