Post Tagged with: "ACIE"

Hoveyda’s Asymmetric Mo-Catalyzed Metathesis

I recently had the pleasure of listening to an excellent talk by Amir Hoveyda about his chiral-at-metal Mo catalysts for asymmetric metathesis. This kind of catalyst is based on the Schrock-type molybdenum catalysts. Most asymmetric catalysts nowadays employ bidentate ligands such as BINOL-type ligands that carry the stereochemical information. By chelating the metal centre, the fluxionality1 is reduced, therefore ensuring a well-defined geometrical arrangement of the catalyst-substrate complex and good stereoselectivity. In addition, the loss of stereochemical integrity of the catalyst is suppressed. Hoveyda has used such complexes to achieve the formation of P-stereogenic phosphinates and phosphinoxides (where the phosphorus is a chiral centre) by desymmetrizing RCM of achiral precursors (ACIE: 10.1002/anie.200805066).

Desymmetrizing RCM generating a P-stereogenic phosphinate/phosohinoxide

There is, however, a downside to reduced fluxionality. As Hoveyda points out, the Mo complex has to undergo a series of geometrical rearrangements during a catalytic cycle. If the complex is too rigid, these rearrangements are hindered. In other words, you may get high e.e.’s, but the catalytic activity will be low. This is where chiral-at-metal catalysts have a clear advantage: they only require monodentate ligands, which makes the complex more able to rearrange, and the reaction will be much faster.

The excellent stereocontrol is due to electronic effects rather than pure sterics. One of the ligands has to be an acceptor (the BINOL-type ligand) that ensures sufficient Lewis acidity of the metal centre. A donor ligand (the pyrrole) is also required because it distorts the complex geometrically in a way that facilitates the coordination of the alkene substrate. The use of this kind of asymmetric RCM is demonstrated in a total synthesis of (+)-quebrachamine, where they get a yield of 84% and an excellent 96% e.e. (Nature: 10.1038/nature07594).

Asymmetric RCM in the quebrachamine synthesis

I have only touched some of the most important points made in these papers. They are definitely worth reading!

1 I wasn’t familiar with the term “fluxionality”. Apparently, it is often used in organometallic chemistry to indicate the possibility of interchanging between equivalent conformational arrangements. As a simple example, Wikipedia mentions the interchange of the two Me groups in dimethylformamide. A monodentate ligand in a metal complex is fluxional in the sense that it can rotate around the metal-ligand bond.

By December 26, 2008 0 comments synthetic chemistry

Full Frontal JACS

The Journal of the American Chemical Society (JACS) has flirted with web 2.0 with it’s recent JACS β initiative. It has been warmly received around the blogosphere [CSB, TCB, CBC]. Although, I don’t have any complaints about the website, what I really wanted was less hand-holding and more of a shotgun approach to navigating through JACS online.

The nicest thing about thumbing through the print edition of JACS, is reading all the various chemistry that is outside your research tunnel-vision but still interesting.  If you go to the JACS homepage, here, you’ll see a list of 20 of the most recent articles, but not all of them! For example, 31 papers were added to ASAP today and only the last 20 are shown on their website, hardly a dire circumstance, but the fact is you miss some by using that setup. JACS also offers a nifty RSS feed of their articles, but I’ve never come across an RSS reader that’ll nicely format an active feed, 30+ submissions a day, in a format that will ever make me want to read it.

So how does one go about designing a more attractive JACS online browsing environment? Below is my attempt, it is as busy and attractive as a conference poster, but it lets you see a huge list of the most recently added papers to JACS ASAP.


The website parses through the JACS RSS feed. I was a bit worried about incorporating the graphical abstracts, but since they are included in the RSS feed, I’m going to claim fair use. The site isn’t pretty, but it gets the job done.

Here is a link for your viewing pleasure, Full Frontal JACS:

Comments are always welcomed, but obviously this format is not for everyone.

Edit: A link to the site has been included in the links section to the right, towards the bottom under websites, titled Full Frontal JACS.

Update 1: Improved ACIE RSS feed

Update 2: Links edited to point to ChemFeeds instead of the simple script.


By October 9, 2008 8 comments chem 2.0

Diaza[12]annulene: Would You have Known Better?

The recent retraction of two papers regarding diaza[12]annulenes by Yamaguchi et al. and Shi et al. from separate groups have strengthened the argument for stronger peer review and more thorough literature review by authors.

But anyone can be an armchair synthetic chemist and point fingers at what should have been done after the fact. The easiest finger to point, is presumably between 7 coauthors, 4 reviewers, 2 editors no one ran the appropriate literature searches to find that these reactions are known and yield products with exactly 1/2 the mass as those reported in the papers. But, now we come to the bitter truth in modern chemical research, we simply do not perform the thorough literature searches of yester’year. Some will say this is a problem, but assuming those 13 scientists are typical of scientists of today then it simply isn’t a fair commentary to make. So, I thought it would be more beneficial to reread the papers and see if I would have come to the same conclusions given the same series of data, as I’m oblivious to heterocyclic chemistry in general and the Zincke reaction in particular, and have a typically topical background like most chemistry graduate students (I’m a Nuclear Chemist after all).

