Neotripterifordin by Corey/Liu

Posted January 5, 2007 by totallymechanistic
Categories: Papers

Paul at ChemBark was writing that “the Aldrich catalog ranks #1 on my list of the top desk references of all time”. I agree, it’s a great help when looking for melting/boiling points, densities, etc. However, I have a computer 2 meters from my hood and 1 meter from my desk, so the Sigma-Aldrich website is what I mostly use.

I also have another nice desk reference. It’s the total synthesis paper of Neotripterifordin by Corey and Liu (JACS, 1997, 119, 9929-9930). Actually my desk reference is the supporting information of that paper, which is very well written and contains many common reactions.

The reactions on that paper are, for example:

LiAlH4 reduction
R-OH -> R-I
Wittig salt preparation/Wittig reaction
silyl protection/deprotection
mCPBA oxidation
THP protection/deprotection
MnO2 oxidation
Katsuki-Sharpless epoxidation
Dess-Martin oxidation
Wolff-Kishner reduction
OsO4 oxidation
Pd/C catalyzed hydrogenation
Birch reduction
[2+2] cycloaddition
ozone oxidation
DIBAL-H reduction
Barton-McCombie reaction

Oh, and this is how Neotripterifordin looks like:


There is a nice cascade reaction in that synthesis:

Neotripterifordin cascade reaction

Interesting paper to read. I recommend.

Still alive

Posted December 20, 2006 by totallymechanistic
Categories: News

My apologies for the lack of posting. Flu (or something) kept me mostly horizontal for a few days. Then, thanks to losing those precious days, I was busy doing some reactions I wanted to get done before Christmas. It just feels nicer to go on a holiday when the intermediates are done. And it’s especially nicer to come back from a holiday when the intermediates are done and ready to be wasted in the next failing reaction. Well, hope not. Purifying that 30 g by column chromatography was quite tedious.

And apologies also if someone’s comment has not appeared in the comments. I noticed that this thing has some kind of a spam filter installed by default. I managed to unspam one of them (sorry Uncle Al, didn’t mean to silence you) but I’m not quite sure if some comments were lost.

That’s it for this post. Just wanted to let you know that this blog hasn’t died in it’s infancy. It was just snoozing quietly. More chemistry-related posts coming soon.

Oddity #1

Posted December 13, 2006 by totallymechanistic
Categories: Oddities

I’ve got a new category again. It’s called “Oddities”. I will put there chemical stuff that I find odd/weird/surprising/etc. They probably aren’t odd, weird or surprising to many of you but they are something that made me go “eh… wtf?”. This is the first oddities post.

The sulfone shown below is an intermediate I had during my project (sorry for the mystical “Ar” but I’m just being extra cautious with any unpublished results). The preparation of this intermediate was supposed to be fairly standard work with no surprises, and so there I was sitting in the NMR room running a standard H NMR to verify that it’s the right intermediate. And as soon as I see the spectrum I go “eh…wtf?”. Now pause for a moment and think how you would expect the H NMR (in d-chloroform) of that stuff to look like (you can ignore the Ar protons).

The Ar-SO2CH2CH2Cl

If you are thinking of something like two triplets (2H and 2H), then you are thinking exactly what I was thinking. However, there’s only one sharp singlet of 4 protons at around 4 ppm. I was, of course, quite surprised to see the singlet, so I ran a fast C NMR. Nothing weird there, one peak at 57 ppm and another at 35 ppm. After running some other experiments (e.g. HSQC) I was pretty convinced that the intermediate was ok. Eventually, I changed the solvent to d6-DMSO, and there they were, the triplets. I’m far from being an NMR expert so maybe one of you might want to explain the odd behavior in d-chloroform.

Kharash-Sosnovsky allylic oxidation

Posted December 12, 2006 by totallymechanistic
Categories: Name reactions

Today is the opening day of our new category, “Name reactions”. Here I’m going to write about well… name reactions. I don’t have any particular system how to choose the reactions but I’ll concentrate on reactions that are not so well-known. I think most of my readers (n=1? I know Milo was here) know so much about organic chemistry that featuring, for example, Diels-Alder reaction would be just pointless.

