I was interested to see a recent paper in Organic Letters on a class of compounds I’d never seen before: 1,2-dihydro-1,2-azaborines. There’s the structure, in case that doesn’t immediately call something to mind.
These things, which are isoelectronic with benzene, were made by the Liu group at Oregon. Their method (ring-closing metathesis) for making them seems superior to the rather sparse techniques that have been available up until now, and they’ve prepared a number of useful and interesting intermediates. They’re rather stable – even the B-H compound with an N-ethyl group, the simplest in the paper, can be run down a silica gel column. An X-ray structure shows that the ring is indeed flat, and it seems to be aromatic and delocalized.
So. . .what I’d like to know is, who’s going to be the first person wild-eyed enough to put this in a drug candidate structure? Boron has a bad reputation (“boron for morons”, as they say), but hey, Millennium is out there making money with Velcade, a boronic acid. I have absolutely no idea what the fate of this heterocycle is in vivo, what its toxicity might be or what it gets metabolized to (if anything). And neither do you, nor does anyone. Let’s find out!
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One For the Brave
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