16 Jul 2012

Palladium-Catalyzed Biaryl Coupling Using PEPPSI Under Aqueous Microwave Conditions

Lab Experiment

Submitted by Gerard Rowe, University of South Carolina Aiken

This is a lab that gives students a chance to use a catalyst to perform "green" chemistry.  Specifically, they will make one of the new generation of palladium cross-coupling catalysts called PEPPSI, which is a highly active, water soluble catalyst and use it in a Suzuki coupling reaction.  Student groups of 2 or 3 will synthesize an NHC ligand, incorporate it into a metal compound, and then perform catalysis in an aqueous microwave reaction using a variety of different reaction conditions in order to determine the optimal catalytic system.

Learning Goals: 

A student should develop the skills to synthesize imidazolium salts for use in N-heterocyclic carbene ligands.

A student should learn some of the tenents of green chemistry, and be able to identify what qualifies a reaction as "green".

A student should be able to process a large set of catalytic reaction data in order to calculate turnover number, turnover frequency, and identify the optimum set of catalytic conditions.

Equipment needs: 


Rotary Evaporator

Vacuum line (optional, but very useful)

Microwave (a fancy microwave synthesis instrument is not necessary; we use an old acid digestion system, and it works just fine)

Microwave reaction vessels (Glass or Teflon works, but they need to be able to withstand ~150 PSI)





Ethyl acetate

Glyoxal (40 wt% in water)




Palladium(II) chloride

Phenylboronic acid





Hydrochloric acid (4.0 M in 1,4-dioxane)

Sodium bicarbonate

Diethyl ether




Tetraethylammonium chloride (or Tetrabutylammonium chloride)

Sodium dodecyl sulfate


Implementation Notes: 

Students tend to get poor yields on the synthesis of the imidazolium salt, and sometimes do not have enough to make the metal compound.  I keep a backup stash of IiPr*HCl that they can dip into if needed (usually with a penalty to their lab practical score).

The original prep for PEPPSI synthesis calls for vacuum distillation to recover the 3-chloropyridine.  I've found that we can get this done much more quickly and easily if we adjust the rotavap so that it is as close to horizontal as possible and use it as a sort of poor-man's Kugelrohr (Aldrich stopped selling their model, and the Buchi instrument is quite expensive).  For my class, the biggest bottleneck is waiting for the rotary evaporator, as our class meets at the same time as organic lab.  Also, since we are reclaiming the 3-chloropyridine solvent/reagent in Week 3, I really only trust them to use my personal rotavap, which is the only one in the department that isn't covered in stains.

It is usually a lot easier (and cheaper) to have the group that finishes their PEPPSI synthesis first take an NMR of the precatalyst and either print or email it to the entire class.

The catalysis itself works extremely well.  All students were able to get at least some product in one or both of their reactions, and some of the iterations gave quantitative yields.

Since a few of the reactions have a long stirring step that the class reaches at the same time, I use that opportunity to give a brief overview of what TON and TOF are, and how to calculate them.  By this point in the course, they should have seen at least one palladium catalyzed cross-coupling mechanism in lecture.  I leave it up to them to look up the difference between % conversion and % yield.

Time Required: 
3 3-4 hour lab periods + 15 minutes the week before lab starts
Evaluation Methods: 

This is a very synthesis-heavy lab, and I stress the need to get high yields in the ligand and metal compound syntheses, especially because we are using palladium in the final synthesis step.  Part of the students' scores is their lab practical grade that assesses yield, purity (by NMR), and whether or not they were successful in achieving catalysis (for those conditions that are known to work).

Students in my class also write a ~5 page ACS journal-style lab report.  In their introduction, they are free to focus on whatever aspect of the chemistry interests them, but they must have a comprehensive results and discussion section.  Students are given a page of questions (attached below) that they need to address in their text that help them to formulate their discussions.  

Evaluation Results: 

In my course, this is that last lab the class does as a group before they conduct their independently-chosen experiments.  Since they would have received about 4 graded lab reports back by this point, the writing style of the reports is generally acceptable.  I always require the class to write out a chemical reaction for any and all chemical reactions they carry out in lab.  

One other problem I notice when grading students' reports is that some tend to omit entire aspects of the experiment in their results and discussion sections (e.g., some will only talk about the ligand synthesis but leave out the metal complex synthesis).  Most of them remember to talk about the catalysis, since it was the last thing they did, but it seems like they could use a reminder to include all the sections of the lab in their report.  The attached report guidelines sheet was created to guide the students.

I was actually very surprised that so many members of my class had trouble designing a data table that effectively conveyed all the necessary information from the catalysis.  About a quarter of the class chose to give each iteration of the reaction its own column in the table, with the different conditions listed in the first column.  When I teach the lab again this year, I'll definitely take some time to show the class the best way to organize a large set of data in tabular form.


Creative Commons License: 
Creative Commons Licence

The VIPEr community supports respectful and voluntary sharing. Click here for a description of our default Creative Commons license.