In the modern age of accessible quantum mechanics (DFT and so on), teaching hybridization can be anticlimactic. However, simple concepts continue to be empowering. In the past, I mentioned the “rabbit ear” view of carbonyl oxygen’s lone pairs. Despite the documented existence of n-to-π* interactions that cannot be adequately described using hybridization models, there are many cases where the good old bonding arguments hold and help understand molecular structure.
Today I want to talk about the often overlooked Bent’s rule. By the way, there is a great review by Professor Igor Alabugin of Florida State University in the J. Phys. Org. Chem. on this subject (see the link below). Bent’s rule states that “s-character concentrates in orbitals directed toward electropositive substituents or, alternatively, that atoms direct hybrid orbitals with more p-character towards more electronegative elements”. Here is a practical demonstration of its utility from Igor’s paper. Consider the molecule of difluoromethane. Chemical intuition based on electron repulsion might suggest that the F-C-F angle should be larger than the H-C-H angle. In reality, the opposite is true, which is a direct consequence of Bent’s rule. This is a fantastic example.
I have been travelling extensively, which is the reason for not being able to write any posts. Now the summerly pace is settling in and I am back in Toronto. Not too long ago, my graduate student Sean Liew brought up an interesting JACS manuscript to my attention. I asked Sean to sum it up and here is his take:
“When we consider the fundamental properties of water, hydride formation to furnish H– and HO+ is not the first thing that comes to mind. Prof. Benjamin Stokes at UC Merced just published a creative strategy for transfer hydrogenation of alkenes using water in the presence of palladium and tetrahydroxydiboron. The authors propose a mechanism in which the oxidative addition product of palladium and tetrahydroxydiboron allows for the recruitment of water molecules to the Lewis acidic boron ligands. This zwitterionic Pd-B-O-H complex can be likened to that of the very well known Pd-C-C-H moiety that is notorious for β-hydride elimination chemistry. The reaction appears to proceed through generation of boric acid and the active palladium hydride species that recruits the alkene or alkyne for migratory insertion. Repeat the water recruitment process with the other boron centre followed by reductive elimination provides the hydrogenated product. So why is this so intriguing? H-O+-B–-Pd species is just being deprotonated, but by way of the unique reactivity of this short-lived intermediate, water’s proton is turned into a hydride through an entirely “inorganic” β-hydride elimination process.”
You might have noticed a certain trend in contemporary approaches to mechanistic investigations using computation: the (over)use of water. It is curious that 10 years ago people rarely considered water and now it is the fixture of almost every other paper, seemingly to patch holes in mechanistic arguments.
Jokes aside, molecular-level involvement of adventitious molecules is an interesting topic. Of course, experiment is the “real deal” and I pay attention to studies that reveal strange rate laws that hint at solvent involvement in transition state assemblies. Several days ago I came back from Halifax, Nova Scotia, where I heard a great talk by Joseph Moran of the University of Strasbourg. He described a system that reveals the enabling role of nitromethane in catalysis (http://pubs.acs.org/doi/abs/10.1021/jacs.5b06055). While listening to his talk, I took note of a peculiar paper by Berkessel, which is not something I was familiar with. In this work, there is experimental evidence for the involvement of 3 HFIP molecules in the rate-limiting step of olefin epoxidation. This reminds me of Ryan Hili’s studies of aziridine aldehyde dimers, where we always noted an important role of trifluoroethanol. However, our kinetic work has not allowed us to conclude that something remarkable was happening on a “molecular level”. In the Berkessel case, the kinetics clearly point at the involvement of 3 molecules of HFIP in the transition state. Do let me know if you are aware of other interesting cases that implicate adventitious molecules in rate-limiting steps.
The central role of heterocycles in modern chemical synthesis cannot be overestimated. Last week, I had a chance to appreciate the role of some of the fathers of modern approaches to heterocycle use and construction. As part of a trip to Germany (superbly organized by Professor Herbert Mayr) I visited the Ludwigs Maximilian University in Munich. The highlight of this trip was a meeting with the two gentlemen featured on the picture below. On my right hand side is Professor Wolfgang Steglich, the discoverer of DMAP (among many other things), while on my left side is Professor Rolf Huisgen. As the founder of dipolar cycloaddition chemistry, Professor Huisgen needs no introduction and I really want to wish him a happy 96th birthday, which will be celebrated on June 13.
My host, Professor Mayr (a former PhD student of Huisgen), continues to push the boundaries of chemical reactivity. I already mentioned his work in the past and I am glad that he continues to educate the chemistry community on how one can predict selective reactions between various functional groups. With the help of my students, we will soon be collaborating with Professor Mayr to better understand the reactivity trends of our own molecules. The Mayr scale has served as the go-to tool in teaching organic reactivity. The following contribution features what I call “the real rule of 5” and I enjoy discussing it with my students.