2,3-methanopyrrolidines: Synthesis and ring-opening transformations

New methods for the preparation of 2-azabicyclo[3.1.0]hexane compounds (2,3- methanopyrrolidines) have been developed over the past three decades. Once viewed as rather exotic molecules, they can now be considered as readily accessible, especially by intermolecular Simmons-Smith type reactions or by intramolecular titanium-mediated cyclopropanation (Kulinkovich-de Meijere reaction). Accordingly, a number of applications of these compounds have emerged: in particular, they are being used as mimics of pyrrolidine, piperidine or proline subunits for the development of novel bioactive molecules. The use of 2,3-methanopyrrolidines as precursors of more complex nitrogen-containing heterocyclic systems has also become a relevant idea. This chapter is organised in two sections: a brief review of the main methods of synthesis of 2,3-methanopyrrolidines is first presented. It is followed by a personal account of some of the transformation reactions that have been developed over the last fifteen years.