Cu-Catalyzed solvent-free, pot-economic synthesis of 1,3-dynes from 1,1-dibromoalkenes in the presence of DBU • H 2 O

An efficient synthesis of 1,3-diynes directly from 1,1-dibromoalkenes has been achieved by utilizing hydrated 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU.H 2 O) as a sole reagent and a catalyst CuI. In general, 1,3-diynes were synthesized from corresponding terminal alkynes, which in turn were obtained from 1,1-dibromoalkenes. The DBU.H 2 O allowed the synthesis of 1,3-diynes not only in a pot-efficient manner but also under solvent-free conditions at ambient temperature. A plausible mechanism is proposed via 1-bromoalkynes intermediate instead of terminal alkynes.


Results and Discussion
We commenced our investigation by examining the reaction of 5-(2,2-dibromovinyl)-1,2,3-trimethoxybenzene 1a employing DBU as base and CuI as catalyst under solvent-free conditions.We have observed very low yields of product 2a (Entry 1, Table 1); this result is attributed to the observed exothermic reaction in the absence of solvent.Our attention then turned to milder base hydrated DBU (DBU.H2O) as a base instead of a strong base dry DBU, which was previously employed for the controlled solvent-free synthesis of 1-bromoalkynes from 1,1-dibromoalkenes.Subsequently, 1,1-dibromolakene 1a was subjected to reaction with DBU.H2O (2 mmol) and a catalytic amount of CuI (0.1 mmol) under solvent-free conditions at room temperature.To our delight, the reaction proceeded smoothly within 2 hours without forming any by-products and produced the only product 2a with a 96 % yield (Entry 2, Table 1).Inspired by this result, we screened this organic transformation to test the efficiency of mild base DBU.H2O and catalyst CuI with respect to time.When the reaction time was decreased to 1 hour and conducted the reaction by utilizing DBU.H2O (2 mmol) and a catalytic amount of CuI (0.1 mmol), we observed a reduced yield of product 2a (Entry 3, Table 1).Next, it was proved when this reaction was tested by reducing the Cu catalyst loading to 0.05 mmol gave further diminishing the yield of product 2a (Entry 4, Table 1).Additionally, we also conducted the reaction by reducing the loading of DBU.H2O to 1 mmol, gave the low yield of product 2a (Entry 5, Table 1).Finally, the optimization reaction conditions revealed that using 2 mmol of DBU.H2O and a catalytic amount of CuI (0.1 mmol) under the solvent-free condition at room temperature is a suitable condition to afford the desired product 2a in excellent yields (Entry 2, Table 1).In order to evaluate the substrate scope, various 1,1-dibromoalkenes 1a-q were treated with DBU.H2O and a catalytic amount of CuI using developed solvent-free conditions.All the reactions proceeded smoothly afforded the desired products 2a-q in good to excellent yields (Table 2).The reactions with substituted 1,1dibromoalkenes 1a-f having electron-donating group gave the desired products 2a-f in very good yields.Importantly, substrates bearing polyaromatic groups like naphthalene 1g and anthracene 1h also compatible with the conditions and gave the products 2g and 2h in 89% and 91% yields.The substrates containing electron-withdrawing groups substitution 1i-n were also well-tolerated and provided the corresponding products 2i-n in good yields.Heteroaromatic substituted substrates 1o, and 1p underwent this reaction smoothly and gave the desired products 2o and 2p in 91% and 96% yields, respectively.Significantly, the substrate, which has aryl-vinyl substitution 1q, afforded the desired product 2q in 84% yield without affecting the reaction rate.Further, we examined this organic transformation's scope to synthesize unsymmetrical diynes 2r and 2s (Scheme 2).Experiments were conducted by utilizing substrates containing two different substituted dibromides like 1m (1 mmol) and 1a (1 mmol) reacted to give the corresponding unsymmetrical diyne 2r in 54% yield.Due to the formation of some amounts of the corresponding homo coupled by-products 21% of 2m & 13% of 2a along with unsymmetrical diyne 54 % of 2r, chromatography was necessitated to separate the products.A similar reaction was carried out with substrates like enyne 1f with 1a, giving unsymmetrical enediyne product 2s in 42% and homocoupled products 2f and 2a in 25% and 11%, respectively.