First up the Yamaguchi paper:
The title is the One-Pot Synthesis of N-Substituted Diaza[12]annulenes. Just looking at the title, we should be expecting 1H,13C-NMR, definitely MS data, and likely a crystal structure since the molecule would have two cationic-like centers. Picture shown below.

As can be seen in the structure this monstrosity should have some serious pi-pi stacking possibilities, and isolating crystals shouldn’t have been too problematic, but none are isolated. An image of their NMR data for the structure above is below.

It would be at this point that the little voice in my head would be like, “hmm…. why do I have aromatic proton peaks? I should probably count those pesky buggers again. Yup, 12 delocalized electrons.” If one is postulating that this is antiaromatic, then one hallmark of antiaromatic hydrogens, located on the outside ring, are that they shift upfield (lower ppm) and lie to the right of 8 ppm and likely 7ppm. So, it would have been at that point where the paper would of confused me.

Second up the Shi paper:
The title is the [12]Annulene Gemini Surfactants: Structure and Self-Assembly. So, we should be expecting yucky yellow oils, and with the word structure, perhaps even a crystal structure. The molecules examined are shown below.

Independently, they confirm the odd aromatic protons of Yamaguchi and they obtained a yellow powder, not necessarily an oil, but well within reasonable expectations. They did some calculations with Gaussian and discovered the results below.

The expected distorted structure is seen in II but lied 1.7 kcal/mol higher in energy than I. This is just odd, for a cyclic antiaromatic system we should expect to see 2nd order Jahn-Teller distortions shift the molecule away from planarity and this was not seen by calculations. This is where the authors and reviewers can be faulted, at that point some one should have suggested an experiment to see whether the NMR peaks would move upfield as a function of temperature. As scientists, we love making graphs, and that would have been a neat confirmation of both the structural predictions from calculations, and an easily verifiable hypothesis.

In summary, I don’t feel it is fair to fault the authors, reviewers, editors for not knowing every obscure heterocyclic named reaction. However, it is prudent upon all of us to ask the right questions about our research, to put-off deadlines if necessary, and to apply our full intellect and diligence to our experiments.

Some Armchair commentary here:


By December 14, 2007 2 comments synthetic chemistry

Plutonium Polymer Mystery Solved

Earlier this week a paper by L. Soderholm et al. in Angewandte Chemie may have solved the great plutonium polymer mystery. Plutonium polymer is the ubiquitous noun often spoken by plutonium chemists in regards to the un-extractable ill-defined hydrous oxides of plutonium that will form in any solution of aqueous plutonium lying about the bench top. Often plutonium polymerization can be inhibited by storing aqueous plutonium solutions at high acid concentrations. It was thought to form from a series of olation reactions:Plutonium Olation Reaction: Pu—OH + Pu—OH2 —> Pu—OH—Pu + H2O

This old hypothesis is put to rest with the isolation of Li14(H2O)n[Pu38O56Cl54(H2O)8]. This occurred after repeated anion-exchange with an acidified alkaline peroxide solution of plutonium, that then crystallized in the presence of aqueous LiCl. This type of workup is common for samples containing plutonium polymer. The crystal is reported to have the same intracluster packing and structural topology as bulk PuO2. The crystal structure of the [Pu38O54(H2O)8]40+ is shown below-left and a picture of the [Pu38O56Cl54(H2O)8]14-is shown below right.

Plutonium cation nanoclusterPlutonium cation nanocluster

Reprinted pending permission from John Wiley & Sons, Inc.: Angewandte Chemie International Edition (Dec 2007).

The Plutonium is in green, oxygen from the oxide in red, and oxygen from water in blue. With this and other evidence of well defined Pu—O clusters and the lack of hard evidence for oxyhydroxides they expect plutonium to condensate through an oxolation reaction.

Plutonium Oxolation Reaction: 2Pu—OH —> Pu—O—Pu + H2O

The one caveat with this work is that it was performed with the more stable plutonuium-242 (t1/2=3.7 x 105 y) and not the typical reactor plutonium-239 (t1/2=2.4 x 104 y). Perhaps in the presence of the >10x more radioactive Pu-239 the nanoclusters would become either too structurally damaged to resolve nice crystalline structures, or more chemically reactive towards hydrous oxide formation or oxyhydroxide formation. Regardless, this work may still lead to better methods of extracting plutonium out of the nuclear fuel cycle and represents a nice resolution to the nebulous plutonium polymer conundrum.

Link to Paper:


By December 13, 2007 0 comments nuclear chemistry