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]

Cellphone Charger Electrochemistry

I'm frankly amazed at chemists' rugged pragmatism. Our ilk often repurpose seemingly innocent household items - floodlights, LED strips, paraffin wax - adapting them for making new molecules in interesting ways. Have a peek at this new paper, which appeared* last week in Angewandte Chemie. 

The Aubé group, recently of UNC, wondered whether expensive setups from scientific vendors were potential roadblocks to wide adoption of electrochemistry. Their ideal recipe called for a direct current (DC) source capable of removing two electrons and an H from a lactam to generate an N-acyliminium ion. Looking around, the researchers realized that today's ubiquitous cellphone chargers might just do the trick. Shave back some wires, attach some copper clamps, and presto! Cheap, effective electrochemistry.**

Using their DIY e-chem setup, the Aubé group traps a wide variety of stereochemically-rich acyliminiums as the corresponding methanol adducts (19-93% yields). Now the real fun starts: there's a whole bunch of interesting arylations and other additions to these species one can access using off-the-shelf Lewis acids like titanium tetrachloride or boron trifluoride:

Adapted from Aube, Angewandte Chemie, 2015 ASAP

I'll be excited to see small libraries of diversified products emerge from this work. However, a "one-pot" functionalization - electrochemistry with the desired nucleophile already present - still seems a distant dream.

Hopefully, the apparent ease of operation of "cellphone charger e-chem" prompts other groups to give it a try. If your group dips their toes into this field, please drop me a line in the comments section.

--
*Thanks to Professor Brandon Findlay (@Chemtips) for pointing out this paper!

**I'm tickled pink at how many organic synthesis papers these days include photographic records of reaction setups. I'd like to believe that Blog Syn played a small role in advancing this change.

More Pictures in Supporting Information? Please!

Just stop what you're doing right now, and look at the gorgeous reaction setups in this Nature SI.

From SI page S16. Source: Nature / Baran lab

My kudos to Phil & co - they sure do capture a good visual chronology of their reactions!

Also prompted one of my more tongue-in-cheek Twitter exchanges in recent memory...

@P212121 - Would you say then (wait for it...) that it was JUST LIKE COOKING? @Dereklowe @Chemjobber

— See Arr Oh (@SeeArrOh) December 18, 2014

Do these pics remind you of anything? : )

Tiny Victories from Bloggy Activism

The chemblogosphere has certainly taken an activist turn in the past few years. Remember feeling the excitement of Paul's 2009 NaH oxidant live-blog? The ensuing four years saw chem blogs "cantrilling" space dinosaurs, uncovering IBX's secrets, investigating suspicious TEM images, and even weighing in on Nobel Prize selection. Heavy stuff!

Long-time readers understand that I've been in something of a self-imposed exile in the past few months, owing to a lengthy job search. But I couldn't resist writing about a mini-Christmas-miracle that arrived on 12/26. Seems that Dr. Brian Myers, the current ACS Division of Organic Chemistry webmaster, had acted upon my June post investigating the strange DOC logo:

"As a result of this posting, the ACS Organic Division has reverted to using the older version of the logo where the "D" is more prominent. It turns out the logo was "updated" in about 2007 while trying to make a high-resolution graphic for posters, NOS bags, and such. At that time, the leadership was unaware of the fact that the molecule was supposed to spell out DOC.  

As one senior DOC executive committee member recently wrote: 'I assumed it was a truncated steroid, which made historical sense. However it isn't because the ethyl and methyl aren't attached to the right places of what would be the CD rings.'"

Presto, Change-o!

Huzzah! The corrected logo now proudly adorns the DOC main page, and I even got a shout-out in their FAQs. I'm not gonna lie - I felt a small twinge of pride seeing this tiny change I helped effect.

But how did we get the logo in the first place?

Challenge: Dr Myers wants to know if anyone out there can remember the initial DOC logo designer:

"As far as I can tell, the first appearance of the logo was in 1985 on the NOS Program book; however, I would love to know the history of this including the name of the person who designed the original logo"

Anyone with insider info should leave a comment or email me at seearroh_AT_gmail. Let's put this chemistry "cold case" to bed!