Today’s name reaction is known as Kharash-Sosnovsky allylic oxidation. It was originally described by Kharash and Sosnovsky in JACS in 1958 (DOI link). A more comprehensive study titled “The Copper-Catalyzed Reaction of Peresters with Hydrocarbons” was published 5 years later by Walling and Zavitsas in the same journal (DOI link). Below is one of the examples given by the gentlemen K and S themselves:

Kharash-Sosnovsky allylic oxidation

It might not be a “wow, that’s amazing!” kind of reaction, more like “hmm… interesting”, but quite nice considering that the selectivities are really good. For example, 1-hexene gives only hex-1-en-3-yl benzoate, and none of the isomeric hex-2-en-1-yl benzoate.

Selectivity of Kharash-Sosnovsky allylic oxidation

“How does that work?!”, I hear the audience scream. Well, below is how the authors of the latter article say it works. They have another option also for the last two steps, where the radical R directly reacts with the benzoate anion.

Kharash-Sosnovsky allylic oxidation mechanism

That’s it for today. Feel free to comment.

edit: I replaced the links to .pdfs with DOIs. Thanks to Mitch from Chemical Forums for suggesting that.

Sodium borohydride/iodine reduction

Posted December 11, 2006 by totallymechanistic
Categories: Procedures

Lately I’ve been doing quite a few asymmetric Michael additions using a chiral oxazolidinone, or one of the thio variants, as a chiral auxiliary. Some of the auxiliaries are commercially available but far too expensive for my taste. They can be easily synthesized from amino alcohols which are also commercially available but they too cost more then I’m willing to pay. So, the only option is to make them myself, which is not that bad a choice considering that the corresponding amino acids are not that expensive, especially the L ones. The D ones can be quite pricey. This is how the auxiliaries look like:

Chiral auxiliaries

There are many ways to reduce amino acids to amino alcohols but my favourite by far is sodium borohydride/iodine combination (.pdf), which is not only non-expensive alternative but also convenient compared to, for example, lithium aluminum hydride (see, I don’t like burning labs). Below is how it looks like chemically written:

sodium borohydride / iodine reduction

So, what is actually happening there? This is how I understand it:

Reaction of sodium borohydride with iodine

First, iodine is reacting with one sodium borohydride, so you get borane, sodium iodide, and hydrogen iodide. Then hydrogen iodide is reacting with another sodium borohydride, so you get another borane and another sodium iodide, plus some hydrogen. All that borane is actually the stuff that reduces the acid to alcohol. Very nice and convenient. I’ve been doing it in 200 mmol scale and works just great, giving the amino alcohol in good >70% yield after recrystallization from toluene.

That’s it for today. Feel free to stop by again and comment if you like.

And so it all began…

Posted December 10, 2006 by totallymechanistic
Categories: News

I know what you are thinking: “Seriously, is there really need for a new chemistry blog?”. Actually, I don’t know if you are thinking that but at least I was just a few hours ago. I’ve been an avid reader of chemistry blogs for months and now I just felt that I want to have my own. So what will this blog be about? To tell you the truth, I don’t know exactly. Generally spoken, it will be about synthetic organic chemistry. But what specifically? That I don’t know.

And what’s with the name? I’m a big fan of total synthesis and if there wasn’t the great site called TotallySynthetic, I would probably write a lot about total synthesis. So I’m a big fan of that site, as you probably could have guessed from the name of this blog 😀 That’s where the Totally part comes from.

I’m also really interested in reaction mechanisms. I like knowing how things happen, not just what happens. So I was thinking that I want to write about reaction mechanisms. And that’s how I came up with the name TotallyMechanistic (actually I think someone was suggesting that or something similar some time ago in TotallySynthetic). Had I more imagination, I might have come up with something more original but this will have to do, at least for now.

I don’t know exactly how often I will be posting but once a day is what I’m aiming at.

See, I don’t know much yet. But thank you for stopping by and welcome back. I hope I’ll have my first real post up by then.