Friday Fun: Strained Conversation

This graphic was far too funny (to me, anyway) to leave buried in the graphical abstracts...

Courtesy of this Angewandte Chemie paper, in which we learn that "anti-Bredt" olefins - those C=C bonds located at the bridge of a caged bicyclic ring system - don't have to be discarded as possible structures for new natural products. The authors recommend their computational model, which uses modern forcefields to estimate olefin strain (OS) and predict stability of these bridgehead double bonds.

Happy Friday, everyone!

See Arr Oh

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*I know this is a bit belated, but RIP P.v.R. Schleyer. You seemed like a really interesting guy.

Wanted: Chemistry Humorists...err, Editors

Earlier this week, I took Angewandte Chemie to task: their (in)famous graphical abstract puns just weren't funny anymore. They responded with a job opening*, potentially to write exactly those puns I had just maligned. What a coincidence!

.@SeeArrOh A sense of humor is not explicitly mentioned in our recent job advert, but it's clearly a bonus. http://t.co/fSbMb1HMjC #chemjobs

— Angewandte Chemie (@angew_chem) May 4, 2015

Chemistry writers of the world: Are you witty? Good at writing? Want to live in Germany?
Link's embedded in the Tweet.

*Sorry, Chemjobber, I know this is usually your beat, but I really couldn't resist.

Whitesides' Chemical Future

As part of the "Future of Chemistry" essays sponsored by BASF, professor George Whitesides opines in Angewandte Chemie Int'l Edition that chemistry must change in order to keep pace with societal demands and changing scientific landscapes. 

Familiar themes pepper his prose: the tension between "curiosity-driven" and "directed" research, between organizational behavior, motives, and rewards, and several pressing calls to action. After setting some ground rules and introducing us to his main actors - academia, industry, and government - George shifts his essay towards some familiar* grand challenges:

"What is called 'chemistry' now may only be a distant cousin to the chemistry of 50 years from now."

Origin of Life. Informatics. Energy generation, storage, and usage. Cognition. Human augmentation. Death. In twenty-two points, he covers the entire human experience from life to death, from single cells to complex global societies, then leaves himself two outs: numbers 23 ("All the rest") and 24 ("Combinations with adjacent fields").

"Chemistry tends to be excessively modest in its ambitions. Excessive ambition might sometimes be a better strategy."

Hold on for a minute...anyone feel a strange sense of déjà vu? For the past three decades, Whitesides has been in the business of not just inventing the future, but actively predicting it as he goes:

2013: Reinventing Chemistry - RSC Roadshow
2013: Memo to Chemists: Move Away from the Molecule
2013: A Glimpse Into the Future of Diagnostics
2012: Whitesides on Discovery and Development
2011: Whitesides & Deutch on What's Wrong with Academia
2011: Chemistry and the Worm
2010: Towards a Science of Simplicity
2007: Revolutions in Science
2004: Assumptions: Taking Chemistry in New Directions
2001: The Once and Future Nanomachine
1999: Complexity in Chemistry
1995: Holy Grails of Chemistry
1990: What Will Chemistry Do in the Next 20 Years?
1988: Materials for Advanced Electronic Devices - Chemistry for the Future
1986: The Role of Chemistry in Materials Science

Certainly, this essay reads like anything other than a traditional chemistry text. We hear about chemical granfalloons** -- who are synthetic organic chemists, anyway? -- catalytic networks, Facebook and Twitter ("avatars of social engineering"), and even the rather Huxleyan concept of population control. Pasteur's quadrant, aka the choice of research that solves social problems while inventing fundamentally new science, represents for Whitesides the idealized goal, though he admits we're presently much more stuck in the "Liebig apprentice model" of traditional research groups.

Especially resonant for me were the areas Whitesides identifies at collaborative interfaces: megacity logistics and cancer prevention involve far more cooperation along "unfamiliar boundaries" than I had perhaps realized: social, environmental, computational, psychological, and (of course) chemical.

