Romero reports (relatively) brisk breakdown of B2Pin2

Citation:

 Hatcher, W.; Vanaparthi, S.; Young, M.; Romero, E. Contrary to Popular Belief, B2pin2 is Not Air Stable. Chemrxiv. 

Link to paper:

https://chemrxiv.org/doi/full/10.26434/chemrxiv-2025-rxj84

Summary Figure:

 

Background:

Thanks to the massive synthetic utility of the Suzuki-Miyaura coupling for making C-C bonds, borylated arenes are some of the most useful synthetic building blocks you can find. Personally, every lab I have been in has had some library of aryl boronic acids available. Arylboronic acids are a great way to quickly bang out a substrate scope, by attaching different heterocycles or functionalized arenes to a general substrate to evaluate functional group compatibility. 

 

Meanwhile, if you would like to make your own borylated arenes, there are two main established methods- Miyaura borylation and Hartwig-Smith borylation. 

Miyaura borylation is a Pd-catalyzed cross-coupling between a sp2-halide and B2pin2 (or related bis-boron compound). 

  

Hartwig-Smith borylation is an Ir-catalyzed C-H activation between an arene and B2pin2 (or related bis-boron comound). The method has been expanded over time to target a number of different possible C-H bonds, so it isn't limited to just arenes, and different catalysts and conditions can be used to selectively functionalize the desired position. 

Together with good old-fashioned lithiation-transmetalation with B2pin2 offers a number of ways to make boronic esters, which can then be hydrolyzed to make boronic acids if needed or desired. The key similarity between all three methods is that they rely on B2pin2 or another boronic ester dimer (B2nep2, etc.). It is much easier to make the boronic ester than to directly make the boronic acid. Additionally, all of these methods go through the dimer, which has a boron-boron bond. Activation of this bond, via either transmetalation or oxidative addition, is a key step in all 3 of the above strategies. 

For most of these examples, I've used B2pin2 as the borylation reagent of choice. B2pin2 is popular in the literature because (a) it works in most cases and (b) it's commercially available and allegedly very stable:

 

(From wikipedia)

The source from this originates from an Org Syntheses prep to synthesize B2pin2. 

Ishiyama, T.; Murata, M.; Ahiko, T.-a.; Miyaura, N., Bis(pinacolato)diboron. Org Synth 2000, 77, 176-180. https://www.orgsyn.org/demo.aspx?prep=v77p0176 

I'll note that the original text states: "Crystalline bis(pinacolato)diboron can be handled in air and stored in a capped bottle"

This does not state that the B2pin2 is infinitely stable, only that it does not react immediately with air or quickly degrade. 

The Young and Romero labs had some amount of personal experience (Erik Romero worked on borylation reactions with John Hartwig, so he definitely spent quality time with B2pin2) that suggested B2pin2 might not be shelf stable, or at least that the bottle could go bad at some point. While it's not uncommon for a bottle to no longer perform as well, usually this happens with sensitive reagents with an obvious decomposition pathway. For example, if a reagent with an indole stops performing well in reactions, oxidation of the heterocycle is a likely culprit. Given that one of the benefits of working with B2pin2 is supposed to be its stability towards these issues, the authors reported going the extra mile and finding that the bad bottle of B2pin2 had actually degraded into HOBpin, almost quantitatively. 

Having an entire bottle decomp is somewhat unusual, so the authors went even further to understand- how does this happen? What does this mean for its reactivity in borylation reactions? 

How it works:

The first step was to figure out under what conditions B2pin2 begins to fall apart. 

The obvious thing to do was to set a bottle of B2pin2 out on the shelf, just like normal, but check on it every so often and try to quantify the decomposition. (I am sure this was not the graduate students' only project). 

Eventually they got tired of this and tried heating the solid B2pin2 at 50 C until it fell apart, which took about 3 days until they started seeing some HO-Bpin or (Bpin)2O, and then by 10 days in the bottle was completely dead. 

The obvious culprits for the presence of the oxygen or hydrogen atoms in the products are air and water, so the next step was to identify which was the main culprit. While nothing happened in an atmosphere with "dry" O2, in an atmosphere of "moistened O2", which means under O2 with small but present quantity of water vapor, degradation was quickly observed. Interestingly, the water could be replaced by a small quantity of HO-Bpin, suggesting the role water is playing might be catalytic. 

 

I'm going to skip from here straight to the proposed mechanism, then walk through how they came to this conclusion:

 

The authors determined that B2pin2 (or other diborane species) are able to bind water or other alcohols. Using various equivalents of molten menthol, the authors were able to observe changes in the NMR spectra proportional (albeit not directly) to the ratio of diborane : menthol. This is called the method of continuous variation, or a Job plot. The key finding was that while this binding does occur, the degradation is not caused by high Lewis acidity of B2pin2- it is less Lewis acidic than B2cat2 or other diborane species. 

Next, the rate limiting step  involves O2. The authors did a very clever KIE experiment, using deuterated menthol, and showed massive differences in KIE depending on if the sample had been stored in air (so O2 was present in the crystal lattice) or in N2 (so no O2 is present in the lattice). 

The authors determined this step must occur in a highly ordered transition state by calculating ΔS‡ from the Arrhenius equation. By collecting kinetic data at different temperatures, the authors could then calculate the activation energy, and from there calculate ΔS‡, ΔH‡, and ΔG‡. The authors observed a large negative ΔS‡, meaning entropy decreases in the transition state, requiring a greater degree of structure.

 

Additionally, the authors acquired rate data at different concentrations to determine the order of the reaction with respect to B2pin2. Interestingly, there appear to be two different rate orders, depending on the concentration of B2pin (note the inflection point)

 

Based on this, the authors suggest the possibility of cyclic or dimeric transition states, which it makes sense would be highly ordered.  

Taking all this together, the decomposition of B2pin2 is mediated by O2 and catalyzed by an initial quantity of H2O. However, once a little bit of H2O gets in, then the degradation product HOBpin is able to further catalyze decomposition, leading to the eventual (and rapid) decomposition of the entire bottle. This explains why bottles may remain fine for a long time (especially if unopened), but then mysteriously completely fail. 

The authors have a series of great conclusions about the utility of this method, which I won't reproduce here (go read the paper!)

Initial Questions and Key Findings

1. Is B2pin2 prone to decomposition with air?

A. Yes, B2pin2 has been shown to decompose when mixed with O2 and trace H2O, which heat rapidly hastens. While mixing B2pin2 with just O2 and no H2O doesn't lead to decomposition, Earth's atmosphere does have enough water vapor to lead to eventual degradation. 

2. Does this decomposition happen slowly over time?

A. Not really- once decomposition start, it auto-accelerates. This means that a bottle that was good enough for 10 months may not be fine at 11 months- once decomposition happens, the bottle quickly becomes useless.  

3. How do you stop B2pin2 from decomposing?

A. Keep it away from oxygen and water! Now that the decomposition pathway and products are known, and that they require O2, if you store your B2pin2 in a glovebox rather than the cabinet, it shouldn't degrade. I will note that the authors did not discuss storage in a dessicator- I would have loved to see if B2pin2 degrades at 50 C when kept over calcium sulfate, which should ideally give the anhydrous O2 environment that B2pin2 appeared stable in. 

Takeaways

Don't store your B2pin2 in a cabinet if you're going to use it repeatedly over a period of time! If you keep opening and closing the bottle, that introduces air and moisture that will lead to its degradation.