B.R.S.M. When all you have is a hammer everything looks like a nail

29Jan/132

Guest Post: 50p

As some of you might remember, towards the end of last year DrFreddy over at Synthetic Remarks offered out his services as a guest blogger to anyone interested, purely for the fun of blogging somewhere new for a change. I took him up on his kind offer, and this post is the result. Anyone else interested in writing a guest post (or having me write one) should get in touch. Enjoy!

When I first came to London I was only sixteen
With a fiver in my pocket and my ole dancing bag
I went down to the dilly to check out the scene
And I soon ended up on the old main drag

That's the first verse of one of the best songs ever written and performed.

When I was seventeen (not sixteen — and it wasn't my first time in London — but still), me and my then girlfriend went on a weekend trip to London. It was awesome in every aspect. Unfortunately, I can't bring back every detail of it today, and for that I blame the synergistic effects of ethanol and teenage love (CAS # 51-61-6) on your central nervous system. One thing, however, will never be forgotten — and I still possess the physical proof (vide infra).

On the Sunday morning, we took a boat out to the Greenwich Observatory. By the way, did you know that is was we Vikings who first named the place?[1] Anyhoo, apart from literally standing at the center of time and taking in every revelation that comes with it, we got hungry. So, we started looking for a place to eat. Mind you, this was in the early '90s, and large tracts of Europe were still not perfectly adjusted to a free market economy, so every street corner was yet to be blessed with a 7-Eleven (True story, kids!).  It turned out that we couldn't find a single open pub or restaurant or any place that would sell us something edible. But, on one street we found open store.[2] Antique books.

I love old books, it's not that. But when you are hungry, slightly hung-over and your teenage love deserves a meal, your main priorities might be elsewhere. However, our return boat was another hour away, so I decided to check the place out anyway. My girlfriend waited outside. In anger.

I made it quick. I came out with this.

Practical Chemistry

For the record:

Title: Practical Chemistry
Authors: Bruce and Harper
ISBN: ?
Publisher: Macmillan and Co Limited
Publication date: 1947

It set me back 50 pence, and I decided to just take it before flipping it open. Its pocket size, the nice patina and the word "chemistry" on the cover; good enough.

Back in Stockholm, Sweden several weeks later was probably the first time that I gave it a real chance. Little did I realize then that this was hands down the best investment I had made in life so far (and maybe to this day). Also, that it would strongly contribute to choosing the path that led to who I am today, for good or bad.

This little one had everything. First, I read it. Then I read it again. Before I knew it, I had memorized every page. I set up a laboratory in my boy room. It grew bigger and crazier by the day, and my risk assessments were in hindsight not stainless.

TNT recipe

I'd like to wrap this story up with a confession: Yes — I did at one time synthesize TNT according to the recipe presented. On the kitchen stove, no idea of what I was really doing, a late night when my parents were away, in a 500 mL Erlenmeyer flask, into a boiling mixture of concentrated nitric and sulfuric acids went a squirt of toluene, and out came eventually a yellow solid that stained your fingers upon touching it, and judging by ocular inspection, in a total yield of a few milligrams (<1 %).[3]

What is the best investment of your life so far?

Written by Fredrik von Kieseritzky who blogs as DrFreddy at Synthetic Remarks

 

[1] Kind of a stretch admittedly, since I likely have very little real Viking DNA in me.

[2] In this context, I should probably say "shop." — And maybe consider putting the closing quotation mark before the damn period. No! Full stop... aarrgh....

[3] I just consulted with a lawyer friend of mine, who uttered the magic phrase "statute of limitations." Still everyone — do not try this at home!!!

Filed under: Guest Post | 5,485 views | 2 comments 2 Comments
20Jan/138

(+)-Hyperforin (Shair, 2012)

Okay, I've finally got round to a full post on this synthesis. I started writing this almost two weeks ago! More things soon. Enjoy!