Flying cars - Still not a priority for chemists...yet.
Source: Terrafugia

I found Whitesides' friendly, casual conversation with the reader, breaking down traditional scientific narrative for a personal exchange, rather refreshing. You can actually hear him speaking through the page, his calm, familiar cadence and confident, challenging affect. Recall that George himself has opined often on just how to communicate scientifically; looks like he indeed follows his own presciptions.

I recommend a full read-through for those so inclined. I'll close this meta-review with two points. First, a strong piece of advice from Whitesides' 2007 Priestly Medal address:

"Chemists are the natural leaders for much of the research that needs to be done. But physicists can learn molecular detail, and biologists can learn differential equations. If we do not wish to work on these problems, others certainly do. If it is not our revolution, it will be someone else's."

Finally, Whitesides offers a poignant answer to the age-old stuck-on-an-airplane question: What do chemists do? I won't give away the answer here, but suffice to say it's both more direct and more engaging than how I've traditionally answered. Go have a look.

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*So familiar, in fact, that he references two of his own previous predictive essays. See also, from Philip Ball, here. 
**I'll follow professor Whitesides' daring example of directly citing Wikipedia for this Vonnegut quote.

Strange Cover Art

A small part of me remembers a time before journal articles could all be accessed online. Back then, the cover art -- a creative expression of some of the newly-reported research between the covers -- could swing you towards one journal over another as you milled around the musty library stacks.

Source: Wiley-VCH, c. 2014 / ACIEdoi: 10.1002/anie.201409223

Nowadays, we've lost some of that artistic tradition, save for notable standouts Nature Chemistry and Angewandte Chemie. Hence, my confusion when looking at this week's Angewandte cover art - does anyone understand what's going on here? 

Best I can tell, this graphic is a nod to Prof. Younan Xia's excellent overview of the benefits and risks inherent to nano-scale research. But the graphic appears (to me, anyway) to resemble two angry Pokemon fighting over the sword from Legend of Zelda. About the only chemistry I see? Blink, and you'll miss it: along the blade are five tiny emblems meant to represent common nanostructures such as carbon nanotubes or micelles. 

Readers, am I missing something obvious here, or does this not really communicate the depth of Prof. Xia's review issue?

Déjà vu, LPU

Remember when I posted about the highly-similar cyclobutane insertion chemistry coming out of the Cramer group? Well, a new contestant has just been published in ACIEE:

Source: Cramer, ACIEE 2014

I jumped down the rabbit-hole of the Supporting Information, and returned with these two "general" procedures - blink, and you'll miss the differences!

Source: Cramer et. al., ACIEE 2014, February

Source: Cramer et. al., ACIEE, 2014, July

Same catalyst precursor. Same ligand (well, different enantiomer). Same solvent. Same time. Similar reaction temps and purification conditions. Now, I'm not saying that the Cramer group shouldn't have published this paper, but in the same journal? With essentially the same substrates?

Does anyone else believe that these could have been published together, in a single high-impact paper?

Many Happy Returns

From the ASAPs over at Angewandte Chemie comes this friendly bit of recognition, from mentor to former student:

That has to be the youngest Festschrift I've ever seen...readers?

Doubt

(Reference: JLC1, JLC2, Derek1, Derek2)

Since February 2014, Prof. Tohru Fukuyama's group has issued corrections to 11 published papers in three journals: Angewandte Chemie, Journal of the American Chemical Society, and Organic Letters. Fukuyama's former colleague, Dr. Satoshi Yokoshima (now at Nagoya U), appears as a co-author on 10 of the 11 papers.

Chemical and Engineering News intrepid reporter Beth Halford recently interviewed the two men regarding their ongoing "Correction Crisis." Readers reacted skeptically:

.@cenmag 's Bethany Halford interviews Prof. Fukuyama about NMR spectra issues. Do you buy it? http://t.co/NMvzkofYmW
— Unstable Isotope (@UnstableIsotope) April 12, 2014

[Sigh]...No, I don't.

