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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: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

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August 22, 2012

More Boronic Esters, Please

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Posted by Derek

Here's the Suzuki reaction taken down about as far as it can go: two boron groups on one carbon.
diboron.png
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


COMMENTS

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

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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.

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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

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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.

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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.

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

recent and elegant synthesis of triarylmethanes by C-H functionalization:
10.1021/ja3047816

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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: http://dx.doi.org/10.1016/S0022-328X(00)80082-0

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!

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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.

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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.

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