Enamine Double-Take

When I have a few minutes of down time at work, I like to flip through the most recent issue of C&EN.  Granted, it's been a busy summer, so I'm a few issues behind; I just cracked the cover of the July 29, 2013 issue today!

As I flipped through, an interesting-looking story covering fluorinated pyrrolidines caught my eye.
But wait, something's wrong here. Did you catch it?

Source: Enamine / C&EN July 29, 2013, p. 12

It just looks like a story! Someone clever over at the company matched the C&EN font, style, and text layout to camouflage their ad as a real story!

Well played, Enamine.

Coaching Science

Scrolling through my ACS Matters newsletter, I came across an interesting program I hadn't seen before:


The ACS Science Coach Program.

Participants in the program volunteer with a local elementary, middle, or high school, visiting at least six (6)
times, helping to plan labs and mentor young scientists. ACS even chips in a small grant ($500) to support the effort. Sounds like a cool program to me!

Just one question: Do you suppose the admins ever read the #ChemCoach carnival? [crosses fingers]

Update: Apparently, this dates back to pre-2011, so perhaps *I* subconsciously used *their* idea!

Valleytronics? More 'Borrowed' Phrasing...

Update: 8/9/13: Editors respond...

@SeeArrOh Thank you so much for this. We have taken notice, and we will act as soon as possible. @NatureNano
— Nature Materials (@NatureMaterials) August 9, 2013

***

Tonight must be "Twitter tipster" and "authors behaving badly" night!

From the 'News & Views' pages of two vaunted Nature publishing journals come the latest chunks of potentially plagiarized text. Please open your browsers to this 2012 Nature Nanotech article, and then this 2013 Nature Materials piece. Now, I'm not going to pretend I'm a p-chem or 'valleytronics' expert, but I can certainly spot duped text on command:

NN paragraph 2:

"Electrons travel through a crystal as waves, which are described by a momentum (which is a continuous variable) and a spin (which is a discrete index). It is possible for a crystal to have two or more crystal axes that differ in their orientation, but are otherwise identical: such axes can support electron waves that are also identical apart from their direction (or, more precisely, their momentum)."

NM paragraph 2:

"Electrons travel through a crystal as waves, which are described by a momentum (which is a continuous variable) and a spin (which is a discrete index). It is possible for a crystal to have two or more crystal axes that differ in their orientation, but are otherwise identical: such axes can support electron waves that are also identical apart from their direction (or, more precisely, their momentum)."

Missed the changes? There are none; this is lifted word-for-word.

Another, perhaps?

NN graf 3:

"As in spintronics, there are two main challenges facing researchers trying to make valleytronic devices. The first is restricting electrons to one quantum number, which for valleytronics means localizing them to one momentum valley. This is also referred to as achieving valley polarization. The second challenge is to detect the valley-polarized current."

NM graf 3:

"As in spintronics, there are two main challenges facing researchers trying to make valleytronic devices. The first is restricting electrons to one quantum number, which for valleytronics means localizing them to one momentum valley. This is also referred to as achieving valley polarization. The second challenge is to detect the valley-polarized current."

Hope you didn't blink much, 'cause that one's identical, too.

Although I don't excuse it, I can understand the pressure to grab text under a research deadline, or to emulate a master author. But for news write-ups?!? Looks like someone's got some 'splaining to do...

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.

CPME? New to Me!

While reading through the latest Org. Lett. ASAPs, I came across a slick cross-coupling reported by the Walsh group (UPenn). The reaction unites acetamides and aryl chlorides, helped along by a "hybrid" Buchwald-Kwong pre-catalyst. Neat stuff.

Source: Org. Lett. | Walsh group

A certain passage caught my eye, midway down the second page (emphasis mine):

 "...four common solvents [toluene, cyclopentyl methyl ether (CPME), dioxane, and dimethoxyethane (DME)] were screened..."

All 'common' solvents, even CPME? I don't recall seeing that solvent in Trevor Laird's OPRD piece. Or on several solvent boiling point charts. In fact, I don't think I've ever used it...and I'm doing cross-couplings all day!

A quick literature dig on CPME turned up this OPRD, perhaps its grand introduction to the process scene. Looks like it exhibits several advantages over diethyl ether (higher boiling, lower peroxide formation), and improved safety metrics over dioxane or THF.

Readers: Am I just late to the game? Are process folks everywhere charging liters of CPME into reactors 24/7? Please clue me in.

Open Letter to Recruiters

Dear Biotech Recruiters:

Good morning! It's me, early-to-mid-career synthetic chemist with multiple first-author papers, Ph.D. / post-doc from a Top 10 program, and pharma job experience.

How's things?

I'm a bit worried that my emails and phone calls to you have gone unanswered since we'd last spoken. See, my (tiny) chemistry company could go bust at any moment, and I'd really like to have one of your jobs in my back pocket, y'know, just in case...

I'm not entirely sure who you're looking for, but I'm starting to think it's not me. I do apologize for having not been born 10 years earlier, when I could have taken full advantage of the '90s Biotech Boom.

Back then, doctoral degrees only took 4 years, and then you could jump out into a six-figure job designing drugs straightaway - no post-doc required! Project teams swelled up, thus you got listed on more patents and papers, and probably got all sorts of crazy performance incentives. (I won't even bring up stock options and signing bonuses, since they've mostly gone the way of the dodo). Those lucky folks are now eminently qualified, experienced, and well-connected. They're shoo-ins for any job you have listed.

Well, what about me? I'm young, hungry, internet-savvy and have pretty low salary expectations. I don't yet have a family, and I work tons of unpaid overtime.

I feel like I'm playing against a stacked deck, where everyone has Aces and Kings, but I'm stuck with Crazy Eights. Can I ever catch up?

Looking forward to your call,
-SAO

Scalable Ingenol? Phil Strikes Again!

Update: Want the inside scoop? Check out Open Flask!

I'm officially declaring it: Every 6-7 months, we should expect another huge molecule to fall to Phil & Co:

May 2011: Cortistatin
November 2011: Taxane Cores
May 2012: Ten Meroterpenoids.
December 2012: Ouabagenin

July 2013: Seen the latest* over at ScienceExpress? I think this scheme sums the whole thing up quite nicely:

And that's why it's in Science, kids...
Source: Baran Group | ScienceExpress

Ingenol falls! LEO Pharma, in collaboration with Scripps, may soon make gram-scale batches of ingenol analogs - something that used to take entire groups years to make. This paper cheers from so many different bleachers, I can't even count 'em all:

Total synthesis accesses trace plant metabolite!

Investment in basic research reaps huge Pharma dividends!

Imitating nature makes stitching together complex terpenes look easy!

Enzymes, Schmenzymes...

This paper really does have something for everyone. A volatile intermediate gumming up the works. A surprise crystallization. X-Ray structures. Some allenic Pauson-Khand reactions. A low-temp vinylogous pinacol rearrangement. Even some C-H activation / oxidation tossed in at the end.

If you want some more ingenol goodies, head on over to Chemistry World's fantastic write-up.
And, of course, join me on PhilWatch somewhere around January 2014...

*Thanks again to Brandon for a copy.