Critical ligand and salt effects in organomagnesiate-promoted 3,3-disubstituted phthalides synthesis from 2-iodobenzoate derivatives

Sabrina Touchet, Callum Yeardley, Charles T. O'Hara, Philippe C. Gros

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3 Citations (Scopus)
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Abstract

Phthalides, also called isobenzofuranones, are widespread in many biologically active compounds and natural products. To date, most of their synthetic routes are non-convergent. Herein we report a convergent route using a metal halogen exchange (MHE) strategy. Indeed MHE of easily available 2-iodobenzoate derivatives, using the bimetallic organomagnesiate complex (rac)-(BIPHEN)BuMgLi, where (rac)-BIPHEN is (rac)-5,5′,6,6′-tetramethyl-3,3′-di-t-butyl-1,1′-biphenyl-2,2′-diol, followed by addition of a ketone which lead to an intramolecular cyclisation, and the formation of a series of diverse 3,3-disubstituted isobenzofuranones in good yield. Among the several MHE agents investigated, (rac)-(BIPHEN)BuMgLi was the only one to make such a process possible with full tolerance of various reactive functional substituents useful for subsequent transformations. The synthetic pathway to access the magnesiate has been found to play a prominent role in its reactivity. Therefore, the bimetallic magnesiate complex has been characterized by solution-state 1H, 7Li and 1H DOSY NMR experiments.
Original languageEnglish
Pages (from-to)4835-4845
Number of pages11
JournalEuropean Journal of Organic Chemistry
Volume2021
Issue number34
Early online date18 Aug 2021
DOIs
Publication statusPublished - 14 Sept 2021

Funding

The authors would like to thank Fran?ois Dupire (UMR 7053?L2CM) and Fabien Lachaud (UMR 7053?L2CM) for the HRMS and GC-MS experiments and related discussions. We gratefully acknowledge the support of the Royal Society (IEC\R2\170207) and the Leverhulme Trust (RPG-2016-281) for funding. They thank also the Universit? de Lorraine, the CNRS and the University of Strathclyde for their support. Data associated with this study can be accessed at https://doi.org/10.15129/4c342ff2-8f1f-4a69-aad4-ff2f93cff686. The authors would like to thank François Dupire (UMR 7053–L2CM) and Fabien Lachaud (UMR 7053–L2CM) for the HRMS and GC‐MS experiments and related discussions. We gratefully acknowledge the support of the Royal Society (IEC\R2\170207) and the Leverhulme Trust (RPG‐2016‐281) for funding. They thank also the Université de Lorraine, the CNRS and the University of Strathclyde for their support. Data associated with this study can be accessed at https://doi.org/10.15129/4c342ff2‐8f1f‐4a69‐aad4‐ff2f93cff686.

Keywords

  • BIPHEN-H2
  • cyclization
  • lactones
  • magnesiate
  • metal-halogen exchange

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