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January 3, 2007
You'll Be Safe Under Here. Maybe.
Posted by Derek
I see that there's a new edition
of the book that organic chemists just call "Greene"; otherwise known as "Protective Groups in Organic Synthesis". This is the fourth, and I'm of an age to remember the first one back in about 1981, when I was still an undergraduate. The new volume could swallow the old one whole - it must be five times the length. Back then the book had some competition, but now it has none at all.
For the non-chemists in the crowd, a protecting group is the molecular equivalent of masking tape. It's a temporary group that you tack on to some reactive part of a molecule to keep it from messing things up while you work on the rest. Ideally, this would be something totally selective for the functionality you're trying to protect, which goes on easily and comes off just as lightly without affecting anything else. Oh, and it has to stand up to every other kind of reaction known to science along the way. That protecting group does not yet exist, or if it does, no one's told me about it. But there are some pretty decent ones, depending on what you're asking them to put up with before their removal.
Everyone who does organic synthesis has to use these things at some point. Because I did carbohydrate-based synthesis in my grad school work (all those hydroxyl groups), I had to use the things constantly, and the trick was to keep them straight and removable in each other's presence. But it's safe to say that no one likes using them. There's a persistent feeling of. . .well, inelegance that attaches to them, no matter how nifty the conditions used to apply and remove them. After all, that's two more steps added to your synthesis, and two which more or less cancel each other out after all that work.
You can't help but think that really advanced organic chemistry will find a way around such problems. We aren't there. For now, it's duct-taped umbrellas, cement-spotted plastic domes, and jammed-on crash helmets for our molecules, and not much we can do about it. Greene's book has all the ugly but necessary details anyone needs.
Comments (12)
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1. milkshake on January 3, 2007 10:40 PM writes...
Nature is not very atom-economic in its choice of substrates and reagents either, it is just better at recycling the leftovers.
Protecting groups can turn a hygroscopic goo into a well-behaved crystalline material that you can actually purify - it is not just necessary evil, the protecting groups, as you are aware.
When somebody compains about wastefulness of trityl as a protection group (or triphenyl phosphine in Mitsunobu) it is best to reply that atom economy taken to extreme would mean that you could not use any organic solvents in your reactions.
Permalink to Comment2. Chrispy on January 3, 2007 11:30 PM writes...
It seems like people care less about yields than getting their product. It's wasteful but fast.
Permalink to Comment3. Paul on January 4, 2007 12:34 AM writes...
Mr. McGuire: I want to say two words to you. Just two words.
Permalink to CommentBenjamin: Yes, sir.
Mr. McGuire: Are you listening?
Benjamin: Yes, I am.
Mr. McGuire: C-H Activation.
4. MolecularGeek on January 4, 2007 11:16 AM writes...
When somebody compains about wastefulness of trityl as a protection group (or triphenyl phosphine in Mitsunobu) it is best to reply that atom economy taken to extreme would mean that you could not use any organic solvents in your reactions.
The way things are going in some jurisdictions, organic solvents may well be banned in them. And there are a few graduate programs in green chemistry where eliminating them is a hot research topic too.
MG
Permalink to Comment5. s on January 4, 2007 11:57 AM writes...
You don't consider the Kocienski protecting group book competition?
Permalink to Comment6. Srikanth on January 4, 2007 12:05 PM writes...
When say it is inellegant means you think there is elegance? Are you taking the crazy pills Americans chew like pop-corn? Organic chemistry is smelly and dirty. Takes hard work and the end result nobody can see. Since carbohydrate chemistry is nothing but protecting groups it is strange you chose to study that. Fischer did everything a 100 years ago anyway.
Permalink to Comment7. milo on January 4, 2007 12:26 PM writes...
ooh..ooh.. Can I feed the troll?
Permalink to Comment8. Ed Vawter on January 4, 2007 4:12 PM writes...
I have both Greene's book (3rd ed) and Kocienski's book on my desk. While Kocienski's book is good, it is far from comprehensive. Kocienski's book is only 260 pages whereas Greene's book is 779 (3rd edition; 4th is 1082 according to Amazon). I bought Kocienski's book since it was more recent than the 3rd edition of Greene's and I figured it would be a few years beofre GReen's was updated (3rd ed is copyright 1999 and the 4th edition is copyright 2006).
I do like the index in Kocienski's group on the inside cover. It allows me to look up grotecting groups very quickly. I usually reach for it first and then refer to Greene's if needed.
I should also mention that you can search within Greene's book on Amazon to see where certain words are mentioned and go directly to a page.
This and Larock's Comprehensove Organic Chemistry and March's Advanced Organic Chemistry are books I could not live without.
While green chemistry and atom economy may in the future rule the day, it is a long ways off and we need references books such as Greene's Protecting Groups until then.
Permalink to Comment9. Jose on January 4, 2007 5:50 PM writes...
Kocienski's protecting group book has always struck me as textbook more than a handbook. It is very, very good at showing the logic and process of planning a nat prod synthesis with serious P.G. issues. However, if you are having a devil of a time finding deprotection conditions that won't nuke aomething else in your substrate, Greene is the only option.
Permalink to Comment10. TNC on January 4, 2007 9:10 PM writes...
Mr. Vawter: What do you use Larock for? Curious to see how others use it on a day to day basis.
What does the 'In the Pipeline' community think about protecting-group free syntheses?
Permalink to Comment11. az on January 5, 2007 6:18 AM writes...
I work in the field of process development, and obviously atom efficiency and pg-free syntheses are the target. But many times protecting groups are the solution to obtain products with the required purity when no crystalline form of an intermediate can be easily obtained, and you work on a neutral molecule that cannot give salts.
Permalink to Comment12. Marvin Barraquias on January 5, 2007 8:29 AM writes...
well everyone is a part of nature...
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