Efficient Erbium-Catalyzed [ 3 + 2 ] Cycloaddition : 2 Regioselective Synthesis of 1 , 5-Disubstituted 1 , 2 , 3-3 Triazoles 4

A simple procedure to obtain 1,5-disubstituted 1,2,3-triazoles, using the catalytic system 13 erbium(III) trifluoromethanesulfonate, 1-methyl pyridinium trifluoromethanesulfonate and water 14 is described. The reaction proceeds through an eliminative azide–olefin cycloaddition (EAOC) 15 offering a highly regioselective approach and good yields (81–94%). The advantages of this method 16 include simple operations of work-up and the ability of the catalytic system to be re-used five times 17 without an evident loss in yield. 18

An alternative procedure to prepare 1,5-substituted triazoles is represented by eliminative azide-olefin cycloaddition (EAOC), in which azides are employed as dipole and electron deficient olefins are proposed to replace alkynes as dipolarophile.[29,30] The azide-olefin cycloaddition furnishes triazoline, an unstable compound that readily decompose but that may be transformed into the stable triazole by eliminative azide-olefin cycloaddition (EAOC).In particular, nitroolefins are revealed as excellent starting materials because of the presence of electron withdrawing nitro group both improves the 1,3-dipolar cycloaddition process, lowering the LUMO of the dipolarophile, and favors the formation of required 1,2,3-triazoles due to the fast nitrous acid loss through elimination step.[31]
We decided to explore prevalently 1-methyl pyridinium trifluoromethanesulfonate [mpy]OTf as ionic liquid for its easy one-step preparation through halide-free direct synthesis, by adding directly methyltrifluoromethanesulfonate to dry pyridine.[32] Moreover, triflate salts were only employed to avoid the simultaneous presence of different counteranions in the reaction system.
Without any catalyst, a mixture of 1,4-and 1,5-disubstituted triazoles were observed in very low yield after a long reaction time (entry 1, Table 1).Exploring between a number of triflate salts (entry 2-7,table 1) we found that the Er(OTf)3 was the most effective, carrying out the desired product in very high yield (entry 7, table 1).Halving the amount of reagent 2a only a 55% of 3a was obtained (entry 8, table 1), whereas, when the catalyst was decreased to 5 mol % (entry 9, table 1) the yield of final product was lower than that obtained using 10 mol% of catalyst.Additional experiments with different ionic liquids (entry 10-11, table 1), confirmed that the [mpy]OTf appeared to be the best choice.Probably, it may due to increased solvation of dipolarophile intermediate because of higher charge localization in piridynium cation than imidazolim cation.[33] Using our optimized experimental conditions, we investigated the reaction of various arylnitroolefins 1a-1n and phenylazide 2a or benzylazide 2b (Table 2).It is to note that nitroolefins bearing electron-withdrawing and electron-donors substituents were used as starting materials without observing considerable variations in the reaction path.
Furthermore, in all cases, it is good to highlight that the intermediate triazoline has never been isolated because it spontaneously evolves to the corresponding triazole by loss of HNO2.
At this point, we propose a possible reaction mechanism for the reaction of 1a with 2a as illustrated in Scheme 2. HNO2.The catalytic system [mpy]OTf/Er(TfO)3 has been analyzed with respect recovery and re-use in the reaction between ω-nitrostyrene 1a and benzylazide 2a and the results are shown in Table 3.The results of table 3 demonstrate that the [mpy]OTf/H2O/Er(OTf)3 system remains active until six cycles without loss of efficiency.

Materials and Methods
All chemicals purchased from common commercial sources were used as received without any further purification.Reactions were monitored by TLC using silica plates 60-F264, commercially available from Merck.

Synthesis of Ionic Liquids
1-Methyl pyridinium trifluoromethanesulfonate ([mpy]OTf) was prepared by halide-free direct synthesis in according to the procedure reported in the literature.[24,34] Recycling of the catalytic system IL/FeCl3 After the polar phase was extracted three times by dichloromethane, the ionic liquid/H2O/Er(OTf)3 system was washed with hexane and dried under vacuum condition.Successive runs were performed in the recycled catalytic system by reacting fresh reagents at the usual conditions.

Conclusions
In conclusion, we have realized an efficient route for the synthesis of 1,5-disubstitued-1,2,3triazoles using an eco-friendly catalytic system formed by erbium(III) trifluoromethanesulfonate, 1methyl pyridinium trifluoromethanesulfonate and water.The reactions proceed in a highly regioselective manner with the possibility to reuse of catalytic system until six cycles.This strategy has many advantages, for example high regioselectivity, good yields and experimentally convenient catalytic process, which could significantly direct further research of eco-friendly synthesis of 1,5disubstituted triazoles.

Supplementary Materials:
The following are available online at www.mdpi.com/xxx/s1.Funding: This research received no external funding.

Table 3 .
Recovery and re-use of catalytic [mpy]OTf/Er(OTf)3 system until six cycles 1H and13C NMR spectra were recorded at 300 MHz and 75 MHz, respectively, in CDCl3 using tetramethylsilane (TMS) as internal standard (Bruker ACP 300 MHz).Chemical shifts are given in parts per million and coupling constants in Hertz.LC-MS analysis were carried using an Agilent 6540 UHD Accurate -Mass Q-TOF LC-MS (Agilent, Santa Clara, CA) fitted with a electrospray ionization source (Dual AJS ESI) operating in positive ion mode.Chromatographic separation was achieved using a C18 RP analytical column (Poroshell 120, SB-C18, 50 x 2.1 mm, 2.7 mm) at 30 °C with a elution gradient from 5% to 95% of B over 13 min., a being H2O (0.1% FA) and B CH3CN (0.1% FA).Flow rate was 0.4 mL min -1 .