Yes it is very important to degass by bubbling with argon before the addition of Pd(PPh3)4 and also during reaction

What is the ratio of halide to boronic acid?

Also, you should try to isolate and characterize some byproducts if you are having so much "failure". If you can obtain some analytical standards this will help you to optimize the method. Even crude NMR might give you some ideas.

What is the difference between the stuctures that did work and the structures that did not work? This can give hint as to mechanism causing the undesired reactivity.

Good luck.

Thank you for your answers.

I did a TLC to check the progress of the reaction, and in the failed cases, only yellow, brown and unclear color spots remained, not the green spot (product or precursor) I expected. Also, I did degassing procedure of solvents in every coupling reaction using freeze-pump-thaw cycling.

The difference of the structure in succeeded and failed coupling reaction was substituents at the bay position of the perylene moiety. Perylene dimers with N-alkyl and 3,4,5-trimethoxy benzyl ether substituents were successfully synthesized.

The ratio of halide to boronic acid was 2:1

Hi,

well the most straightforward thing would be to protect the nitrogen with a suitable protecting group, its extra 2 steps of course but the purification of the coupled product will also be easier on silica for obvious reasons.

Secondly the Nitrogen here could act as a ligand inviting side reactions - such as C-H activation, the benzyllic elimination, catalyst degradation etc (which would not be the case for the corresponding ether).

Additionally different solvent systems may provide a successful route to the desired product, e.g. water/MeOH/Toluene, Water/MeCN, EtOH/MeCN, EtOH (with few drops of water). Similarly KF as a base could be used to avoid nucleophilic species.

In my experience small changes in kinetics (by changing solvent for example) can lead to drastic changes in the reaction itself.

Cheers and good luck,

Kaspars

you should definitely try using some of the Pd-NHC catalysts that are commercially available (CAS number 884879-23-6 or 905459-27-0) to perform the coupling in EtOH using a mild base such as potassium carbonate.. this works usually without any precautions (such as inert atmosphere or anhydrous conditions) ..

see Article Insights into the catalytic activity of [Pd(NHC)(cin)Cl] (NH...

Article A Simple Synthetic Entryway into Palladium Cross-Coupling Catalysis

it works with chloride and bromide substrates and mostly boronic acids .. your substrate is very specific and you may have to optimize time and temperature to get the optimal conversion .. i have already coupled something similar to your substrate with no problems.. hope it helps.

It could be because of sterics. you can do a test reaction with phenyl boronic acid to see if you could SM the bromide starting material. 0.05 mol% of Pd (pph3)2Cl2 in around 1.5 M potassium carbonate in water, (2 equiv) typically works.

Dear T. G. Hwang,

No doubt Pd(PPd3)4 in THF/Water is a good condition for SM reaction towards synthesis of several similar compounds. But at some cases that may not give fruitful results even on maintaining inert conditions due to several factors like solubility, molecular stability to temperature, column purification etc., So, I would like to suggest you to have a trial with Pd(PPh3)2Cl2 in Toluene:EtOH:Water which may give you better result. And also I would like to recommend F.Nahra where Pd-NHCs are now playing a crucial role in SM couplings.