Cornies 2007: Protecting Group of the Year? Seriously?
January 7th, 2008 by excimerHey, first, the lolnano contest got plugged at Wired Science! Yay lolnanos!
Anyway. All of these Cornies on my desk (which are made of solid indium and are mostly responsible for the world’s indium shortage ) are getting in the way of me getting work done, so let’s hand out a few more.
Weird category? Nah, we’re chemists. We rely on protecting groups, and despite what Baran would like, they’ll probably forever have a crucial spot on any organic chemist’s bench. One of the biggest problems with making oligoarenes- long chains of benzene or other aromatic rings- has been the difficulty of synthesizing them. One of the most powerful and useful transformations for making biaryls- the Suzuki reaction- was pretty much out of the question for making compounds with a lot of rings- if you wanted to, you’d have to really go out of your way to do it.
Fortunately, Michinori Suginome’s and Marty Burke’s[1] groups have developed what are basically boronic acid protecting groups- a simple method to iterative Suzuki cross-couplings.
Suginome’s method uses 1,8-diaminonaphthalene as the masking group. It reacts with the boronic acid, after removal of water, to form a diaminoborane, which doesn’t react under anhydrous Suzuki conditions, anhydrous or with water. In particular, it is insensitive to Fu’s modified conditions as well. The protecting group is removed with aqueous acid, and the protection and deprotection are nearly quantitative, as is the coupling.
Burke’s method uses N-methyliminodiacetic acid as the protecting group, which masks the the boron functionality and keeps it from reacting under Buchwald’s anhydrous Suzuki conditions, and the masking group can be removed with mild base. On top of that, workhorses they are, they have also shown the masked boron to be insensitive to lots of different palladium-catalyzed cross-coupling reactions.
Both groups have exploited their new methods to make natural products. Good for them. They get the Corny for developing a simple method en route to the always-interesting (to materialsy folk like us) oligoarenes. Of course, you could have just done away with the boron entirely too… right?
[1] If you think I’m handing this out because he’s got home court advantage… you’re probably right. I never said the Cornies were fair, did I?
Congrats on the Wired Science story!
Mitch
The Suginome 1,8-diaminonaphtalene protecting group looks like a better solution to me – it is stable to aqueous carbonate with heating, the Burke protection needs strictly anhydrous Suzuki condition because it is a mixed anhydride.
The concept is not entirely new: boronic acid tetrahedral complexes with diethanolamine were known already to be nicely-behaved crystalline solids that could be used for isolation of boronic acids and their purification on a silica column. Since the diethanolamine compexes are very unreactive (much less reactive than pinacolate esters) they have to be deprotected before the Suzuki.
Can you make heptaenes with sponge-protected ones?
“insensitive to lots of different palladium-catalyzed cross-coupling reactions.” — wrong DOI under these words, the correct is in the ref. above.
fixed. thanks!
Yeah. It would have been nice to see the sensitivity of the protecting group to other reactions. Burke’s, at least, seems to be insensitive to everything but water.
Burke’s a one callous guy.
Sensitivity to protic basic media is a big deal in Suzuki actually – many protocols do contain water because it helps the reaction.
I’m going to ask a really stupid off-topic question.
The articles in Agenwandte Chemie are exactly the same as those in Agenwandte Chemie International Edition except for the language, right?
yes, and the page number – in original Angew Chem the page number tends to be about 10% higher, German being a somewhat longwordy language. (Thank God there is no Russian edition)
Yeah, scientific Russian is quite ugly – lots of loanwords, which must be put in the right case, gender, number, tense and aspect don’t contribute much to the brevity.
Common words (spoken) are about 25% longer than English.
This is why I dropped Russian after a week in high school.
I had several semesters of Russian. I can barely read it, and couldn’t speak a lick even when I was in the classes. Part of that was just never studying stuff outside science and math, but I always though Russian was a pretty language to hear spoken. I’ve never tried to read anything scientific in Russian.
I’ve read a bunch of translations of Russian mathematicians and physicists. It makes me wish I hadn’t been such a slacker. Nah, not really.
It’s a pretty language, but one I’ll probably never learn. I always did kinda want to be able to read Dostoevsky in his original language, though.
Slavic language are not-so-concise. They are rich on nuances and have absolutely horrific and irregular grammar. You have to learn 14 versions of each noun – they have affixes that change depending on the prepositions. The changes are irregular and depend also on the gender of the noun (each noun is he, she or it, completely unpredictably). You have to memorize it.
On the up side there is only one past, one present and one future tense. All verbs tenses are irregular – plus there are 8 different forms of endings of the verb which signify who causes the action (5 in singular – me, you, he, she, it and 3 in plural mode – we, you, they) which are also pretty irregular and change with the tense also. I forgot to mention each verb comes at least in two similar (but grammatically differing) versions – one describes action that occured only once whereas the other one is for a continuous or repeated action. Oh, and there are few hard-to-pronounced sounds and letters that dont have a counterpart in other languages.
[...] curiosities has awarded the coveted title of Best Protecting Group 2007 to masked boronic acids and champions Marty Burke’s work at Illinois. He used [...]
Solid indium is not actually that solid – indium is a rather soft malleable metal. But it’s low melting point of 158 degrees C makes it a good candidate for home-made trophies I suppose. I used to work in an indium refinery as a Summer job during undergrad. I didn’t know there was a global shortage – I wonder if I still have any “mementos” from those days…
Do you want oligoarenes? You can’t handle oligoarenes! Oligo-1,4-phenylene yourself into a forced planar conjugation frenzy!
10,10-dibromo-9,9-bianthracene plus xs. benzyne into alpha,omega-dibromobitrypticene. Cook it up (fond memories of Tenderbutton) with molten dispersed sodium or free radical whatever to oligomerize. Monobromobitrypticene to control molecular weight distribution by capping. Now… FeCl3/MeNO2 to oxidately couple abutted rings with hydrogen extrusion,
http://www.mazepath.com/uncleal/bitrypt2a.png
condensed dimer, dimerized
http://www.mazepath.com/uncleal/bitrypt2b.png
condensed tetramer; alpha,omega H-termination
Congrats on WIRED! Any route to grant funding advantage is a route to grant funding.
how about Hiyama coupling?
see J. Am. Chem. Soc.. 2007, 129, 11694-11695. DOI: 10.1021/ja074728s
and phenol-triflate strategy?
see Chem. Lett. 2007, 36, 1302-1303. DOI: 10.1246/cl.2007.1302
The Hiyama protocol looks nice- I hadn’t seen that paper before. I can see a few reasons not to use it, such as prepping the organosilane and then protection (when you can just buy boronic acids) and if your stuff is really, really greasy, that group won’t help much in purification. Might be a nice way to make sequential oligoarenes from one building block, but not so much if you have to make several different ones, like burke and suginome did.