An Easy, Stereoselective Synthesis of Hexahydroisoindol-4-ones under Phosphine Catalysis

Deepti Duvvuru (1) , Jean-François Betzer (1) , Pascal Retailleau (1) , Gilles Frison (2) , Angela Marinetti (1)

1 ICSN - Institut de Chimie des Substances Naturelles
2 DCMR - Laboratoire des mécanismes réactionnels

A new synthetic approach to hexahydroisoindol-4-ones is reported, based on the formal [3+2] cyclization reaction between N-arylsulfonylimines and cyclic conjugated dienes, under phosphine catalysis. Key substrates are 3-vinylcyclohex-2-enones with electron-withdrawing substituents (ester, amido, cyano, phosphoryl and keto groups) on the exocyclic double bond, which afford the three atom synthons for the construction of the pyrroline ring. Total syn stereoselectivity is observed in these annulations. The scope of the reaction has been demonstrated and mechanistic issues are considered, based on deuteration experiments and DFT calculations.

Mots clés: phosphine organocatalysis; conjugated dienes; imines; hexahydroisoindolones; [3+2] annulations

Domaines: Catalyse; Chimie organique; Chimie théorique et/ou physique

Deepti Duvvuru, Jean-François Betzer, Pascal Retailleau, Gilles Frison, Angela Marinetti. An Easy, Stereoselective Synthesis of Hexahydroisoindol-4-ones under Phosphine Catalysis. Advanced Synthesis and Catalysis, 2011, 353 (2-3), pp.483-493. ⟨10.1002/adsc.201000701⟩. ⟨hal-00554156⟩