Big Fish, New Ponds?

Have you kept your ear to the ground? Felt something on the breeze? Getting a "gut feeling"?

The most recent edition of Chemistry Bumper Cars - Faculty Moves, for the uninitiated - leans towards bigger deals and dramatic poaches as the Fall term looms over the Summer horizon. Here's the latest I've heard about, with my own opinion about whether the rumor holds water.

Dave MacMillan to leave Princeton, for...?
Odds: Low

I hear what you're saying: MacMillan has already moved twice (Berkeley -> Caltech -> Princeton), and we're talking about a researcher who averages an award every year and a new named professorship every four. However, he's fairly well settled into a tight relationship with Merck, who are local to NJ. He's also helped propel Princeton back up in the rankings over the past decade. I can think of only one university that sounds like any kind of a step up, and they have plenty of organic power at the moment.

Dirk Trauner to NYU
Odds: Medium

Though I've heard this more than once, I'm scratching my head about how it makes sense for Trauner. Part of his motivation in returning to LMU was to continue the Mulzer mystique: the powerhouse European natural products group that makes densely-functionalized products appear as if by magic. Then again, NYU seems to be aggressively searching for a certain kind of chemist; maybe Dirk is slated to be the new Phil Baran of the East Coast?*

Update: As seen in the comments, Dirk himself confirms. My gracious thanks to the Professor.

Tom Rovis to Columbia
Odds: Certain

Signed, sealed, and delivered to Columbia back in the Spring.

Dave Liu to Broad from Harvard
Odds: Low

First he was an undergraduate wunderkind with Corey, now one of the youngest Full Professors and an HHMI scholar, all before age 40. He's already a core faculty member with Broad while managing his Harvard group, and I see no reason for Harvard (or for Liu) to wish to terminate his current position. This may sound like wild speculation or stargazing, but I fully suspect Liu's name goes on a nomination for a Big Prize within ~5 yrs, and I think Harvard would do everything they could to keep him in the fold for that day.

Update: As noted in the comments, does appear Liu will have to be physically present on the Broad's campus.

Karen Goldberg to leave U. Washington
Odds: Low

I very much want to believe, especially since UW lost Jim Mayer a few years back, that they can retain Goldberg, a C-H activation and general OM superstar. She boasts a local Center and a named professorship, as well as a Department with plenty of talented young blood: Boydston, Bush, Cossairt, Fu, Lalic, Schlenker, Theberge, Zalatan, all hired in just the last 6 years, doubtless some drawn there through her influence. I'm sure she'd succeed at a Caltech or an MIT, but I really don't know enough about her motivations to say any more conclusively.

Greg Verdine leaves Harvard to run companies full-time 
Odds: High

It's said you can throw a rock in Cambridge these days and hit a VC. Seeing how much apparent fun and success Verdine has had with his previous ventures into the private sector, I'm betting he continues this line full-time and slowly winds down managing theses and group meetings.

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*Today's ridiculous statistic: In the past 20 years, Baran and Trauner have authored a combined 372 research papers. That's 2-3 entire careers, and these are guys with 20+ years ahead of them. Damn.

Honoring Carlos Barbas

Carlos F. Barbas III, a synthetic chemistry professor at Scripps, passed away just over a month ago. I remember first reading about his proline-catalyzed aldol reactions early in my graduate career; I assumed he'd one day share a Nobel Prize for organocatalysis.

In Angewandte Chemie, Phil Baran eulogizes Prof. Barbas well. I hadn't known, for example, that he had earned almost 60 patents (!), had founded three companies (Prolifaron, CovX, Zyngenia), and had mentored hundreds of students, all before the age of 50. Unbelievable.

To close, I'll use Prof. Baran's words:

"He had so much to live for and lived life to the fullest when he could.  

He would want all of you to do the same."

Cryptic Retraction, Uncovered

Earlier today, a curious Twitter tipster wondered aloud about an "obtuse retraction notice" in JACS:

"The structure of compound 1, the major compound, of the manuscript was mistakenly assigned. As a result the authors withdraw this manuscript."

You heard it right, folks: An entire (published) manuscript, all down to one set of spectra.

So, what went wrong here? Here's the carbon-13 spectrum, from the SI:

Source: Jang group | JACS 2008

Whoa! That's a lot of carbons for that relatively simple product. I count 39 signals, aside from solvent, despite the compound's formula - and the authors' peak lists - only accounting for 26.

Another tweet (thanks, Neil!) clued me in to this Organometallics paper, in which they prepare the same compound. Compare the spectrum above to this one:

Source: Hor group | Organometallics 2011

I count 26 major signals, about as many as should be there, given the slight magnetic inequivalency of the benzyl carbons.

So, what went wrong? One clue might be solvent; the first spectrum's taken in a highly polar solvent (d6-acetone), whereas #2 uses ol' NMR stand-by deuterated chloroform. Given the highly polar nature of the first compound, along with the extra signals (and perhaps a second benzyl group in the proton NMR), I'm guessing that spectrum #1 actually shows a quaternary ammonium salt, which might result from "over-benzylation" of the cinchonine starting material.

The real bummer here? I've looked through the rest of the SI, and most compounds appear spot on.

Certainly, the authors managed to perform a challenging radical addition with high selectivity. Even more curiously, the ammonium salt used to effect the transformation (1a) looks correct!

