Wednesday, August 26, 2015

Giving Up Benzyne

From Rolf Huisgen's highly detailed and comprehensive biography The Adventure Playground of Mechanisms and Novel Reactions comes this rather eyebrow-lifting passage:
"I had several reasons for abandoning benzyne chemistry at the beginning of the 1960s. Many groups were active in the field, and other areas like 1,3-dipolar cycloaddition began to blossom in Munich. In addition, Georg Wittig, my venerated senior colleague, signaled in print and word that he regarded dehydrobenzene as his domain."

Left, benzyne, in one of its (many) accepted resonance forms
Right: Emeritus professor Rolf Huisgen, of dipolar cycloaddition fame

I wonder: Given the advances in benzyne chemistry over the past 112 years, and that up-and-coming groups make its study a central piece of their research portfolios, would this choice be made in today's research landscape? Readers, have you ever been asked to cease your studies in a certain area because someone more prestigious laid claim?

Tuesday, August 18, 2015

Fall ACS: Epic Tweet-up

Kudos to all who braved the blinding snow searing heat one-mile walk to Lucky's Lounge last night for the biggest ACS tweet-up on record (at least among the few I've attended!).

Folks I remember dropping by include:
N.B. Please toss me your name in the comments if I've inadvertently left you out!

@Dichtel, fresh off his Kavli lecture success
@SuperScienceGrl, our fierce vegetarian
@stephengdavey, Nature editor
@CrimsonAlkemist, polymers guy in sharp shirt
@DrRubidium, Communicator, Forensicist, superstar
@ChemProfCramer, needs no introduction to this crowd
Jeff Seeman, chemical historian extraordinaire
@curiouswavefn, molecular modeler and chief organizer

A candid shot from inside Lucky's
Names are withheld to protect the innocent.
@sciencegeist, professor and blog stalwart
@Free_Radical1, nice dude from DE
@UnstableIsotope, polymer chemist and sometimes spider-kitten
@gagliardi8, Modeler and fellow Italian
@petercarlton, keeps CAS social media in line. Also, Dungeness crabs.
@CMcCinDC, looks like Derek Lowe. Nice tie!
@Waghornscience, ACS videos star
@laurenkwolf, (also) famous for ACS vids and, y'know, editing, too!
@amandayarnell, (see above). Too popular.
@CHADNANO, Nano-ink Prof at NW
@MurphysLab, polymer defects, live from Canada
@barneygrubbs, the nicest, tallest tweep you'll meet
@JuliaKalow, MIT wunderkind
@katmatcher, another MIT wunderkind who helped vet reactions!
@CEN_Onion, secret secret, I got a secret (and no, he's not me)
@JamesBatteas, TAMU 2D polymer champ
@GriceChemistry, super-nice wrangler of undergrad research group

Thanks to all for a great night out!

Saturday, August 15, 2015

Hyperspeed Hyperforin

Kudos to the Maimone group (UC-Berkeley), who have published in JACS ASAP what seems to be the speediest synthesis of a hyperforin on record - just ten steps!

Perhaps this lends more credence to the Eastgate's "current complexity" index, which measures synthetic simplification over time thanks to improved methods. But who would have guessed that in just five short years this synthesis would telescope from 50 steps down to just 10? Strychnine, albeit a very different challenge, took nearly 60 years to simplify from 30 steps down to Vanderwal's highly-convergent six.

For Chemists: Steps of interest include a highly-oxidized [4+2] diketene cycloaddition, a iodoacetate-promoted ring expansion, and a highly modular synthesis widely amenable to analogue production.

For Everyone Else: Why should I care that this ungainly-looking molecule was made faster than before? First, hyperforin and related secondary metabolites (natural products produced by living organisms) isolated from famous folk remedy St. John's wort suggest new avenues for the treatment of of malaria and certain forms of depression. Second, if chemists can make variations on this molecule in roughly one-fifth the time, we can expect a venturesome start-up somewhere to begin fleshing out the SAR (what chemical modifications product what activities?) in record time.

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.

JLC at ACS Boston Next Week!

Still creepy.
Thanks, Carmen.

Excited as always to learn some new chemistry and stalk the Exhibition Hall at the 2015 ACS Fall Meeting.

I'll live-tweet a bit using the #ACSBoston hashtag. If you see anyone dressed like this (right), be sure to run the other way...

Looking forward to seeing some of you there!

UPDATE (15 Aug): From the shameless self-promotion desk, this request - if you're stalking the poster sessions or oral presentations, and you hear someone say "...and I'm so glad to be a new member of the faculty at Big State University!"

Please take a moment to jot that person's name down, and compare it against our ongoing collection. I'm willing to bet, ACS National Meetings being the social hotbeds they are, that a few faculty moves have slipped under the radar...

UPDATE 2: I hear tell that there's a tweet-up planned for Monday night. More details when I have them (and when I learn if I'm somehow interfering with others' plans!)


UPDATE 3: As announced on the Twitterz, one of my goals for this meeting is to befriend the venerable Professor Molenium, and somehow convince him to pose with me. If you spot the mole, be sure to tweet at me!

@seearroh

Friday, July 31, 2015

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
--

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

Wednesday, July 29, 2015

"But...This Synthesis Goes Up to Eleven!"

Have you had fun reading through all the hilarious send-ups on the Twitter hashtag #HonestChemTitles? This tag tries to dig down to the subtext behind highfalutin words and strange symbols, uncovering the hidden motivations behind scientific papers. And...it's a hoot.

Remember the tweet that kicked off this brouhaha? A harmless convergent synthesis of some Lycopodium alkaloids. Kudos to @AlexFGoldberg for highlighting the authors' rather overblown title:


Classic children's literature;
my first exposure to superlatives
Amazingly, that 10-word title is 30% superlatives and 30% chemistry, with a smattering of conjunctions and articles to connect them. As others pointed out, how do you measure "elegantness," anyway? And when does a total synthesis cross the line from concise to exceedingly so; can anything more than a one-stepper be really succinct?

Sort through the paper with a grammarian's fine-toothed comb; one wonders if it wasn't run through some sort of excitement thesaurus, perhaps to get people really stoked about these routes.

Here's all the intense words and expressions I found:

Diverse
Useful
Unique
Challenging
Efficient
Complete
Direct
Achieved
Accomplished
Value
Exceedingly concise and convergent
Attractive

...and that's just in the first paragraph, folks.

Nigel Tufnel (Christopher Guest), ca. 1984
Honest opinion? Aside from the goofy title and superlatives liberally sprinkled into the text, the chemistry seems solid. Nothing's breathtaking - setting an early quaternary center through steric control is nice, and telescoping the three steps before the desired tetracyclic dione works well - but there's no "killer reaction" for me in this paper. The NMRs are clean, and the synthesis represents a decent improvement over existing methods.


Thus, I'd like to accept this publication into the "Spinal Tap Synthesis" category, so-named for the hard rock auteurs profiled in 1984's This is Spinal Tap, the tongue-in-cheek rock mockumentary. If you've never watched the movie, I won't spoil it, but I highly recommend the sequence in the middle where Nigel Tufnel, the vapid, misunderstood lead guitarist, obsesses over a "special" amp he designed that "goes to 11."

Fits this paper to a T.