About this Author
DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

Chemistry and Drug Data: Drugbank
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
Not Voodoo

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
Realizations in Biostatistics
ChemSpider Blog
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Eye on FDA
Chemical Forums
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa

Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
Gene Expression (I)
Gene Expression (II)
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net

Medical Blogs
DB's Medical Rants
Science-Based Medicine
Respectful Insolence
Diabetes Mine

Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem

Politics / Current Events
Virginia Postrel
Belmont Club
Mickey Kaus

Belles Lettres
Uncouth Reflections
Arts and Letters Daily
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« Watch that Little Letter "c" | Main | More on Pharma Stock Buybacks »

August 22, 2012

More Boronic Esters, Please

Email This Entry

Posted by Derek

Here's the Suzuki reaction taken down about as far as it can go: two boron groups on one carbon.
I didn't even know that you could make those things - no doubt someone will be inspired to try the three-boron version next. Diarylmethanes aren't the most preferred drug structures in the world (that carbon is just waiting to be oxidized), but I can't say that I've always avoided them on those grounds. I was on a project where we made a whole series of the things, actually - didn't work out so well for the intended target, but the compounds went on to hit in a completely different assay, so the company did probably get its money's worth.

Comments (11) + TrackBacks (0) | Category: Chemical News


1. milkshake on August 22, 2012 12:25 PM writes...

this could be quite nice for making benzyl alcohols and aldehydes from sensitive aryl halides

Permalink to Comment

2. heresjonny on August 22, 2012 2:47 PM writes...

would be great if they can make those work with the difluoromethylene instead of the methylene.

Permalink to Comment

3. Flatland on August 22, 2012 6:20 PM writes...

I suppose it might be possible to extend to difluoromethylene, with modification (ditch the lithium for zinc perhaps).

As an aside, the original report for the synthesis of the diborylmethane is hilarious in its own right: Castle, R. B.; Matteson, D. S. J. Organometal. Chem. 1969, 20, 19

Permalink to Comment

4. Rhenium on August 22, 2012 7:04 PM writes...

#3: I see what you mean...

"In one instance, all the lithium appeared to have reacted and the mixture was left at room temperature, but a subsequent exothermic reaction led to vigorous refluxing, separation of a ground-joint connection, and spontaneous ignition
of the mixture on contact with air."

Permalink to Comment

5. Flatland on August 22, 2012 7:58 PM writes...

#4: I got as far as:

"Subsequent experience has indicated that every one of these choices except the solvent was wrong, each sufficiently so to spoil the result by itseIf, and it is no wonder that intractable tar resulted."

That's a level of honesty and levity that the more literature needs.

Permalink to Comment

6. Vinod Jairaj on August 22, 2012 11:56 PM writes...

As # 2 says, it will be interesting with the difluoromethylene group. The reactivity / stability would be something to look out for. #3: I totally agree with your first statement - ditch the lithium for zinc. I have worked a lot on organofluorine compounds. We have generated fluorinated zinc and cadmium reagents at room temperature. They are stable, with minimal loss of activity, as long as they are stored in an inert atmosphere.

Permalink to Comment

7. InfMP on August 23, 2012 10:56 AM writes...

recent and elegant synthesis of triarylmethanes by C-H functionalization:

Permalink to Comment

8. Canageek on August 23, 2012 12:15 PM writes...

This reaction also looked rather useful to my lab, so I looked up how to make them. The link for anyone else who wants it instead of going through the citation provided by Flatland:

Permalink to Comment

9. Canageek on August 23, 2012 12:18 PM writes...

Wait. What? I had my first doubletake while reading the abstract:

">100 g batches by the reaction of dimethoxyboron chloride and carbon tetrachloride with lithium in tetrahydrofuran."

So....first. 100 g scale? That is....unusual. The second: Carbon tet? Ok, I can see it used as a starting material, just want to keep it well within the fumehood. My grandfather washed his lab with it every day, I can work with it. Of course, he also died of lung disease...

At this rate I'm surprised he was using lithium, and not something further down the periodic table!

Permalink to Comment

10. Canageek on August 23, 2012 12:33 PM writes...

A final note: That original paper actually already made the 3 and 4 substituted versions, along with many others.

Permalink to Comment

11. Dr. J on September 9, 2012 7:33 PM writes...

#2 (heresjonny)/#3 Flatland: Sounds like a reasonable idea, possibly a fundable research idea! I'm sure someone will jump on that eventually, and I'll be looking for it.

Permalink to Comment


Remember Me?


Email this entry to:

Your email address:

Message (optional):

The Last Post
The GSK Layoffs Continue, By Proxy
The Move is Nigh
Another Alzheimer's IPO
Cutbacks at C&E News
Sanofi Pays to Get Back Into Oncology
An Irresponsible Statement About Curing Cancer
Oliver Sacks on Turning Back to Chemistry