Scheme 2. Synthesis of unsymmetrical diynes 2r & 2s.
On the other hand, we also conducted experiments on a gram scale to confirm the present protocol's efficiency and robustness.Treatment of 1a and 1f under the optimized conditions gave the desired products 2a and 2f in excellent yields (Scheme 3).
It is well known from literature 37 that 1,3-diynes can be straightforwardly obtained by treating terminal alkynes 3 using the Glaser-Hay coupling reaction.Further, based on the above results, our interest turned on to confirm the possible intermediate terminal alkyne or 1-bromoakyne involved in the reaction (Scheme 4).The developed solvent-free and pot-economic reaction was performed with 1,1-bromoalkyne 1a and base DBU.H 2 O alone without using copper catalyst at ambient temperature.Interestingly, only corresponding 1bromoalkyne 4a formed in good yield and there was neither 1,3-diyne 2a not expected terminal alkyne 3a formed.These results indicated that the reaction proceeds via alkynyl bromide 2a intermediate and not through terminal alkyne intermediate 3a.

Scheme 4. Mechanistic
Based on the above experimental results and previous reports, a plausible catalytic mechanism can be proposed for this organic transformation (Scheme 5).We assume this reaction proceeds through the formation 1-bromoalkyne 4 instead of terminal acetylene 3. Initially, the DBU.H2O acts as a base and eliminates HBr from dibromoalkene 1 would form bromoalkyne 4, which would further convert to complex A with Cu(I).Then, complex A added by another molecule of bromoalkyne 4 to generate dialkyne iodo complex B with Cu(III) and subsequently undergo reductive elimination to produce 1,3-diyne 2 and release the copper catalyst Cu(I).Scheme 5. A plausible reaction mechanism through 1-bromoalkyne intermediate.

Conclusions
In conclusion, we have developed a green and straightforward synthetic method to access 1,3-diynes at ambient temperature.The products can be obtained in pure form without chromatography purification technique leads to save time and solvents.The usage of hydrated DBU as the sole reagent can be evidenced as a better reagent than dry DBU. 56This method avoids the costly palladium catalysts, harsh reaction conditions, and usage of phosphine reagents/ligands.This method proves to be an efficient synthetic approach than the existing methods in the literature.

Experimental Section
General.All reactions were carried out in oven-dried reaction flasks under nitrogen atmosphere, and dry solvents and reagents were transferred by oven-dried syringes to ambient temperature.TLC was performed on Merck silica gel aluminium sheets, and solvents were removed under reduced pressure.Columns were packed as slurry of silica gel in hexane and ethyl acetate solvent mixture.The was assisted by applying pressure with an air pump. 13C NMR spectra were recorded on 101 MHz spectrometers. 1 H NMR spectra were recorded on 400 and 500 MHz spectrometers in appropriate solvents using TMS as an internal standard.The following abbreviations were used to explain multiplicities: s = singlet, d = doublet, dd = double doublet, t = triplet, m = multiplet.All reactions were performed at room temperature.Reagents were obtained from Aldrich, Alfa Aesar, and TCI used without further purification.All compounds are characterized by 1 H and 13 C NMR. Additionally, unknown compounds are characterized by HRMS analysis.All known compounds data are in consistent with the given literature report.

Table 1 .
Optimization of the reaction conditions a a Reaction conditions: all reactions were carried out with 1a and CuI in the presence of DBU.H 2 O at RT; b Yields of the isolated product.

Table 2 .
Substrate Scope 2 a a Reaction conditions: all reactions were carried out at room temperature, 1a (2 mmol) and CuI (0.1 mmol) in the presence of DBU.H2O; Yields are for isolated products.