Catalyst cleans up alcohol couplings
Eight years’ work yields Mitsunobu chemistry with nothing but water as a byproduct
UK researchers have updated a key reaction in the chemistry toolkit, making nucleophilic substitution reactions of alcohols cleaner than ever. Currently, the best Mitsunobu coupling processes have moved on from using stoichiometric amounts of phosphine and azo compounds (and producing corresponding amounts of phosphine oxide and hydrazine waste), to using these reagents in catalytic amounts. However, these catalysts must cycle between oxidised and reduced forms, and therefore need large amounts of oxidants and reductants that are compatible with each other in the reaction mixture.
Now, a team led by Ross Denton at the University of Nottingham has designed a phosphine oxide catalyst that doesn’t need oxidants or reductants, and dispenses with the azo reagent entirely, producing water as the only byproduct.