Boron in aromatic molecules

Here’s my Monday, October 7, 2013’s two cool facts about boron heterocycles.

First of all, boron is tricky and it is not always obvious which factors control stability. Take, for instance, a recent theoretical JACS paper by Professor Roald Hoffmann of Cornell University. The manuscript contains a lot of very interesting data on boron heterocycles and is, in many ways, a call to arms for those who are interested in this subject. However, how would you predict the whopping 24 kcal/mol difference in stability (calculated relative energies) between the following two molecules? I realize they are not the same, but 24 kcal/mol? This means that NBN motifs are special…

A lot of really imaginative work in the area of aromatic boron heterocycles has been done by Prof. Liu of Boston College (formerly of the University of Oregon). I am not going to say anything about his nice synthesis of aromatic boron-containing heterocycles. Instead, I will focus on properties and showcase a co-crystal structure between azaborine and T4 lysozyme. The hydrophobic cavity of this enzyme accepted azaborine, a view of which I made using PyMol (pdb code 3hh3, below). It can be clearly seen that the azaborine molecule binds in two conformations which relate to each other by way of a “flip”. Given the amount of aryl groups in biologically active molecules, these boron heterocycles are certainly interesting! How about using them as fragments? Someone should…