Let's look at a few more recent correction scandals. After the Cossy group published some strange spectra, Prof. Cossy wrote a letter to the entire Organic Letters community, saying:

"I reach out here with the hope that all readers might learn from this experience as I certainly have. From now on, I will never let a student or postdoc from my group upload a manuscript and/or Supporting Information file to a journal submission site by themselves"

Succinct, supportive, reflective. Prof. Cossy even allowed the responsible lab member to speak through her, saying "I know my behavior is highly unethical. I am deeply sorry for what I have done."

When the Dorta group published a strange statement in the body of their Supporting Information, Dorta spoke to Organometallics Editor John Gladysz, claiming "...the statement [in the SI] was inappropriate." To my knowledge, Prof. Dorta has never blamed his student coauthor, Emma.

Now, let's take a look at the C&EN article. How do Fukuyama and Yokoshima address their spate of corrections?

“Almost all of our recent research accomplishments are the results of close collaboration between myself, Professor Yokoshima, and our students,” Fukuyama explains.

Team spirit! OK, I'm fine with that. Next? (emphasis mine):

“My impression is that some of my students who deleted minor peaks did not take seriously the idea that the spectroscopic data are important proof of the compounds’ purity,” Fukuyama says. “I myself have never manipulated the spectroscopic data or even dreamed that my students would do such a stupid thing.”

Wow. Did they just throw every one of their 19 coauthors (I counted!) under the bus?
Another (emphasis mine):

“It was our fault not to scrutinize every spectrum in the supporting information before sending them out for publication,” Fukuyama adds, “but my staff members and I simply believed that all of my students are honest.” As soon as they learned of the manipulations, he says, “we told our students never to do such a stupid thing. I can assure you that we will never send out manuscripts containing manipulated spectra again.”

To paraphrase the Bard - the Professor doth protest too much, methinks.

Note the "Yes, but..." structure of his argument. See how it lobs the blame squarely back on the coauthors? And the choice of language, calling one's apprentices "stupid" and essentially dishonest? Not cool.

In most scientific organizations, culture comes from the top. Even coauthor Yokoshima admits that...

“We have told our students that the NMR spectra should not contain peaks of residual solvents or impurities for publication...our comments and the limited machine time seemed to have forced them to use the ‘Delete Peak’ function.”

If your group focuses on "clean up your spectra" more than "purify your compounds better," that's a communications issue. If a professor with a large group sees nothing but perfect spectra all day, two thoughts should crop up:

1. "I must have the smartest, most efficient students in the world," or...
2. "Something's fishy here."

Even the busiest profs in the biz - traveling for international conferences, serving on NIH panels, consulting - must still see their students' work at least three times prior to publication. Group meetings, one-on-one office meetings, project round-tables, manuscript submission, reviews, galley proofs? All perfect opportunities to catch ethical errors privately before revealing them to the wider world.

Sadly, the professors don't seem to answer the real question: What went wrong here? Public shaming won't fix your lab's culture. By closing ranks and shutting out 19 potential collaborators, Fukuyama and Yokoshima invite even more scrutiny into their lab's motivations.

Update (4/12/14) - Changed the last paragraph to avoid any judgment on the interview style. I believe Ms. Halford conducted it just fine.

Gold Steps Up

Update, 4/5/14: On Twitter, Yunus chimes in to recommend this Hashmi paper, showing a mononuclear Au(I) catalyst - with crazy adamantyl appendages - that gets down to 0.0001% loading!

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Catalyst: A substance that increases the rate of a reaction without modifying the overall standard Gibbs energy change in the reaction (IUPAC Gold Book).

Though most chemists agree on the above definition, there have always been two camps: "Academic" catalysis (1-20 mol%, 5-100 turnovers), and "Industrial" Catalysis (<0.01 mol%, >10,000 turnovers). As more researchers seek to translate early discoveries into efficient, "green" processes, the desire for robust organometallic species has skyrocketed.

