Lactone Reduction Using Samarium Diiodide: Biocatalysis, Radical Cyclisations and Ester Migration

  • Charlotte Morrill

Student thesis: Phd


Samarium diiodide (SmI2, Kagan's reagent) has shown itself to be a highly versatile reducing agent since its introduction to the synthetic community in 1977. Although SmI2 was initially thought to be unable to reduce carboxylic acid derivatives, the discovery and development of the SmI2-H2O reagent system has rendered such reactivity possible and has opened new avenues for exploration. The reductive cyclisation of six-membered lactone substrates has previously been reported by the Procter group. Herein, the analogous cyclisations of five-membered lactones, substrates which exhibit lower reactivity towards Sm(II), are described. By the use of appropriate additives, such lactones can be used to access substituted cyclohexanone motifs through diastereoselective radical cyclisation. A synthetic route towards enantiomerically enriched cycloheptan- and cyclooctanols, structural motifs present in various biologically relevant molecules, is also disclosed. The strategy exploits Baeyer-Villiger monooxygenase-mediated biocatalysis in order to access lactone substrates with high enantioenrichment. A kinetic resolution process which transforms cyclic ketones bearing α-quaternary stereocentres into the corresponding lactones has been developed. The products of the kinetic resolution are suitable substrates for diastereoselective Sm(II)-mediated cyclisations. Overall the process gives access to diverse enantiomerically enriched carbocyclic scaffolds from simple racemic starting materials. Finally, a novel reactivity mode of Sm(II) is reported, with the development of a 1,4-ester migration. The reaction proceeds through an unusual radical species formed at an acyclic ester moiety, rather than at the lactone carbonyl as observed in previous work. The reactivity appears to be determined by the conformation of the lactone substrate, where an alkyl substituent at the 5-position plays a key role in determining lactone conformation and thus the course of the reaction.
Date of Award1 Aug 2020
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorDavid Procter (Supervisor) & Nicholas Turner (Supervisor)


  • radical
  • lactone
  • samarium
  • biocatalysis

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