E-Birch

Our work on electrochemical Birch reduction was published today. In case you don't want to read the manuscript, here's the Cliff notes:

• Pfizer approached us, saying traditional Birch is bad news for med chemists (alkali metals are spooky; condensing ammonia is gross; the whole thing is a lot of effort). They asked us to make a better Birch.
• We developed some conditions to effect the Birch transformation with electrochem. Basically, the conditions are mix substrate, LiBr, electricity, DMU, a key phosphoramide additive (TPPA), and THF. No ammonia, no alkali metals, no cryogenics.
• Intuitively, one might naively assume that what's going on here is that the LiBr is reduced to Li(0), and from there the reaction goes through a standard chemical Birch mechanism. We assumed that, naively (at first).
• Turns out, that mechanism is not at all the case, as demonstrated by much experimental and computational mechanistic study. Instead, the substrate is reduced directly on the electrode. Further, Li(0) is never generated at all. Safe stuff. Cool beans.
• We went back to Pfizer with this. They seemed pretty happy.
• Oh, also the reaction works in flow, on >100 g scale.
• Oh, also, the key phosphoramide additive, that makes everything work, came from the Li-ion battery literature.

A huge shout-out has to go to our collaborators: Shelley Minteer and her group (led on the student side by postdoc David) for electroanalytical work, Matt Neurock and his group (led on the student side by grad student Sagar) for computational work, and our longtime buddies at Asymchem (led by Longrui) for scaleup and flow work. We should also note that this whole collaboration is driven by the CCI electrochemistry consortium, which has been a tremendous way to put people from various subfields of electrochemistry in touch with one another.

Anyway, normally, this is the part of the blog where we'd tell some funny anecdotes about the project. Unfortunately, the whole team is way too excited to get back in the hood for subsequent projects, so we didn't write anything. In lieu of anecdotes, please accept a few vaguely-electrochemical-Birch-related poems:

Limerick:

We set out to Birch some arenes;
to make a scary reaction more clean.
It turned out lack of lithium
gave us complete freedom
to safely Birch on our Electrosyeeeens

Haiku:

Birch in Winter frost
with Electrochemistry
No lithium, good.

AABBCC:

Poor Arthur Birch
did much research.
He was always sad,
for his reaction was bad.
Now we made it better
but alas, he is deader.

Oh, also we made a video, objectively comparing the time it takes to run a classical, chemical Birch, to the new electrochemical protocol. We hope you enjoy it:

- Electrochemical Birch team