Synfacts 2019; 15(11): 1299
DOI: 10.1055/s-0039-1691045
Organo- and Biocatalysis
© Georg Thieme Verlag Stuttgart · New York

A Newly Designed Catalyst for Additive-Free Mitsunobu Reactions

Benjamin List
Benjamin Mitschke
Beddoe RH, Andrews KG, Magné V, Cuthbertson JD, Saska J, Shannon-Little AL, Shanahan SE, Sneddon HF, Denton RM. * University of Nottingham, Jealott’s Hill International Research Centre, and GlaxoSmithKline Medicines Research Centre, Stevenage, UK
Redox-Neutral Organocatalytic Mitsunobu Reactions.

Science 2019;
365: 910-914
Further Information

Publication History

Publication Date:
18 October 2019 (online)



The Denton group reports a redox-neutral P(V)-catalyzed Mitsunobu reaction. Upon activation by dehydration, the newly designed phosphine oxide catalyst is converted into the corresponding dihydrobenzoxaphospholium ion, which activates an alcohol for nucleophilic attack. By this method, a variety of sufficiently acidic nucleophiles gave the corresponding substitution products in moderate to very good yields with almost complete inversion of configuration.



Mitsunobu reactions are redox condensations that are among the most valuable organic transformations because of their high degree of reliability and stereospecificity. However, they are also generally wasteful. The development of this completely catalytic version not only overcomes problems such as the use of toxic diazo compounds or the production of phosphine oxide waste, but also avoids the use of additional oxidants or reductants by operating exclusively in the P(V) regime. An orthogonal activation mode of the catalyst to permit the use of less-acidic nucleophiles would expand the generality of this method.