A belated Merry Christmas to all, and hopes for a very Happy New Year
See Arr Oh

Thin Layer Consternation

Earlier today, I was involved in a minor dust-up with some commenters over at Derek's blog. A central issue concerned my (admittedly quick'n'dirty) TLC, which meant to indicate the complete consumption of the acrylate starting material for Blog Syn #002.

Well, since I was already running another entry for #003, I decided to pause and take stock of my TLC tool-box: yes, I should use a ruler, and yes, a classic TLC would have lots more info (solvent system, stain, clearer labels, etc).

So, I took a sample from my IBX oxidation of methylnaphthalene to 2-naphthaldehyde (12 h timepoint, set up in straight DMSO with 0.1 volume of H2O). Results below:

Before anyone goes crazy, that's DMSO / H2O on the baseline, and the SM at Rf ~0.8. It's stained in potassium permanganate, which forms pale yellow spots upon heating. I circled the "UV-only" spots with a pencil before staining.

I'm guessing that the tiny new spot (Rf ~0.45) represents trace aldehyde. But, as you can tell, we're still a long, long way away from completion. Sad, because it was a lot more homogeneous this time!

Readers: How's my technique? Have any more pointers?

Elsewhere...

Chemophobia got you down? Need a laugh? Call the Chemistry Avengers!

Hey, check it out: Blog Syn #002 is live!
(And I hear that #003 is well on its way...)

More to come at JLC in the next few days. Stay tuned!

Traffic Cones

Well hello there, new reader avalanche! (And thanks, Nature News!)
Update: Thanks, Chemistry World!

I'm See Arr Oh, and I humbly welcome you to my tiny corner of the Internet. If you've come here looking for Blog Syn, you should probably check out my collaborators B.R.S.M., Matt, and Organometallica.

If you've got a few minutes, have a look through some JLC "classics."

• Space Dinos!
• Arsenic Life
• Chemistry Popularity Conundrum
• Fluorophlogopite!
• Hulk Hogan (Ouabagenin)

I look forward to seeing you back here someday. Thanks for coming!

Blog Syn - It's ALIVE!

Remember how exciting it was back in 2009, when Paul over at Totally Synthetic posted his "NaH as an Oxidant - Liveblog," and the whole chemical community rushed to try the same reaction?

Well, we've tried to borrow a bit of that same spirit for the launch of Blog Syn, a new collaborative effort between a few chemblogosphere regulars. Go have a peek at the first post, on Fe-S cyclization reactions, and help us improve with some helpful comments.

Thanks again to my steadfast collaborators and "brothers" in chemical crowdsourcing: Matt Katcher, B.R.S.M., and Organometallica. We're on the lookout for more reactions to try, so don't hesitate to get in touch - seearroh_AT_gmail.

-SAO

Escalation: Authors Respond

Regular readers know I sent out an inquiry to the Fe-S authors a few days back:

Dear Prof. Nguyen:

Good afternoon. My name is See Arr Oh (a pseudonym), and I write a chemistry blog called Just Like Cooking. I've posted about one of your recent publications in JACS ASAP:

http://justlikecooking.blogspot.com/2012/12/desert-island-chemistry-simple-as-fe-s.html

http://justlikecooking.blogspot.com/2012/12/call-to-arms.html

Another chemist at Princeton graciously offered to repeat one of your reactions (Table 2, entry 2), and could not duplicate your group's yield or purity. Further discussion can be found in the comments section of the second post. Additionally several other members of the chemistry community have expressed an interest in running it themselves, with the intention of aggregating data under the Twitter hashtag #RealTimeChem.

Please share some more information - do you have any hints or tips for successful duplication? 

