Conformationally constrained pyrrolidines

In 2009 Mayr et al. demonstrated experimentally that electrostatic activation was indeed responsible for the more than 10 -fold acceleration in the asymmetric cyclopropanation reaction of the 38-derived zwitterion with sulfur ylides, as well as for the high stereoselectivity of this reaction.  

After the rediscovery of (S )-proline-catalysed reactions in 2000 and the discovery of the outstandingly efficient family of Jorgensen-Hayashi s catalysts in 2005, many research groups around the world have struggled in the search for different and more efficient chiral amino-catalysts, based on the pyrrolidine scaffold. A huge number of steric and electronic structural variations have been proposed along the way, sometimes resulting in the 

Engqvist, J. Casas, H. Sunden, I. Ibrahem and A. Cordova, Tetrahedron Lett., 2005, 46, 2053. 

Calderon, R. Fernandez, F. Sanchez and A. Femandez-Mayoralas, Adv. Synth. Catal, 2005, 347, 1395. 

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Sequential pyrrolidine and hydantoin ring-forming reactions via intramolecular [2+3] cycloaddition have been applied to the stereoselective solid-phase synthesis of conformationally constrained tricyclic triazacyclopenta [C]pentalene scaffold 43 < 1999JOC8342>. These novel compounds 43 share the structural complexity characteristic of certain alkaloid natural products, angular triquinanes. The retrosynthetic analysis is shown in Scheme 87. 

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