Switching Pathways: Room-Temperature Neutral Solvolysis and Substitution of Amides


  • We thank AstraZeneca and the EPSRC for the joint organic studentship initiative (M.H.) and the EPSRC for a grant to K.I.B.-M. and C.E.H (grant number EP/G036764/1). G.C.L.-J. is holder of a Royal Society Wolfson Research Merit Award.


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Stick or twist: By introducing steric hindrance at the nitrogen atom, stable linear amides bearing an electron-withdrawing α-substituent (Z=Ar, PhSO2, P(O)(OR)2, CN, or CO2R) can be induced to undergo solvolysis and substitution reactions through an elimination–addition mechanism (see picture). Key to this process is a low barrier to rotation around the amide bond and the α-substituent Z.