A Metal-Free, Aqueous and General Route to 1,5-Disubstituted-1,2,3-triazoles: ‘Reversed Regioisomeric’ 1,3-Dipolar Cycloaddition of Azides and Vinyl Sulfones

Abstract

A metal-free, vinyl sulfone-based synthesis of 1,5-disubstituted-1,2,3-triazoles is reported for the first time. These triazoles are easily formed in a regioselective fashion by heating under reflux a mixture of a substituted vinyl sulfone and an organic azide ‘on water’. This powerful and practical route has the potential to be exploited for the synthesis of complex 1,5-disubstituted-1,2,3-triazoles.

Key words

triazoles - on water - vinyl sulfone - organic azide - click chemistry

References and Notes

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15

For the synthesis of 11k from 5-azido-5-deoxy-2,3-O-isopropylidene-β-d-ribofuranoside, 2 equiv of NaHCO₃ was used in the reaction mixture to neutralize the acid generated after elimination. NaHCO₃ is not required for the synthesis of 2b-d, 11a-j or 11l-n.

20

General procedure for the synthesis of 1,5-disubstituted-1,2,3-triazoles (2b-d and 11a-n): A mixture of vinyl sulfone 6 or 10 (1 mmol), and azide (1.5 mmol for monoazide and 0.5 mmol for diazide) in water (10 mL/mmol of 6 or 10) was heated at reflux temperature for 3-19 h. After completion of the reaction (monitored by TLC) the reaction mixture was treated with sat. NaHCO₃ and the product was extracted with EtOAc (3 × 30 mL). The organic layer was dried over anhydrous Na₂SO₄, filtered, and the filtrate was evaporated to dryness under reduced pressure. The residue was purified by silica column chromatography to afford the corresponding 1,5-disubstituted-1,2,3-triazoles 2b-d and 11a-n.