Right now, a few such homogeneous catalysts have made the jump: the Grela Ru metathesis catalysts (0.001%), copper catalysts for boron addition (0.005%), and some iridium and palladium species.

Gerald Hammond and Bo Xu (Louisville) want to add one more to the list: a highly-stable gold catalyst. Their new catalyst, dubbed "BisPhePhosXD-AuCl" (Phew!), takes development lessons from Buchwald (electron-rich, C-to-metal bond) and Widenhoefer (steric bulk to discourage off-cycle species). 

Now here's the fun part: the authors run several typical gold-catalyzed reactions side-by-side with their improved catalyst. In most cases, they're able to shave off 99.9% of the catalyst loading, with comparable yields. Granted, certain reactions take more time with this approach, but a few finish ahead of their literature counterparts. Wow.

Aldrich sells the precatalyst, if you're itching to try it yourself. I'll be very interested to see the next generation of bulked-up ligands, and whether this reactivity transfers over to other precious metals, namely platinum, iridium, or rhodium.

The Lion in Winter

Source: ACIEE | Karen Ostertag

Carl Djerassi + Jeffrey Seeman + Angewandte Chemie
= Must-read material.

Just when you thought you couldn't get enough of Carl's 90th birthday festivities, a new collection of personal quotes has appeared online this week. Djerassi - chemist / author / poet / provocateur - does not disappoint. For the more chemically-inclined, it's full of "Didja know?" moments - for instance, Woodward, Djerassi, and Tishler all submitted syntheses of cortisone to JACS within 3 weeks of each other!

The bulk of the text explores Djerassi's feisty, garrulous backlog of quotables. Here's just a sampling:

On his stamp: "Since 2005, people in Austria - by now thousands - have been licking the back of my head"

On publication: "You owe it to the students and those who collaborate with you...you persuaded them to do it, and obviously at the time that it was worth doing. Presumably, if they completed it, it was good enough to be published."

On community: "Scientists operate within a tribal culture whose rules, mores and quirks generally not communicated through specific lectures and books, but rather are acquired through a form of intellectual osmosis in a mentor-disciple relationship"

The rest run the gamut from social movements (performance-enhancing drugs, the Pill, sex, schadenfreude) to deeply personal hurts (professional exclusion, his daughter's suicide), and end on a peaceful, affirming story concerning the motto of the Djerassi ranch (SMIP, but I won't spoil the secret...)

Give it a read, it's worth every minute.

Cyclobutanone Déjà vu

Didn't I just see that reaction? [rubs eyes]

From the laboratory of Prof. Nicolai Cramer (EPF Lausanne) comes some really neat examples of cyclobutanone C-C activation. Just mix with ~2 mol% of cationic Rh(I), and presto! Out comes a [3.1.2] bicyclo product reminiscent of several neuroactive natural products.

Oftentimes, a catalytic reaction will go gangbusters, but will stubbornly refuse all attempts at asymmetric induction. Apparently not so here - Cramer reports the asymmetric version in ACIEE about two weeks after the initial Organometallics report!

Angew. Chem. Int. Ed. 2014, ASAP

Organometallics 2014, ASAP

Honestly, I might never have noticed, except the TOC graphics for both are nearly identical: a comic pair of orange scissors "snipping" apart the cyclobutanone ring.

So, readers, what's your take? Can't wait to see this reaction applied to a challenging target? Or, a strange choice of synthetic "least publishable units" (LPUs)?

"Crystalline" CO - Saccharin's New Trick

Seems I'm posting an awful lot about artificial sweeteners these days!

