04 October 2023
Apex Chemistry Blog


Author: Dr Frédéric Beltran

Download a copy of the article here

Over the last four decades, Samarium iodide (SmI2, Kagan’s reagent) has been extensively used as a single-electron transfer (SET) reagent. “Unfortunately, SmI2 must almost always be used in significant excess, thus raising issues of cost and waste.”1 Of the few reports utilising catalytic SmI2, all require the use of a super-stoichiometric amount of a metal co-reductant (magnesium, zinc amalgam, mischmetal), additives (TMSOTf, TMSCl) or electrochemistry (samarium electrodes) to achieve a turnover and regenerate Sm(II). Until recently, these systems remained state of the art.

In recent years, the Procter group has demonstrated the possibility of using solely sub-stoichiometric amounts of SmI2 to catalyse radical cyclisation cascades to produce complex polycyclic scaffolds. The recent methods developed by the group rely on a radical-relay approach, with a careful design of the reaction mechanism, that eliminates the need for a co-reductant or additives.


The initial intramolecular SmI2-catalysed radical cyclisation cascades reported by Procter and co-workers operated with SmI2 loadings as low as 5 mol% and delivered complex polycyclic products containing up to four stereocentres, in high yields and typically with good diastereocontrol.1,2


The spring-loaded nature of the cyclopropyl substituted ketone 1 is the key to the catalytic radical process. This transformation starts with a reversible SET from Sm(II) to the substrate 1 to produce a ketyl radical 2 which fragments, by cyclopropyl-ring opening, to give an enolate radical 3. Subsequent intramolecular cyclisation, with the pendant alkyne or alkene acting as a radical trap, generates a new radical 4, which rebounds by addition to the Sm(III)-enolate, thus generating a new ketyl radical 5. Back electron transfer to Sm(III) regenerates the SmI2 catalyst and liberates the product 6. Furthermore, dearomatizing radical cyclisations were also successful using heteroarene substrates as the radical acceptor.



A more challenging intermolecular cross-coupling of cyclopropyl ketones 7 and alkynes 8, using the SmI2-catalysed radical-relay approach, was successfully performed for the construction of decorated cyclopentenes 9.3

More recently, applying the SmI2-catalysed approach to spring-loaded bicyclo[1.1.0]butyl ketones 10 and electron-deficient alkenes 11 allowed for the synthesis of bicyclo[2.1.1]hexanes 12, with a high-profile role as saturated bioisosteres of substituted benzenes in medicinal chemistry.4




  1. H.-M. Huang, J. J. W. McDouall, D. J. Procter, Nature Catalysis 2019, 2, 211-218.
  2. H.-M. Huang, Q. He, D. J. Procter, Synlett 2020, 31, 45-50.
  3. S. Agasti, N. A. Beattie, J. J. W. McDouall, D. J. Procter, J. Am. Chem. Soc. 2021, 143, 3655-3661.
  4. S. Agasti, F. Beltran, E. Pye, N. Kaltsoyannis, G. E. M. Crisenza, D. J. Procter, Nature Chemistry 2023, 15, 535-541.

    Make an enquiry

    Send us your details, and one of
    our expert team will be in touch