Art of Synthesis

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...

Yesterday, a Co-catalyzed enantioselective hydrogenation  of α,β- unsaturated carboxylic acid has been  published in nature communication. This is important because although the metal catalyzed hydrogenations are well-established ( Noyori hydrogenation won the Nobel in 2001), most of them uses rare earth metals such as Rh, Ir and Ru. These metals, while having found great uses in catalysis, are not so great in terms of economy and green chemistry. Whereas Cobalt is earth abundant  and less toxic. The optimum ligand used is (S,S)-Ph-BPE, not some complicated system. and the reaction uses 40 atm pressure of hydrogen gas in methanol solvent with Zn additive. Zn additive presumably helps in activating the pre-catalyst and suppresses the deactivation of the active catalyst. The excellence lies in the high yield and high ee achieved by this reaction. All yields are >80% and all but one ee are  >90% with most being >96% as reported in the sub...