Epoxides in dearomatization

I think most of us are aware of the delightful selectivity with which nature’s p450 enzymes turn benzene derivatives into dearomatized structures. For instance, p450’s are known for the conversion of aromatics into highly reactive monoepoxides, whereas the enzymes of pseudomonas putida take on aromatic compounds and convert them into cis-diols with exquisite selectivity.

I was looking at these reactions, noting that these oxidations affect two ring atoms at a time. What about turning an aromatic ring into an exocyclic epoxide structure in which one of the carbon atoms is outside the ring? There is in fact a great and purely synthetic way of running this transformation. I refer to the Adler-Becker reaction. It constitutes an enormously empowering, although not often used, process. The reaction does require a fairly electron-rich aromatic phenol, but the complexity generated in the course of the process is second to none. Professor Jon Njardarson of the University of Arizona used it in his approach to vinigrol and, although this was ultimately a failed route, the idea was really interesting. While in Colorado last week, I saw this process put to great use by Professor Derek Tan of the Sloan-Kettering Institute in New York City in an approach to medium-sized rings. What’s most interesting about Derek’s way is that he was later able to cleave the epoxide C-C bond, which is rather uncommon. I will discuss this nice work at some point.