Thank you in advance,

See Arr Oh

seearroh@gmail.com

Unfortunately, my spam filter ate the (prompt) response, and thus I'm posting it a few days later than when I received it back on 1/2/13:

Dear See Arr Oh,

Thank you for your mail. First, you should carry out the reaction in the same scale as described, otherwise, sulfur is comsumed by reacting with methylhetarene before combining with iron. Second, a vigorous stirring is necessary to disperse iron powder into the reaction mixture. At this temperature, the reaction mixture is homogeneous except iron powder. Third, the reaction should be carried out under Ar atmosphere because oxygen is not an innocent impurity. Oxygen in the reaction tube is best removed in vacuo (10 mmHg is ok) then the tube is filled with Ar. This cycle is repeated twice. Before running an NMR spectrum of the crude mixture, paramagnetic iron residue should be removed by syringe filtration to avoid any magnetic pertubation. In most cases, the products were formed as black solid. The prduct is fluorescent with UV lamp.

Sincerely

Nguyen

Interesting tidbits: vigorous stirring, as opposed to a debate in the comments over whether we should stir the reaction at all, scalability issues, and recommendations for NMR analysis - Fe junk really does mess that up!

Methinks this advice might come too late* for anyone trying the reaction today; sorry, B.R.S.M.!

*Addendum - That's a lot of "insider info" in that email, and I'd argue a lot of the online discussion we've had on this reaction could have been avoided by a more complete Supporting Information file. None of that info was available either there or in the paper, nearest I can tell. Readers?

Turning Wishes into Horses

A fantastic summary crossed my desk today, courtesy of the RSC's Chemistry World. It profiled a new reaction from the Milstein group, just reported in Nat. Chem., that just looked so tempting: oxidation of a primary alcohol, using water as the "O" source, with hydrogen gas as the lone byproduct.*

And thus began what my brain usually does, "Science Wish Syndrome." Not familiar? Here's the stages:

1. Unbridled Enthusiasm - "Holy cow, that reaction looks fantastic! I'm sure it will produce 20 new analogues / help me wrap up my thesis early / solve world hunger. I can't wait to try it!"

2. Skepticism / Doubt - "Well, Blogger X tried it, and couldn't reproduce the yields. And the Supporting Info says it only works with 100 mesh hyper-refined silver powder sourced from Argentina. Still, it's in Nature / Science / JACS / Angew Chem, so it must work, right?"

3. Despair - "I ordered all the reagents, and used my last 0.3 mg of shootmenowicene in the test reaction. I barely got 10%, and it's a mixture of stereoisomers! Who the heck let this into this journal?"

Readers, does this ever happen to you? Modern chemistry publication, with ASAP format, DOI codes, PDB uploads, and overall rush to publish before the guy on the other side of the pond, seems forced somehow, and doesn't always live up to the glowing reviews crowed about in press releases.

Over at Not the Lab, Vinylogous has suggested that we compile a sort of post-hoc online review journal, playfully named "Blog Syn" (after 800-lb-gorilla-in-the-room-for-synthetic-methods Org. Syn.).

Well, how might something like this work? I'd assume that the community would have some sort of mechanism to suggest papers, say, for when too-good-to-be-true chemistry like the NaH 'oxidation' comes 'round. A central aggregation point, perhaps cultivated by an "Editor / Blogger" would then issue requests for duplication. To ensure results were processed in a timely fashion, a deadline would be suggested (2 weeks?) and the "Duplicators" would have to authenticate that they tried to cleave to the original conditions as best they could. A digital "Stamp of Approval" might then follow the reaction through the online world, indicating, much like Org. Syn., that the reaction works in others' hands.

Readers, would anyone like to be part of such an effort? Methinks the #RealTimeChem crowd could get excited about this. Yes, I know everyone's busy, and this isn't the first thing you think of when there are proposals to write, classes to teach, or conferences to attend. But the literature will only be as good (or as bad) as the folks who contribute, and we desperately need more quality control.

*Update - It occurred to me (too late!) that I sound like I'm condemning the Milstein reaction, which I have not tried, and have no reason to suspect won't work as of this writing. I just wanted to use it as a backdrop for seemingly "perfect" reactions that end up not living up to expectations. The reaction, as reported, needs some scope exploration, so only time will tell if it's as widely applicable as I'd hoped.