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.

Coming Soon: Harvard's ComSciCon

(Thanks to Joseph Meany [@CrimsonAlchemist] for the tip!)

Source: Harvard ComSciCon

Want to study science communication at Harvard? Better hurry!

Applications for the June 2014 ComSciCon ("The Communicating Science workshop for graduate students") close on March 1st. The conference, which opened in 2013, has hosted professional science writers from NPR, The Atlantic, and professors from MIT and Harvard.

The application, which requires a few writing samples and thought exercises, looks pretty straightforward. The best part? This year's conference is open to all science graduate students at US institutions. Successful applicants will receive free registration, travel, and accommodations.

Here's the short version for June:

• Communicating with non-scientific audiences
• Communicating complexity and controversy
• Communicating for a cause
• Communicating with multimedia
• Engaging diverse audiences

Interested? Go apply today. 

Follow ComSciCon on Twitter: @ComSciCon

Coming Soon: Free Online MedChem Course

(Looks like I get the same emails as Chemjobber does!)

Prof. Erland Stevens of Davidson College will be offering an introductory medchem course through EdX:

The seven-week course starts on March 10^th.  Each week has about 1 hour of video and a number of accompanying web pages.

The course is strictly an introduction.  A short syllabus is below.

Week 1 – brief history of medicinal chemistry, introduction to drug development process and regulatory approval

Week 2 – proteins (enzymes and receptors) as drug targets, enzyme inhibition, ligand-receptor binding theory

Week 3 – pharmacokinetics (compartment models, Vd, clearance)

Week 4 – metabolism, phase I, phase II, prodrugs, genetic variability

Week 5 – drug-target complementarity, drugs as part of chemical space, chemical libraries

Week 6 – lead discovery, screening, filtering hits by metrics/structural alerts/predicted PK, SOSA, natural products

Week 7 – lead optimization, functional group replacements, isosteres, directed libraries, peptidomimetics

The overall goal of the course is to get a student up to speed to watch a medicinal chemistry lecture (and maybe even ask a question at the end).

**If anyone signs up and completes this course, I'd love to get their impressions of it for a follow-up post!

Tip of the Iceberg: More Organic Letters Corrections

(Thanks to BRSM for the heads up!)
(Update: See here for Derek's post and thoughts)

Looks like another author just felt the heat of the Data Analyst's gaze. Hot on the heels of the Fukuyama corrections, we have a slate of scrubbed-up 1H spectra from the Nakada group (Waseda University).*

Today's corrections in Org. Lett. ASAP (1, 2, 3, 4, 5) all read rather similarly:

"The 1H NMR spectrum for compound x . . .was found to have been edited to remove solvents and impurities"

Peer-reviewed expert in
Musicology

Syntheses affected include a Taxol fragment, (+)-Colletoic Acid, and Erinacine B. The authors claim in each correction that the edits "did not affect any of the conclusions" and that "Yield was found to be correct." Years affected: 2006-2013.

Two questions immediately spring to mind:

1. Why have all the corrections exposed thus far been from one country?
2. How far back will we go? Org Lett.'s been around for 15 years...will we soon get corrections like it's 1999?

*Interestingly, Prof. Nakada's group page seems to be suddenly unavailable. Huh.

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)?

Elsewhere...

Retraction Watch guru Ivan Oransky was kind enough to feature my post on Open-Access Corrections.

Science writer Carrie Arnold included my interview as part of a recent story at Science Careers. She's referring to some incidents I laid out in this post from last year.

Winter sun shines through icy trees, Dec 2013

I hear through the grapevine that I'll be part of podcasts at Collapsed Wavefuntion and Chemjobber in the next few weeks. Stay Tuned!

Photochromic Blast from the Past

While digging through some old ACS party favors, I came across this wallet card, which I obtained at an ACS "Kids in Chemistry" event ca. 2001.  A check-in with Mr. Google brings back this 2004 Celebrating Chemistry outreach pamphlet, where the PULS (Photochromic Ultraviolet Light Sensor) card helps budding chemists understand the virtue of UV-blocking sunscreens.

What's missing for us big kids? An explanation of the inner workings of the cards' photochromic dye!

Does anyone with long-toothed ACS volunteer experience happen to know the answer? When did these cards hit the scene? Who manufactured them? What dyes were used? Are they still in use for outreach today?

Fukuyama Mea Culpa in Organic Letters Corrections

Remember all the recent dust-ups over potentially doctored NMR spectra? How about when Organic Letters EIC Amos Smith went on the offensive, hiring a full-time data analyst to sniff out fishy details?

Well, we have a major opening salvo in the war on sketchy Supporting Information (thanks to an anonymous JLC commenter for the tip-off). Seems that Prof. Tohru Fukuyama (U. Tokyo) has issued six simultaneous Org. Lett. corrections in yesterday's ASAP section. (1, 2, 3, 4, 5, 6).

This is a big deal, not least because Prof. Fukuyama's reputation looms large in the synthetic community, but more because the corrections impact challenging targets from his group (manzamine A, huperzine A, lysergic acid, histrionicotoxin) and span multiple years (2008-2013).

Shockingly, the corrections all admit deletion of solvent peaks or impurities from final, published spectra. This correction announces 20 such "edits." In some instances, when the group re-examines the spectra, they're so unreliable that they cannot correct the record: "Samples included some unknown impurities, thus the exact purity could not be determined."

I'm not sure whether to applaud or condemn the Fukuyama group - if they chose to come forward voluntarily to correct the record, I applaud the effort. However, if they were instead strong-armed by the OL Data Analyst, then a culture of data manipulation has been uncovered at the highest levels of our field (reminder: this is just one journal, hold on for the slate of corrections in other venues).

Wish I could say that this meant "Case Closed," but I think we're only seeing the tip of the corrections iceberg in Organic Letters.