Better Than Word of Mouth

Hello, dear readers. It's been...a while. I promise the blog is not dead, just sleeping for now. My 2017 New Year's resolutions include sculpting specific time out for all the sci-writing goodness. Stay tuned.

Enough maudlin overtures. Now, on to the fun!

Strem has, as any synthetic guru would attest, the highest-quality metal precursors in the biz.* Now, you could spend a weekend cracking ampoules to find out, or just open to the Supporting Information of one of Jeff Bode's recent publications in Org. Lett. Perhaps you remember this reaction - SnAP synthesis of saturated heterocycles - best from a cheeky Derek Lowe tweet:

That's in reference to the stoichiometric incorporation of tin** in the reagent, which serves as a linchpin for the eventual transmetalation to a copper species and ring closure, neatly without disturbance of the ipso heteroatomic group.

Well, much to my surprise, Prof. Bode has climbed on the recent trend of showing one's work through tactful inclusion of smartphone pics to buoy up procedure adoption. Especially with fussy transition metals, valency, contaminants, poor environment, and a whole host of other factors lead to catalyst poisoning and color changes. In the SnAP case, the litmus test seems to be formation of a correctly ligated Cu(II) ion in lutidine relative to the (probable) hexaaquo cuprate species formed as a blue heterogeneous train wreck.

The kicker? The fairly indiscreet preference for the Strem copper(II) precursor over all other suppliers. Look at the change! Night and day, and key to making these reactions work.

You couldn't buy better advertising than this....right, Strem?
Bravo, Bode group! I look forward to seeing your colorful coupling chemistry in future reads.

--

*Dear Strem: please send non-sequential $50 bills to See Arr Oh at Big City Company, USA
**SnAP. Get it? [drum kit]

Rhodium Gets It Done

Interesting, informative intermediates from Rh(I) silylation

In this week's Science, Hartwig and Cheng disclose some pretty swanky C-H activation chemistry. By combining Rh(I) dimer, a really bulky diphosphine ligand, a cheap, bulky hydrosilane, and a hydrogen "acceptor," the pair turn relatively distant aromatic bonds into highly functional silicon handles. In certain cases, tricks like capping a carbazole with a bulky TIPS group direct the silylation para - all the way to the other side of the aromatic ring!

The authors quickly point out that this silylation runs at "low" temps (80 deg C), uses fairly cheap commercially-available reagents, and occurs with almost reversed selectivity to the corresponding direct borylation conditions. But my favorite part comes from a deep dive into the Supporting Information. Far from the discussion of academic over-publishing we've had for the past few days, Hartwig and Cheng really sculpt a great paper here: Stability studies. Reactivity differences (Si vs. B). Cross-couplings. Preliminary mechanistic details.

As always, there's tons more to do. Getting out of the glovebox with a more stable Rh precursor, or translating the reactivity to an earlier metal (a tall order!). Deeper mechanistic studies would certainly show the way. Even more tantalizing? Using single-enantiomer versions of the bulky ligands to incorporate some chiral-at-silicon synthons. I can't wait to see the rest of this story.

Counterion Conundrum

(For Popkin's great Science News writeup, click here)
(Update - Also, Chemistry World!)

Update (11/13/13) - Blog buddy Lila Guterman of Science News has the inside scoop:
"An answer! Authors via @gabrielpopkin: cerium(III)chloride heptahydrate (99.9% pure) from Sigma (cat. nr. 228931-25G)"

~~

Fascinating news for the inorganic biochemistry fans out there: Scientists have ID'd a bacterium (Methylacidiphilum fumariolicum) living in highly acidic volcanic pools that seems to use rare earth metals in one of its enzymes. A multinational team modeled the enzyme with a variety of rare earth cores, and the bacterium appeared to selectively take them up in cell culture. Cool!

Just one small problem: What's the counterion?!?

My crack online reporting team has scoured the manuscript, finding only mentions of a mysterious Ce(III), along with triply-oxidized La* and Pr. Nowhere in the Supporting Information do they mention reagents used, and the reporter has confirmed that this subject wasn't broached.

Given the other salts the researchers added to the media, it's likely that they used either cerium (III) sulfate or cerium (III) chloride. However, Sigma-Aldrich sells no less than 10 different cerium (III) salts (Strem has over 20!), and I'm willing to bet they have markedly different bioavailability, oxidation potential, aqueous solubility...the works.

Readers, does anyone know what the cerium source is in this paper?** I certainly don't wish to draw unwarranted conclusions, but we're all still touchy over another recent dust-up having to do with a miraculous trace element.

Please let me know in the comments.

*IUPAC police: Throughout the paper, the authors refer to "Ln ions." Do you suppose they mean La (lanthanum)? Are elements abbreviated differently in other places?

**Interestingly, the authors note that their acidic growth media leached trace rare earths out of the glassware. I've never looked at that as a reaction contaminant, but I guess I'll have to start!

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.

Friday Fun: How to Fund Your Data Analyst

Remember Amos Smith's Editorial, discussed here yesterday?

(and here, and here, and here)

I wondered, on Twitter: How many submissions does Organic Letters get in a year, anyway?

Sonja Krane, a JACS editor, set me straight:

@seearroh Journal submission statistics aren't publicly available. Sorry I can't be more helpful in this case!
— Sonja Krane (@sonjakrane) June 6, 2013

Rats, foiled again! But then, an interesting tidbit from Stu Cantrill over at Nature Chemistry
(N.B. Stu used to work at OL):

@seearroh When I was there, accept rate was getting down to 50%. I suspect now 30-40%, so look at papers published in 2012 & go from there.
— Stuart Cantrill (@stuartcantrill) June 7, 2013 

Hmm, so all I have to do is count. In 2012, Organic Letters published 24 issues, which seem to have an average article count ~80 / per.* So that's 2,000 articles / year, give or take 100. Now, let's assume Stu's lower range (30% acceptance) - that's 7,000 submissions. Back of the envelope, I'd guess an average Supporting Info section to clock in at around 40 pages nowadays.

That's 280,000 pages of SI.
Pity the poor Data Analyst.

But...what a great way to FUND this potentially burgeoning "alternative" career! A nominal fee of, say, $0.10 / SI page - price of a photocopy from way back, kids - would immediately bring $30K into the journal's coffers. A $3 "data verification" fee per manuscript brings another $21K. Not big money, but we're now into the realm of serious subsidy for someone's salary.


Readers: Would you pay $7.00 to submit your OL manuscript?

* [(Dec 21 + July 6 + Jan 6 + Apr 20) - (corrections + editorials)] = 318 articles / 4 = 79.5