On NHC-gold complex-catalysed aryl protodecarboxylation

Here the group of Prof. Nolan (University of St Andrews, UK) revisits the classic protodecarboxylation of arenes with a twist, a golden twist. No need for strong basic conditions anymore, a dash of NHC-gold complex, heat, and it’s done!

10 Reference: Chem. Eur. J. 2013, 14034-14038. link

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Base-controlled enantiodivergence in α-aminonitrile acylation.

The groups of Prof. Takeda (Hiroshima University) and Dr. Otani (The University of Tokyo) have come across a rather surprising outcome in the α-acylation of aminonitriles: under otherwise identical conditions, the choice of base (LDA vs. MHMDS) had a dramatic influence on the retention or inversion of the stereocentre.

11Reference: Angew. Chem. Int. Ed. 2013, 12956-12960. link

7. On cyclopropane C-H activation.

If there is a topic of catalysis that has been restlessly growing these past ten years, it is without much doubt the field of C-H activation. In it, C-H activation on Csp3 positions proves difficult, though more and more methods are developed. In particular, the C-H bonds borne by cyclopropane moieties seem to be activated reasonably easily by palladium complexes.

In 2012, the group of Prof. Nicolai Cramer of EPFL (Lausanne, Switzerland) reported a new enantioselective method for the synthesis of cyclopropane-fused tetrahydroquinolines via palladium-catalysed cyclopropane Csp3-H activation.

7.b

The only downside of the method is the mandatory substitution on the R position. In the case where R = H, the favoured product is the corresponding spiro dihydroindole compound.

7.a

This is easily understandable as the 6-membered ring product must come from a 7-membered ring intermediate whereas the 6-membered intermediate would be favoured, affording the 5-membered product.

7.c

Reference:
Angew. Chem. Int. Ed. 2012, 51, 12842-12845. link

6. A new way to make methyl esters.

If you are planning to convert a carboxylic acid into the corresponding methyl ester, chances are your two main plans will be the Fischer esterification or the reaction with a methyl electrophile. While the esterification is one of the easiest reactions to perform, you will need strong acidic conditions, and not many organic functionalities will stand it. Otherwise, if you do not mind to use slightly basic reaction conditions, the use of methyl iodide or dimethyl sulfate (or even worse, diazomethane) generally does the job and does it well. The downside, of course, is the notorious toxicity of these bad boys. If not acute, they will methylate anything they find, and if you are not cautious, it may well be your lungs or your DNA (remember these are very volatile species, and dimethyl sulfate was once considered as a chemical weapon, but as I remember it, it was not deadly enough).

6.aA new way to get around this whole toxicity issue is described in one of the last papers from the team of Dr. David J. Gorin (from Smith College, Northampton, MA). Here dimethyl carbonate plays the role of the methylating agent, and the good news are, it is cheap, readily available, the boiling point is quite high (90 °C) and it is fairly harmless compared with methyl iodide and dimethyl sulfate.

6.bThe yields are good to excellent (75-99%) and the method is chemoselective. In fact, this methylation does not affect unprotected phenols, so there is no point in worrying about having a product mixture or struggling with protecting group manipulation.

Reference:
J. Org. Chem. 2013, 78, 11606-11611. link

4. Electrochemical chlorination of 1,3-dicarbonyls

A recent paper of Prof. Fumitoshi Kakiuchi et al. (from Keio University in Yokohama, Japan) deals with the copper-catalysed α-chlorination of 1,3-dicarbonyl compounds.

You might be thinking that it is just another paper on an overused method, but there is a twist here that I particularly liked. The source of chlorine here is nothing but hydrochloric acid, probably the cheapest and simplest source of chlorine atoms, without the issue of handling a toxic gas like Cl2. I guess there is no point in mentioning N-chlorosuccinimide. The trick for the transformation of a fairly inert Cl into a formal Cl+ is the use of electrochemistry. A mild current at the appropriate intensity provides just enough oxidation to provide monochlorinated 1,3-dicarbonyls in ok-to-high yields.

4.a

While I doubt I will ever use this method in a lab (I am not too experienced with organic electrochemistry), I can see the potential of it on an industrial scale: reducing costs of reagents, reducing waste, and perhaps you could even use the H2 produced by the reaction to power an auxiliary generator or something.

Asian J. Org. Chem. 2013, 2, 935-937 link