This begins a new series I’m starting (which will actually last a while, unlike the summer’s “forgotten reactions” series) in which I discuss the research of people I’m interested in at the grad schools I’m applying to. It’s both to help myself in writing statements of purpose and to enlighten you, my readers, on what the future may hold for me. So…it’s pretty much all about me. 🙂
Anyway, the first installment of this series belongs to Dr. M. Christina White and her graduate student Ken Fraunhoffer at the University of Illinois, Urbana-Champaign. They have designed a diastereoselective synthesis of 1,2-aminoalcohols using a palladium(II)/sulfoxide catalyst that bypasses the oxygenation steps that have previously been necessary for allylic amination reactions. The first step is nucleophilic attack by a relatively weakly nucleophilic tosyl carbamate (the nucleophile must be weak enough to not attack the double bond directly). In the example the paper gives, this forms a five-membered ring with an exo vinyl group (thanks Balwin’s Rules! :-D). The vinyl group is transformed to COOH using some nasty RuCl3/NaIO4 condititons, and finally the ring breaks apart by reaction with sodium naphthalene, DME, and 6-M HCl, giving at last the desired 1,2-aminoalcohol.
Only an intramolecular version of the reaction has been studied so far, although White’s group is exploring the possibility of an intermolecular allylic amination. The worst stumbling block is the potential attack of a nucleophile directly on the double bond, instead of on the allylic carbon. Attaining the appropriate nucleophilicity for the aminating agent is key.