Friday Fun: Sweet Cardamom (Peroxide)

Rice pudding. Ginger snaps. And...malaria?

That's what'll be going through my head next time I cook with cardamom, thanks to Tom Maimone and coworkers (UC-Berkeley) and their under-the-wire JACS ASAP from yesterday afternoon. The title and abstract scratch all the Baran lab alumni itches: 1) biosynthetically inspired, 2) novel mechanisms, 3) scalable, 4) just four steps! And hey, we're making stable endoperoxides, which all the cool kids are into nowadays.



Not their actual abstract graphic...

As Maimone points out, the latent symmetry of the final product offers a really neat assembly strategy. The group McMurrys together two units of (-)-myrtenal, then hits it with singlet oxygen, initially forming a 6-membered endoperoxide they fragment / rearrange with base. A gentle oxidation (DMP) sets them up for the wild step: stitching together a 7-membered endoperoxide using Mn(III)*, a radical source, a silane reducing agent, and even more oxygen. Simple phosphine reduction knocks down the last hydroperoxide into an alcohol, and the whole target (7 stereocenters!) falls out as a single stereoisomer.

Pretty sweet.

P.S. - Since the group's made over half a gram in just this first push, I'd assume an efficacy paper against live Plasmodium parasite hot on the heels of this one...

*We're apparently already calling this the "Shenvi catalyst"...wasn't this only two months ago?

Huh?

While catching up on my old issues of C&EN, I happened across this ad on p. 24 of the March 10 issue:

At the risk of sounding insensitive, can someone please tell me what "the Elements Science" means?!? 

Perhaps some editorial help next time? Tamao's world-famous named reaction and many contributions to synthetic chemistry deserve better. I especially love his anti-chemophobia stance on this profile page at Kyoto U:

"It saddens Prof. Tamao that in recent years people have begun to associate negative images such as environmental pollution with the word ..."chemicals" ...He wishes the benefits of chemistry were more widely known. He points out that organic silicon compounds, his field of specialization, are chemicals that play a very familiar role in our lives. We are in contact with them every day without realizing it, in forms ranging from cosmetics to electronics. "When a new organic compound is created the most amazing things become possible, one after another," says Prof. Tamao. As he laughs impishly, it seems as if a flame of creative energy more powerful than the magic spell of the most brilliant wizard is quietly burning behind his eyeglasses."

Topsy-Turvy Corporate Culture - From Tiny to Enormous

Let's face it: We humans are rubbish at logs.

I don't mean the huge cuts removed from tree stumps, but rather the mathematical powers of ten that scale up or down our everyday existence. N.dG.T. related a convincing illustration of our teensy experience relative to outer space in his first stint hosting Cosmos; here's another from the JLC archives.

Now, I've been working in pharma for some time, usually in tiny start-up companies with 10-100 people (log₁₀ = 1-2). Recently, I made the jump to "Megapharma," clocking in somewhere around 5 logs (To calibrate you, the total student population of UT-Austin is ~4.7 logs, and the population of Los Angeles is 6.6 logs). It's professionally equivalent to feeling like a single grain of salt in a heaping tablespoon.

And hey, this is only a two-log difference!

Not that I'm an introvert, either: I've been ENTJ for as long as I can remember. I'm perfectly fine with bustling parties (1.5 logs) or attending conferences with ~3. But this type of scale jump takes some adjustment. I find myself buried in organizational charts, figuring out exactly whose workflow covers my next project. I apologize when re-meeting people I've met two weeks before - just not enough space on the mental whiteboard for all the new names. Gone are the days when I could just poke my head in my colleague's lab to get a reagent, or speak directly to my company's founder. The enormities of scale preclude certain "normal" social interactions.

All this to say that my posting schedule will remain sparse until I wrap my brain fully around this new reality. It's not all bad news: Small sub-groups meet to offer community to new folks like me. Megapharma uses lots of ingenious workplace engineering to make the place seem smaller - potted plants, kitchenettes, warm colors, etc. After a little while, my brain will loosen and change, and you'll see floods of new posts about the joys of meetings (to plan other meetings) and #BigPharma life.