Tough pill to swallow. Kudos to the authors for making the right (tough) choice here, voluntary or not.

Update, 8/8/13: Over at Reddit, stop_chemistry_time has staged a fantastic, ongoing debate with me in the comments. Here's the link.

Cutting-Edge, Nobel-Worthy Chemistry

After all the early fuss about the merits of the 2012 Chemistry Nobel Prize, I noticed this challenge, couched in an earlier Chemjobber comment thread:

"The organic chemists seem to get their hides chapped most easily when a Nobel gets awarded to a 'biologist'. It's worth asking 'what are the fundamental unanswered questions in organic chemistry?'" (Emphasis mine)

Here are three areas, broadly defined, that I believe could win the Chemistry prize next year.

Synthetic trachea
University College London, 2011

1. Whither Polymers?  Darlings of early 20th-century industry, yet they've taken a back burner lately, winning their most recent Nobel in 2000. But, what a decade! Self-healing polymers. Fluoroelastomers you can print into any shape. Synthetic organs, even, grown from biodegradable polymer scaffolds. Trouble with this prize? Picking only three winners...

2. Biochemical Assembly Lines. Yes, cue the "it's not chemistry!" complaints, but I really like work which elucidates the cellular mechanisms plants, animals, and microbes use to assemble huge, medicinally-relevant natural products. Researchers can prompt E. coli to make an antifungal compound, for instance, or yeast to make a cancer therapy. Directed evolution of these assembly proteins, or the DNA which encodes them, can lead to products with wild substitutions and unexpected properties.  Bonus: All the 'big wheels' tend to be card-carrying chemists, and work in chemistry departments. The overarching goal tends to be chemical - utilization of Nature's machinery to produce new compounds.

Usual suspects: Christopher Walsh, Chaitan Khosla, David Liu, Ben Shen.

Walsh Group, JACS 2012

3. Fundamental Catalysis. Technically, there have been a few Nobels for this fairly recently (2001, 2005, 2011). But, what a decade! Here's some currently-exploding fields:

Organocatalysis
Chiral Anion Catalysis
Gold Catalysis
New carbene ligands
Frustrated Lewis pairs
Catalytic C-H activation

Any discipline on this short list could take home a Nobel within 10 years. Admittedly, some of these are rather young, but, as Ash has pointed out, the committee has rewarded ever-shorter publication-to-prize gaps, so it's not without precedent.

Usual Suspects: Dean Toste, Melanie Sanford, Anthony Arduengo, Graham Hutchings, Douglas Stephan, David MacMillan, Benjamin List

Readers, who would you award a Chemistry Nobel?

Hall Pass Top Ten

Apologies for my recent blogging absence. I've been...

1. Trapped in a cargo crate on the high seas, eating bugs and crackers, with only gull cries and typhoons to amuse me. Help!

2. Entering development data into an Excel spreadsheet by hand, from 70 years of targets.

3. Abducted by aliens. I haven't been probed or dissected, but they really, really want me to tell them about organocatalysis and NanoPutians.

11. Messing with the bull, and got the horns.

4. Sleeping (not).

5. Furiously scribbling down every potential idea for a major grant renewal.

6. Stuck in traffic.

7. Eating my way out of a giant cake.

8. Downloading, scanning, printing, "borrowing," recording, and photographing disparate data for a very looooong document.

9. LMAO.

10. Working.

Regular posts [should] resume next week. Stay tuned!

(P.S. Cheat sheet - Nos. 2, 5, 8, and 11 are pretty much true...)

MacMillan's Latest - Almost Autocatalysis?

There's been a veritable treasure trove of interesting reactions in JACS over the past month. One particular ASAP caught my eye today: the latest SOMO-organocatalysis reaction from the MacMillan group at Princeton University.

Back up a second, SOMO? Organocatalysis? For those readers normally not nose-first in organic journals, I'll explain a little. SOMO stands for singly-occupied molecular orbital, which means there's radical chemistry afoot! The initial intermediate in many of these reactions, an enamine, reacts with a single-electron oxidant to form a radical cation, which functions as a sort of chiral radical nucleophile...a rare duck.

Future Organocatalyst?
Pyrrolidine Power!

Organocatalysis utilizes small molecules - amines, urea derivatives, hydrogen-bond donors, or small peptides - to accelerate chemical reactions. MacMillan himself gives a good short course on the topic. Organocatalysis bridges the synthetic and biochemical worlds, adapting Nature's enzymatic tricks into new reactivity.

So, why highlight this reaction? Ever since the Soai reaction, a zinc-catalyzed alkylation first reported in 1995, chemists have been enthralled with autocatalysis, the idea that the product of a given reaction could serve as its own catalyst. In theory, you could start with a tiny bit of an (almost) racemic catalyst, and wind up with a fast, highly selective reaction.

Note the similarity between the catalyst (a pyrrolidinone) and the product (a pyrrolidine). Clip off the nosyl protecting group, and I'd believe that product capable of catalyzing its own formation. Now, I'm not usually a betting person, but I like to look skeptically for what's not mentioned. In this case, only two of the products exhibit the same 2,5 substitution as the catalysts, and the authors mention catalyst development only indirectly. 


I'll offer anyone 3:1 odds that, in the next year, an autocatalytic version of this reaction pops up.