Regarding Sonogashira: they always worked well for me. 3mol% Cu(I)-iodide, 5mol% Pd(PPh3)2Cl2 in DMF with 1.0equiv. of the aryl iodide. 1.2 equiv. of TEA added (everything at rt, the mixture was degassed thoroughly) and then 1.1equiv. acetylene was added. 2h at rt did the job in most cases. Prepared >20 examples with yields from 80 to 95%.
The Sonogashira coupling is what is giving me the problem, and I don't know why. Everyone else in my group is able to do it, and literature has a 99% yield for the substrate I'm trying to make but I get nothing! The literature I used the first time was JACS 2013 135 1264 from the supporting info. In the glove box I added my Pd(PPh3)2Cl2 (2 mol%) and my CuI (4 mol%), made sure no air got in and then added my iodobenzene derivative (1 eq) and in 2 ml of dried THF. Then I added my TEA (2 eq). I let that mix for a minute and then I add my TMS acetylene (1.5eq) dropwise over 3 minutes. Then added the rest of THF (0.4 ml) and let it stir under N2 over night. I use KMnO4 stain so when I saw something stain at a high Rf with hexane as my solvent front for TLC, I filtered the reaction over celite, and then removed the THF via rotavap. Then I extracted what was left with ethyl ether and water/brime 3x and dried with MgSO4. When I take and NMR of it looks like I have my amine and my TMS acetylene. No aromatic peaks revealing where my other starting material is.
I did the reaction again using a difference catalyst and a different procedure that showed the reaction yielding a 99% yield for my substrate. This is from Tetrahedron Letters 43 (2002) 7091. In my schlank tube I added Pd(PPh3)4(2 mol%), CuI (4 mol%) and TEA(1.5 eq) in THF (5ml) all under nitrogen. Then I let that stir for about a minute, added the iodobenzene derivative and then the reaction mitxure was cooled to 0 degrees. Let that stir for 10 minutes then added the TMS-acetylene (1.05 eq) dropwise over 30 minutes. The let it stir at room temp over night. Filtered with Celite and rotovapped the filtrate and just took an NMR of that because I thought my extraction methods were causing me to lose my stuff. However, I check the NMR and again I have the same result as yesterday - no aromatic peaks! I honestly want to pull my hair out, but I won't because I love my hair.
I talked to my labmates about it and they have no clue what is going on. So I decided to just do a test run with iodobenzene with Pd(PPh3)2Cl2 as my catalyst (since we are running out of the Pd(PPh3)4) and see how a test run goes. If it makes the alkyne then I have no idea what is going on with this substrate. If it doesn't than it is just me and I will have to just have my lab mates babysit me as I do this reaction because this is seriously ridiculous!
But whatever - chemistry, oh chemistry.