I flew into Boston last night and had a great time at the Chemistry Department (Boston University) earlier today. A special thanks goes to Professor Aaron Beeler, my main host, who is running an innovative program in flow synthesis, bioactive molecule synthesis, and reaction discovery at BU (http://www.bu.edu/chemistry/faculty/beeler/). I met Aaron last Summer at the Gordon Conference on High-Throughput Chemistry and Biology, where he invited me to visit his storied department. I just came back from our dinner at the Eastern Standard (awesome oysters there, ladies and gentlemen) with Aaron and Professor Scott Schaus. While we were having our drinks at this fine establishment, I kept thinking about the significance of much smaller amounts of alcohol. Sounds like an oxymoron, I know… What I mean is this: while talking to Scott earlier in the day, I was reminded about the significance of achiral additives in asymmetric catalysis. Below is a link to the Angewandte paper by Scott, who discovered a superb ketone allylation process and spent several years perfecting this catalysis.
The pre-2009 mechanistic work by the Schaus lab showed step A to be rate-limiting. The rate order in alcohol was not established at that time. One could logically assume this additive to have an inhibiting effect on the reaction. An important insight offered by the 2009 study is that the rate-determining ligand exchange process is in fact not the initial formation of the active boronate species (step A), but the liberation of the catalyst from allylation product (step B). Check out the role of the tert-butanol additive (Figure 2) on the reaction! This nice work also reminded me of the old review by Shibasaki pointing to the significance of ACHIRAL additives in ASYMMETRIC catalysis. I think we should spend way more attention to the effect of such species. Here is a link to the Shibasaki review:
Ok, I am off to bed – catching a 6am flight back to Toronto, where I am giving two lectures in my graduate class and second year organic class tomorrow… Thankfully my student Adam filled in for my CHM 249 class today!