Art of Synthesis

Robert Grossman mentions in his book "The Art of Writing Reasonable Organic Reaction Mechanisms" that if you cannot classify an alleged pericyclic step in your mechanism, then probably that step is a fictional one. Like many other things on the book, I have found this advise very helpful and often saved me from committing a grave mistakes on paper. I figured this 'rule' must also extend to other cases of reaction mechanisms and not only to pericyclic reactions.  I have noticed it is easy to identify things if we name them. So I am gonna call this the rule of classified mechanisms . Don't judge, no one said I am an expert on naming things. (I originally thought of calling it the "Grossman's Rule" but that is already exists in the book) As organometallic chemistry is synthetically versatile and widely used in research, I planned to have a small page consisting all the valid reaction mechanism steps  at one place. So any step you write while doing a o...

Electrochemically Driven Desaturation (EDD) Electrochemistry has l ong been ignored in synthetic organic chemistry despite having extraordinary potential (pun intended). Although many large industrial processes are electrochemical, when it comes to organic chemistry, things can get pretty complicated and often the reproducibilty becomes an issue. This is mainly due a lack of standard. But since the unveiling of ElectraSyn 2.0 by IKA in 2017 the community got hold of a robust medium to carry out reproducible electrochemical transformations. Since then the applications of electrochemistry have been continuously increasing in organic synthesis and often exciting reactions are being discovered.  This very recent article by Baran group at Scripps Research Institute, California, is an excellent example of an electrochemically driven chemical transformation known as Desaturation (EDD). Desaturation is the reverse of hydrogenation of α,β-unsaturated carbonyl compounds where two ...

Prostaglandins are a class of molecules that helps regulate many physiological activities inside the body. Derivatives of prostaglandin and analogues are used heavily in pharmaceuticals for various uses. an analogue of PGF2α, latanoprost, is used in the treatment of glaucoma, and is a billion-dollar drug as of 2010. However, their synthesis requires many steps and generates a lot of waste .  Back in 1969, E J Corey developed a 17 steps synthesis of Prostaglandin F2α and that was the preferred route for a long time, simply because there was no other better route. But in 2012, Varinder Aggarwal and his group reported a 7 step synthesis of PGF2α which uses a proline catalysed aldol reaction cascade.  Aggarwal's retrosynthesis of PGF2α By using succinaldehyde as a simple starting material, the crucial intermediate 7  can be accessed, which contains 2 of the 4 stereocenters of PGF2α. This incredible transformation is a proline-catalyzed enantioselective aldol condensatio...

There was a time when completing the synthesis of a complex target molecule was a big deal, no matter the yield and waste and the number of steps involved. However, today, 20 years into the twenty first century, the value of a total synthesis totally depends the overall yield and waste management of  the process and how short and green the synthesis is. (I am assuming you are at least little bit familiar with total synthesis, at least the concept of it. In case this sounds new to you feel free to quickly get an idea here and check out my earlier post on the blog). This article in Chemical Society Reviews appeared a decade ago authored by Newhouse, Hoffmann and Baran , and discusses the crucial aspect of 'economy' in natural product synthesis. They argue that improving the three economies of synthesis  should be the goal of a synthetic chemist in achieving a practical route to the target molecule. This is darn exciting because there are not many papers that deal wit...

The article opens with the line " Reactions that couple two aromatic rings to make biaryls are among the most widely used processes in the pharmaceutical industry " and brings us to the problem that whereas metal-catalyzed cross coupling has found wide success in constructing biaryl rings, it has not been that successful in heterobiaryl construction . So, the authors established to do the same, get this, by avoiding metals all together. Now, personally for me, this is a hell lot exciting because I want to see more synthetic chemistry that exclude metals . It is very true that metals, especially transition metals still dominates both academics and especially industry in cross-coupling, metathesis and asymmetric catalysis reactions. But that does not diminish the facts that they still posses a threat to the environment (heavy metals), they are costly and they are rare, making them going against a green, economic development in chemistry. But. only one property tri...