The NHK reaction is nicely described in this Wiki article. Catalytic amounts of nickel were found to be beneficial in this system and Kishi used the reaction extensively during his synthesis of Halichondrin B, to great effect.
During a rather long synthesis we were trying to convert an aldehyde to a cis-diene using the NHK reaction as one of the steps. For various reasons we were locked into using the chromous chloride from one particular supplier and they kept us a larger quantity of that batch for our future use. As far as I remember the Ni content was not specified but here the quality of chromous chloride is obviously critical for the success of this reaction and it had not been adequately defined. Indeed this may be a reason for the extreme variability we observed during a scale-up campaign that was in direct contrast to the previous campaign, where all the batches went to completion, without problems, in 2 hours at room temperature.
Now each of the three batch reactions behaved differently, the first was not complete after 2 hours and required more (20%) CrCl2 to be added with stirring for 18 hours at RT before it was complete.
Because of this hiccup, prior to the second batch we made sure that the reaction started by taking a small sample and running it in the lab. It behaved as we expected it worked. However, the second batch reaction did not budge one inch. Having a keen eye for detail I observed that the samples taken from the reactor for reaction monitoring had all proceeded rapidly to completion by the time it took to get them to the analytical lab, about ten to fifteen minutes. It was rationalised by others and myself that this may have been an effect due to the contact of the sample with air (oxygen). So here was the answer, take 150,000 mL samples and let them react. However, the others did not like this idea and suggested that we could/should introduce air into the reaction vessel! Two things to note here; 1) air (oxygen) is normally deadly for this type of reaction and 2) the introduction of air into a reactor full of 150 L of THF is a procedure that is fraught with hazard and should not be attempted at home, never mind the pilot plant. But the batteries were obviously in the correct way and lo and behold the reaction went to completion after a further 18-hour period.
The third batch, however, when run under the conditions used for the second batch (extra chromous chloride and a catalytic amount of air) did not move at all. As a last resort it was warmed to 40°C and obliged us by going to completion within 2 hours! I might add at this point that all the reagents and starting materials were use-tested before starting the larger scale batches, no problems were observed, all reactions going to completion within the allotted 2-hour period. I should also point out that the aldehyde was not that stable, as these things tend to be, we did see decomposition and racemisation after stability experiments, and we were running out of chromous chloride so we could not afford to fool around indefinitely.
The reason for this extreme variability and discrepancy from the lab results remains a total mystery and will need to be examined before any further scale-up is planned. However, it is known that catalytic quantities of nickel (II) or palladium (II) may be required for an efficient coupling process. We did not examine the nickel (II) content of our chromous chloride but this is a point we filed for future reference.
Furthermore the chromium residues cannot be present in the wastewater from the process therefore they must be re-cycled for an ecologically sound process although at this stage of development we did not investigate this. Truthfully I would not have known how to start doing this re-cycling and the above sentence is there for effect only. I would guess that somewhere in the literature I would find a paper referencing the preparation of an insoluble chromium(III) salt. I did not look, because the project died and I moved on to better things.
So in the words of the Bard, it is “just like cooking”.