Titanium-Mediated Cyclopropanation of Nitriles with Unsaturated Grignard Reagents: Application to the Synthesis of Constrained Lysine Derivatives

Gwénaël Forcher (1) , Nathalie Clousier (1) , Alice Beauseigneur (1) , Paul Setzer (1) , Fabien Boeda (1) , Morwenna Pearson-Long (1) , Philippe Karoyan (2, 3) , Jan Szymoniak (4) , Philippe Bertus (1)

1 IMMM - Institut des Molécules et Matériaux du Mans
2 UPMC - Université Pierre et Marie Curie - Paris 6
3 ENS-PSL - École normale supérieure - Paris
4 ICMR - Institut de Chimie Moléculaire de Reims - UMR 7312

A comparative study of the titanium-mediated cyclopropanation of (benzyloxy)acetonitrile and Boc-protected cyanohydrin using unsaturated Grignard reagents (but-3-enyl- and pent-4-enylmagnesium bromides) is described. The best conditions to provide the cis and trans isomers of cyclopropylamines bearing unsaturation were identified and the alkene moiety was subjected to chemical modifications, as shown by the synthesis of orthogonally protected cis- and trans-2,3-methanolysine, cis-2,3-methanoornithine, and cis-2,3-methanohomo­lysine.

Mots clés: amino acids; cyclopropane; Grignard reaction; nitriles; titanium

Domaines: Chimie organique

Gwénaël Forcher, Nathalie Clousier, Alice Beauseigneur, Paul Setzer, Fabien Boeda, et al.. Titanium-Mediated Cyclopropanation of Nitriles with Unsaturated Grignard Reagents: Application to the Synthesis of Constrained Lysine Derivatives. Synthesis: Journal of Synthetic Organic Chemistry, 2015, 47 (07), pp.992-1006. ⟨10.1055/s-0034-1379978⟩. ⟨hal-02132648⟩