This latest example, from the always entertaining and informative folks at Angewandte Chemie, employs our old friend N-formylsaccharin* as a carbon monoxide "equivalent" for Pd-catalyzed addition reactions:

Credit: Manabe Group | ACIEE

Quite a few benefits accrue: No pressure equipment. 'Medium' heat. Relatively low catalyst loading.  Cheap, off-shelf reagents. If they could figure out a slightly less exotic reductant, I'd use this all the time!

So, how does it work, anyway? The researchers confirm CO release by treating formylsaccharin with several bases and observing CO evolution.** The standard (boring) formylation model might be operative here - Pd oxidative addition, CO insertion, reductive cleavage (rinse, repeat). 

OR (more excitingly), the authors note that they detect a transient "acylsaccharin" by HRMS. This might imply that the formylsaccharin reacts directly with the palladated arene, or that the sodium saccharine byproduct plays a role in stabilizing / promoting reduction of the insertion intermediate.

Sweet.

*OK, so it's not saccharin itself, but pretty darn close. First developed by Cossy in 2011 for formylating amines.
**A great mechanism for those looking for cume questions!

Hawker's Talk Secrets

"My Chemical Romance Calls it Quits"
"My Chemical Romance, In Memoriam"
"My Chemical Romance Break Up"

Never fear, dear readers: My 'chemical romance' continues unabated...[rimshot]

At the risk of sounding like a lounge act, I realize that clear communication supports good relationships. So, apparently, does Craig Hawker, an accomplished polymer scientist at UCSB. I've seen him present a few times; the man gives one hell of a talk!

This month, he shares his secrets with you courtesy of a (free!) Angewandte Chemie editorial. Building off the success of Whitesides' essay "Writing a Paper", Hawker points out a crucial difference:

"While a publication can be read again and again, a presentation is over immediately. Therefore, the rules for writing a publication differ from those for preparing a presentation."

Amen! We've all attended deadly discourse disasters: The 9AM conference sleeper. The 4PM no coffee, no snack, sotto voce speaker with tiny font. The don't-stop-for-questions local section dinner meeting. All tragic wastes of opportunity.

"Chemistry? Chemistry? Chemistry? Chemistry?"
Source: Ferris Bueller's Day Off

So, how can we improve?

Hawker offers several simple pointers, divvied up into two major sections ("The Slides" and "The Talk"). For slides, he argues clarity, simplification, and increasing "signal-to-noise" improves the amount of useful information instilled in the audience.

For speech, Hawker advocates skills that would play well in any concert hall: Practice. Engage with the audience, which includes eye contact and interaction. Project confidence. Modulate your voice, and know when to make use of silence.

Most importantly, argues Hawker, we must solicit active feedback. Like late NYC mayor Ed Koch, ask your audience "How'm I doin'?" An honest answer here may sting, but will help you to improve for next time.

Friday Fun - Puns in Native Tongues

Finally! For those chemists who just can't get into a scientific paper without a witty one-liner, Angewandte Chemie delivers. Derek, Excimer, and Chiral Jones noted some of the best (and worst) Angewandte abstract puns over the past 5 years. Hey, any journal that can somehow channel carbene reactions through Britney Spears deserves at least a chuckle.

Well, up to now, most of the puns have been written by the English language editors of the International Edition; regular readers realize that Angewandte publishes a German-language edition as well. Far as I can tell, looking at the 'Early View' tab, they're now translating even the puns ins Deutsch!


From the posted few, we can glimpse some method in the madness. Certain expressions are translated directly, like Goldstandard for "Gold Standard," or Elektrisierende Ergebnisse (Electrifying Results!) for "Electric Results" in English.

A few, however, must not have carried over well enough. "More than LiP service" in English becomes Ein Hauch von Rot (A Touch of Red), and "A gel for all seasons" becomes Ein Gel für alle Fälle (A gel for all cases). The strangest rewrite has to belong to this Fukuyama synthesis of Chartelline C. The reserved German tagline reads Von großen und kleinen Ringen (Of large and small rings), but the English?

"What a core-ker!"

(Must have sounded better in the pub)