Without copper it is a regular Huisgen-type 3+2 cycloaddition, a bit like Diels-Alder 4+2 cycloaddition.

In such a case rate, as Erkan Halay wrote - you get a mixture of regioisomers.

Rate of the reaction and composition of the mixture depend on the structure of the azide and alkyne. You get the best results without copper if you use an electron-poor alkyne like but-2-ynedioic acid ( HOOC-CC-COOH ).

You can also use fluorine-substituted cyclic alkynes like DIFO (1,1-difluoro-cyclooct-2-yne). They also readily react without copper (copper-free click chemistry).

It is an interesting observation you made for your compounds and certainly worth to note, however you need to take care about the regioselectivity of the reaction.

To get more information, maybe try searching for Huisgen cycloaddition regioselectivity in papers before 2001. Take care about the year - before 2001 only the "uncatalyzed" version was known.

Thank's for the very nice answers - i'll try too read up on it. But as I understand both of you, some reaction will occur without Cu+ but at a low rate. Erkan, I see much more product in the presence of Cu+, but I'm just curious how much product will be made without. Ideally I do not want any reaction to occur before I add Cu2+ & NaAsc.

Dear mikkel,

Your copper ligand increase the cinetic of the reaction, so if you do not want any reaction occur before the addition of Cu Asc, don't add the THPTA. 

If you want to control the beginning of your reaction, you should use the copper ligand instead of the copper.

Thank you Anthony, but in my control I'm not adding anything else than NaCl and incubating the same time as the reactions with Cu+2, NaAsc & ligand. Still some reaction seems to occur in the control....

Hi Mikkel,

Did you solve the problem, I met the same problem. Any suggestion?