DOI: 10.1002/chem.200901433 Michael Addition Initiated Carbocyclization Sequences with Nitroolefins for the Stereoselective Synthesis of Functionalized Heterocyclic and Carbocyclic Systems Estelle Dumez, Anne-Catherine Durand, Martial Guillaume, Pierre-Yves Roger, Robert Faure, Jean-Marc Pons, Gatan Herbette, Jean-Pierre Dulcre, Damien Bonne,* and Jean Rodriguez* [a] Introduction Heterocycles and carbocycles are key structural features in many biologically significant compounds. For example, tetra- hydrofuran and -pyran skeletons are found in several inter- mediates for the synthesis of numerous polyethers and iono- phore natural products. [1] Interesting biological activities are exhibited by several polysubstituted pyrrolidines. [2] Among carbocycles, five-membered rings are particularly important building blocks for the synthesis of natural products, for ex- ample, the prostaglandins. [3] Therefore, the development of highly stereoselective reactions for the synthesis of function- alized cyclopentane derivatives remains an important goal in organic synthesis. [3e] Moreover, the presence of an unsaturated bond available for further elaboration has stimulated interest in a plethora of synthetic routes to 3-methylene tetrahydrofurans, [4] as well as methylene cyclopentanes. [5] For the construction of these motifs, two major five-membered ring-forming pro- cesses have been developed in recent years. Although the transition-metal-catalyzed cycloisomerization of 1,6-dienes represents an extremely powerful method for the rapid as- sembly of carbo- and heterocyclic compounds, [6] considera- ble attention has recently focused on [3 + 2] annulations, [3a, 7] due to the advantage of creating two carbon–carbon or het- eroatom–carbon bonds under the same reaction conditions. Alternatively, regio- and stereoselective cyclizations can be achieved by intramolecular 1,3-dipolar cycloadditions, [8] usually for the construction of five-membered heterocycles. Indeed, two rings are generated during these cycloadditions, one of which is a five-membered heterocycle that can be cleaved, thereby leading to the formation of either a carbo- or a heterocycle, stereospecifically substituted by two new functional groups. [9] As part of our sustained interest in one-pot diastereose- lective cyclizations, we reported some years ago straightfor- ward entries to functionalized carbocycles and heterocycles, provided by the Michael addition–intramolecular carbocycli- zation reaction between unsaturated nucleophiles and a,b- disubstituted nitroalkenes. [10] Very recently, we reported an asymmetric version of this efficient sequence that allows the Keywords: cyclization · cycloaddition · domino reactions · Michael addition · nitroolefins Abstract: The synthesis of various heterocycles and carbocycles (tetrahydrofurans, pyrrolidines, cyclopentanes) has been achieved by using new and efficient ionic ad- dition/cyclization sequences. Nitroolefins play an important role in the Michael ad- dition induced ring-closing reactions (MIRC) reported in the present article, with various substituted alcohols, amines, Grignard reactants, or malonate derivatives acting as the nucleophile partner. The optimized cascade reactions were high yield- ing in most cases and highly stereoselective, creating up to three stereogenic cen- ters starting from achiral substrates. [a] Dr. E. Dumez, Dr. A.-C. Durand, Dr.M. Guillaume, Dr. P.-Y. Roger, Dr. R. Faure, Dr. J.-M. Pons, Dr. G. Herbette, Dr.J.-P. Dulcre, Dr. D. Bonne, Dr. J. Rodriguez Aix-Marseille UniversitØ Institut des Sciences MolØculaires de Marseille iSm2 CNRS UMR 6263, Centre Saint JØrôme service 531-13397 Marseille Cedex 20 (France) Fax: (+ 33) 491-288-841 E-mail : jean.rodriguez@univ-cezanne.fr damien.bonne@univ-cezanne.fr Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.200901433.  2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Chem. Eur. J. 2009, 15, 12470 – 12488 12470