Dear Aya Moneer,

There are at least several alternatives to THPTA and TBTA.

We have developed an efficient ligand for cycloaddition of aliphatic substrates in aqueous solvents in our research, but our paper is still under review. I will get back to you as soon as I am able to give some information.

In the meantime, you could have a look at these two publications, they describe ligands that may be efficient for aromatic substrates:

S. Ozçubukçu; E. Ozkal; C. Jimeno; M.A. Pericàs, Organic Letters 2009, 11, 4680–3

H. Hiroki; K. Ogata; S. Fukuzawa, Synlett 2013, 24, 843–846.

You could also have look at other papers:

R.J. Detz, S.A. Heras, R. De Gelder, P.W.N.M. Van Leeuwen, H. Hiemstra, J.N.H. Reek, J.H. Van Maarseveen, Organic Letters 8 (2006) 3227

S. Díez-Gonzlez, S.P. Nolan, Angew. Chemie - International Edition 47 (2008) 8881.

As I wrote in the previous answer, we have developed a water-soluble catalytic ligand for CuAAC. Our article has been accepted in Tetrahedron Letters and it is available online here:

http://www.sciencedirect.com/science/article/pii/S0040403915301520

In the article we present several efficient procedures using our ligand, AMTC, which improves the efficiency of copper-catalyzed azide-alkyne cycloaddition ,and a comparison with other known ligands - TBTA and THPTA

Thank You very much 

well , can the reaction proceed without addition of any ligand at all ? 

Yes, the reaction can proceed without a ligand, that is its "standard" version. You could simply use copper sulfate and sodium ascorbate in a water-alcohol mixture (water-ethanol or water-tert-butanol).

You could start with 10mol% of both Cu and ascorbate and then see if the reaction works. If it does not work too well, you can think about using ligand, if it works very good, you can try to reduce the amount of copper.

i find your experience very helpful , thanks 

one last thing .... is there a specific order of addition of the reagents ? and can it work on very small conc. in micro-gram scale of alkyne ?

As for the microgram scale, there should be no problem.

With the order of reagent addition, I usually add the solution of sodium ascorbate last to initiate the reaction. It is better to add it as solution because this way it is easier to avoid any uncontrolled processes.

If you have some difficulties with the reaction, e.g. some insoluble species may form, you may modify the addition order according to your system.