Monday, March 15, 2010

nice drawing

Today as I was perusing the ASAPs, I came upon this one almost immediately:

The graphic looks like there's a lot going on, I like RCM, and they even have an exclamation point in the title! I had to read on!

Anyway, I was immediately greeted with this Scheme:

And the first line threw me a little. It took me a second to figure out what was wrong with it, and all I can say is that it's most likely a hang over from organic chemistry classes. When [3,3]-rearrangements are covered the professors always hammer home the point to look for potential [3,3]-situations whenever there are double bonds present, count to six from the bonds, etc, etc, and then test heavily over the material. In reality, except for groups that use rearrangement chemistry often, [3,3]-rearrangements are no more common than any other reaction, but the automatic counting and checking remain, like a Pavlovian response. I knew something was wrong with the first reaction, but I couldn't put my finger on it.

I actually had to get out pencil and paper and try to do the reaction as drawn, and I couldn't. First I was irked because it's a pet peeve of mine when people flip or rotate molecules to no real gain, like it appears they have done here with the R groups traveling from the left to the right, but that wasn't the biggest problem. I like to think I know some chemistry, but I couldn't get from starting material to product. I read some of the body text finding "The 1,4-diene-ester 9a was prepared by orthoester Claisen rearrangement of the corresponding 1,5-hexadien-3-ol (8a, Aldrich) with catalytic propionic acid or phenol in the case of 8b7 to afford 9b in refluxing triethyl orthoacetate.", while that reinforced the [3,3] business, it provided no more insight as to why this was so hard to figure out, and it conspicuously only mentions one of the two starting materials. I could easily draw a different reaction that provided the product when R = H, but it wouldn't work when R = Me.

I finally went to the supplemental information, and found the starting materials' names: 1,5-hexadien-3-ol, as expected, and 6-methylhepta-1,5-dien-4-ol which I've drawn for you here:

Eagle eyed observers might notice a small difference in the locations of the alcohol groups with respect to the left hand side of the molecules, as drawn, trying to replicate the way 8a,b are drawn in Scheme 2. It's pretty bad that the editors don't catch shit like this, but how do you fuck this stuff up on your own molecules? I understand that they were doing the same reaction multiple times, and most likely wanted to draw both molecules in one to save space, but it seems like it should have been drawn out the long way at least once during all this. Then the later flipping nonsense would be fairly obvious.


Mike said...

Sorry to hi-jack the post, but as long as we are complaining:
I hate those ACIE "highlights" articles. (10.1002/anie.201000479) I saw this today and thought, "Sweet! Another palau'amine synthesis!" only to be disappointed when I saw that it was basically a BOOK REPORT of Baran's synthesis. Can anyone explain to me why this is necessary? Do we really need these? WTF?

scientist 1 said...

That does seem pretty silly, but would it have been better if it was atually another synthesis?

Mike said...

If I was working on that molecule, I wouldn't want to see another synthesis. Since I'm not, however, it would have been a more interesting read had it been another synthesis. I think that I will start writing some of these "highlights" articles to pad my CV. Imagine how awesome that would look (O'Keefe, B. M. "The total synthesis of [some natural product]"...etc.)! Cha-ching!

scientist 1 said...

You could add a picture of you in a smoking jacket in a cushy chair with a glass of wine.

"Let's discuss some molecules ... *sip* ... mmmm, good year."

Jim said...

I wonder if ACIE does that because it knows people want to be told what is important now-a-days or because they promised some gratuitous ass kissing to Baran so he would publish there instead of JACS.

Hurry up and finish kidamycin so I can write a book report on it.

And as for the actual post they just seem to have the R groups on the wrong olefin, and I imagine a lot of people did the same thing I did and thought 'oh, some sort of ortho ester claisen' and moved on without giving it much thought. I bet that's what the reviewers did.

scientist 1 said...

Yup, quality reviewing. A quick skim is all it really needs.

That's one of the things I hate about flipping molecules around. Not only is it more work than not flipping them, but it confuses even the authors as to which side is which.