 

Enantioselective Total Synthesis of Hyperforin

J. Am. Chem. Soc., 2013, 135, 644 | [PDF][SI][GROUP]

B. A. Sparling, D. C. Moebius, and Matthew D. Shair,

DOI: 10.1021/ja312150d

 

3220px-StJohnswort-leaves

It's a little surprising how few people have made hyperforin, considering that it's been known for over four decades. Indeed, the list of groups with partial solutions and 'studies towards' is an august company indeed: Nicolaou, Chen, Nguyen, Mehta, Jacobsen and several others have all fallen at various hurdles along the way. The compound itself was first isolated in the early seventies from Saint John's Wort (Hypericum perforatum), and is believed to be responsible for the well-documented antidepressent activity of the plant and its extracts, which are popular herbal supplements. No-one's quite sure exactly how it works (although as I understand it that's pretty normal for anti-depressants), and its undesirable physical properties make it an unlikely drug, but perhaps if the right analogue could be made then it could be the next big thing for tormented grad students. Surprising, then, that the only reported synthesis of the molecule before Shair graced the scene was published by Shibasaki in 2010 and although that contained some tasty chemistry (the Fe catalysed asymmetric Diels-Alder and vinylogous Pummerer were my personal highlights), at 51 steps it was perhaps a bit long to do much medicinal chemistry with.[1] The Shair group saw a better way, disconnecting the molecule back to 6 key building blocks:

retro

Credit: J. Am. Chem. Soc., 2013, 135, 644

Filed under: Current Literature, Total Synthesis | 11,041 views | 8 comments Continue reading
16Jan/136

Who Ya Gonna Call? Blog Syn!

Ever see a reaction in the literature and think, "that seems a little too good to be true..."? Retro Baeyer-Villiger reaction? Quantitative cleavage of methyl ethers with Amberlyst-15? Catalytic reduction of alcohols to hydrocarbons with Dess-Martin? Bring it on! Ever struggle with a sensitive or fiddly reaction and wonder, "is it just me? Should this work?"? Well, now you don't have to! Thanks to a collaborative new website brought to you by See Arr Oh, with a little help from Organometallica, Mat Katcher and Myself. Now, if you find a reaction you can't reproduce or don't believe, simply head over to Blog Syn, and let us know.[1] Alternatively, if you think you'd like to be part of helping to make the literature a little bit more reproducible, pay us a visit and see what needs checking! If we all just run a few extra reactions a year we should be able to save chemists around the world many wasted hours and much frustration. You might even have some fun, make some new friends, and perhaps even learn some chemistry besides!

1. Or email See Arr Oh or myself

Filed under: Ask the audience, Current Literature, Fun | 4,018 views | 6 comments 6 Comments
3Jan/1312

Barium(ii) Iodide – The Shair Method

Full post on this synthesis to come when I get back from holiday at the weekend and can use ChemDraw! Sorry for the hand-drawn stuctures - I've still not found a good way to draw stuctures on my iPad, which is all I have with me.

I've never been particularly excited by phloroglucinol-derived natural products, but I really enjoyed Shair's recent synthesis of the polyprenylation acylphloroglucinol (+)-hyperforin (it's a PPAP!), which appeared in the JACS ASAPs a few days ago.

  

I'll hopefully get round to a more detailed discussion of the route in the next week, but the first step immediately caught my attention. The chemistry's simple enough - a good old-fashioned deprotonation step with t-BuLi, followed by treatment with  barium(ii) iodide and prenyl chloride. I remembered (after looking it up) that the prenylation is done via the organobarium to improve the regioselectivity of the reaction, a trick developed a couple of decades back by the Yamamoto group (J. Am. Chem. Soc., 1994, 116, 6130).

Still, I was curious about how the group carried out the reaction, and on what scale, so I delved into the SI (which, by the way, is excellent). There I found a slightly unusual tip for how to get the small barium pieces necessary to freshly prepare the BaI2:

"Using a hand drill hammer, a chisel, and a lead brick positioned on the laboratory floor, mineral oil-coated barium rod was portioned into approximately 25 mm segments... If a hand drill hammer and chisel are unavailable, a standard claw hammer and an appropriately-shaped shelving bracket may be employed in this step."

I'm not sure why, but seeing that in a JACS paper made me smile.

 

 

Filed under: Uncategorized | 6,198 views | 12 comments 12 Comments