Lewis acids in water (another classic)

As I prepare my lectures for the second year organic chemistry class, I can’t help but wonder about a good way of teaching Lewis acid/base chemistry. When our students learn about the likes of AlBrfor the first time, they get used to the idea that Lewis acids are, by their very nature, water-sensitive compounds. There is no doubt that the vast majority of “traditional” Lewis acids do not respond well even to trace amounts of water. In fact, the notion of water-tolerant Lewis acids would have been a heresy even 20 years ago. But things have changed. When I talk about the “next-gen” Lewis acids, I always point to the classic work of Kobayashi, particularly to his insightful JACS paper from 1998. In it, Kobayashi has taught us all a valuable lesson in achieving the balance of thermodynamic and kinetic factors in regards to Lewis acidity.

If the key parameters (the so-called water exchange rate constant (WERC) and hydrolysis constant) are chosen properly, a metal-based salt could turn into an excellent Lewis acid even in the presence of water. What takes place between a given metal salt and water is substitution of inner-sphere water ligands. To have a Lewis acid catalyst in water, all you need to do is tone down your metal’s affinity to water, while keeping water exchange rate constant high. If the stars are aligned properly, the resulting compound will have a chance to be a water-tolerant Lewis acid. It makes perfect sense: in an aqueous environment, metal salts would undergo exchange reactions of their water ligands. If the substrate you want to activate exists in the system, it can coordinate to the metal cation instead of the water molecule, resulting in Lewis acid activation. Rational, parameter-driven choice of reagents is relatively rare in synthesis, which makes this classic Kobayashi’s paper particularly important.

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http://pubs.acs.org/doi/pdf/10.1021/ja980715q

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