Oh...and more chemistry whimsy. Promise.

WWWTP? Dallas ACS Edition

Update: 3/17 - More photos from the #ACSDallas informant clearly show the mangled chemistry on both the Exposition banner and some promotional backings from the Chemglass booth. Though I understand what my commenters have remarked upon as "artistic license," I cannot believe that ACS supports glaringly wrong structures adorning their conference walls. 

Standards matter.

Exposition Hall Arch

Chemglass booth

From a contact inside the 2014 ACS Spring Meeting comes this picture, purportedly from the archway leading into the Exposition Hall.

Now, before I start jumping into lectures about Texas* Carbons, non-planar aromatics, and the like, could someone out there corroborate?

Once a few comments confirm or deny, I'll commence gently scolding.

*Get it? 

'March Madness' - Cobalt Catalysis?

Catalysis fads come in waves. This shouldn't surprise - when one group finds almost-too-good-to-be-true reactivity, everyone jumps on to ensure rapid publication and novelty for that dusty grant submission.

For precious metals, King Palladium still reigns supreme, though some serious recent coups came courtesy of gold, iron, rhodium, and iridium. But a new challenger now looms on the horizon:
cheap, plentiful COBALT.

Within about a week of one another, the Dong, Chirik, and Yoshikai groups have disclosed some really neat-o transformations that run on the Co(I)-Co(III)* redox engine. Dong's group discovered a new diene hydroacylation. Chirik's installed B(pin) onto heteroaromatics with low loading and no solvent. Yoshikai offers a mini-career-retrospective on his group's efforts to develop several (new to me!) Co reactions, among them hydroarylation, zinc insertion, and acylation.

So, why the sudden upswing in cobalt? For one, relatively new ligand architectures (pincers, NHCs) have allowed access to stable architectures earlier chemists could only dream of. Also, the concept of "reductive" coupling, still in its infancy compared to the oxidation behavior most folks affiliate with top-row metals, has lured younger groups fighting to carve out a career niche.

Let's see how swollen the cobalt catalysis field becomes in the next five years. The next "gold rush?"
Only time will tell.

*As @Organometallica (rightly) points out, these reactions may yet be more complex - say, for instance, a fast Co(I)-Co(II) to Co(II)-Co(III). This could have mechanistic ramifications later down the road (radicals, anyone?), or be responsible for various off-cycle activity / resting states.

The Lion in Winter

Source: ACIEE | Karen Ostertag

Carl Djerassi + Jeffrey Seeman + Angewandte Chemie
= Must-read material.

Just when you thought you couldn't get enough of Carl's 90th birthday festivities, a new collection of personal quotes has appeared online this week. Djerassi - chemist / author / poet / provocateur - does not disappoint. For the more chemically-inclined, it's full of "Didja know?" moments - for instance, Woodward, Djerassi, and Tishler all submitted syntheses of cortisone to JACS within 3 weeks of each other!

The bulk of the text explores Djerassi's feisty, garrulous backlog of quotables. Here's just a sampling:

On his stamp: "Since 2005, people in Austria - by now thousands - have been licking the back of my head"

On publication: "You owe it to the students and those who collaborate with you...you persuaded them to do it, and obviously at the time that it was worth doing. Presumably, if they completed it, it was good enough to be published."

On community: "Scientists operate within a tribal culture whose rules, mores and quirks generally not communicated through specific lectures and books, but rather are acquired through a form of intellectual osmosis in a mentor-disciple relationship"

The rest run the gamut from social movements (performance-enhancing drugs, the Pill, sex, schadenfreude) to deeply personal hurts (professional exclusion, his daughter's suicide), and end on a peaceful, affirming story concerning the motto of the Djerassi ranch (SMIP, but I won't spoil the secret...)

Give it a read, it's worth every minute.