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

Sabrina Touchet (1) , Callum Yeardley (2) , Charles O’hara (2) , Philippe Gros (1)

1 L2CM - Laboratoire Lorrain de Chimie Moléculaire
2 University of Strathclyde [Glasgow]

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.

Domaines: Chimie organique

Sabrina Touchet, Callum Yeardley, Charles O’hara, Philippe Gros. Critical ligand and salt effects in organomagnesiate‐promoted 3,3‐disubstituted phthalides synthesis from 2‐iodobenzoate derivatives. European Journal of Organic Chemistry, 2021, 2021 (34), pp.4835-4845. ⟨10.1002/ejoc.202100899⟩. ⟨hal-03325715v1⟩