Perhaps the best-known ring-expansion reaction is the Baeyer-Villiger oxidation, first reported in 1899- not surprisingly by Adolf von Bayer and Victor Villiger. As we’re all aware, reaction of a carbonyl with a peracid generates a Criegee-type intermediate that undergoes rate-limiting concerted rearrangement to form an ester or lactone. The migration order is substituent dependant, with

The first electrophilc aromatic substitution reaction you were taught as an undergraduate was almost certainly nitration.1 Nitration and subsequent reduction of the aryl nitro group to an aniline via high temperature metal catalysed hydrogenation remains an important industrial process. The reduction has many flavours- both in terms of the substitution pattern on the aryl (and

The ability to handle gaseous reagents presents a number of challenges for synthetic chemists. The problem becomes particularly acute when scaling up biphasic (liquid/gas) or even triphasic (gas/liquid/solid) systems due to limiting mass transfer effects. Pressure vessels or autoclaves are also not always practical and easy to come by. A practical solution to this (if

Many years ago, I heard an anecdote regarding a fortuitous discovery in the Sharpless lab. A graduate student had been awarded their PhD and the group were celebrating in the lab with bottles of red wine (I know- but they were different times). Someone in the group-who had obviously consumed a sufficient quantity of the

In March 1989, two chemists, Stanley Pons and Martin Fleishmann, stunned the world by claiming that an electrical current from a palladium electrode immersed in a test tube of water had resulted in nuclear ‘cold fusion’ at room temperature.1 For many years, attempts to understand and reproduce this seemingly impossible result- with sketchy information from

Back in August I posted a scheme for the synthesis of a late-stage intermediate towards PF-06826647, a compound identified by Pfizer as a potent and selective tyrosine kinase 2 (TYK-2) inhibitor. I asked if you could identify reagents or intermediates A, B and D. Below are the answers! You can read more here in the full

The scheme below shows the synthesis of a late-stage intermediate towards PF-06826647, a compound identified by Pfizer as a potent and selective tyrosine kinase 2 (TYK-2) inhibitor that has entered phase 2 clinical trials for the treatment of autoimmune diseases. Can you identify intermediates A, B and D? Answers and a reference will be posted

Last month I posted a scheme for the synthesis of a late-stage intermediate towards AZD9833, a compound identified by AstraZeneca as a selective estrogen receptor degrader (SERD) and antagonist that is currently in phase 2b clinical trials for the treatment of ER+ breast cancer. I asked if you could identify reagents or intermediates A-C. Below are

It’s not often that drug molecules find themselves on the reagent shelf alongside materials that may have been used to assemble them. The prince and the pauper so to speak. In 2019 Paul Hergenrother from the University of Illinois published a paper in Angewandte Chemie claiming a diazomethane surrogate that was a commercially available, weighable, solid:

A couple of interesting papers published recently on aryl iodination. I sure I don’t need to reiterate how useful iodinated intermediates are in synthesis- most significantly their heightened reactivity in metal catalysed cross coupling chemistry,1 and, more recently their application as organocatalysts in hypervalent iodine chemistry.2 As is common in synthetic science, the intermediates you