Intermolecular Cross-Double-Michael Addition between Nitro and Carbonyl Activated Olefins as a New Approach in C-C Bond Formation Xiaohua Sun, ² Sujata Sengupta, ² Jeffrey L. Petersen, ² Hong Wang, ‡ James P. Lewis, ‡ and Xiaodong Shi* ,² C. Eugene Bennett Department of Chemistry and Department of Physics, West Virginia UniVersity, Morgantown, West Virginia 26506 xiaodong.shi@mail.wVu.edu Received August 21, 2007 ABSTRACT A novel intermolecular cross-double-Michael addition between nitro and carbonyl activated olefins has been developed through Lewis base catalysis. The reaction took place with a large group of -alkyl nitroalkenes and r,-unsaturated ketone/esters, producing an allylic nitro compound in good to excellent yields. Efficient C-C bond formation and implementation of diverse functionality are two crucial aspects in organic synthesis. 1 In the last two decades, tandem (or cascade or sequential) reactions of designated precursors brought great attention to the construction of complicated organic molecules. 2 Signifi- cant progress has been made using this strategy in the total synthesis of natural products and biological activated mol- ecules. 3 Meanwhile, intermolecular sequential reactions across different reactants have been developed into many powerful methodologies, including the Mannich reaction, 4 the Baylis-Hillman reaction, 5 and the Robinson annulations, 6 etc. The fact that tandem reactions of different substrates can rapidly combine organic functionalities within “one step” provides undeniable benefits as a simple, efficient, and atom- economical approach in organic synthesis. Our interests in developing new organic reactions with the capability of rapid functional group construction origi- nated from the Lewis base (LB) mediated Baylis-Hillman reaction (reaction A). As shown in reaction B, the successful intermolecular cross-double-Michael addition will lead to very attractive products in one step and provide a highly efficient novel methodology in complex molecule synthesis. According to the literature, the only successful example using this strategy is the homodimerization of enones by ² C. Eugene Bennett Department of Chemistry. ‡ Department of Physics. (1) (a) Corey, E. J. Angew. Chem., Int. Ed. 1991, 30, 455-465. (b) Chemler, S. R.; Trauner, D.; Danishefsky, S. J. Angew. Chem., Int. Ed. 2001, 40, 4544-4568. (c) Trost, B. M.; Toste, F. D.; Pinkerton, A. B. Chem. ReV. 2001, 101, 2067-2096. (d) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem., Int. Ed. 2005, 44, 4442-4489. (2) (a) Nicolaou, K. C.; Montagnon, T.; Snyder, S. A. Chem. Commun. 2003, 551-564. (b) Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. G. Angew. Chem., Int. Ed. 2006, 45, 7134-7186. (3) (a) Zu, L. S.; Wang, J.; Li, H.; Xie, H. X.; Jiang, W.; Wang, W. J. Am. Chem. Soc. 2007, 129, 1036-1037. (b) Nicolaou, K. C.; Lim, Y. H.; Piper, J. L.; Papageorgiou, C. D. J. Am. Chem. Soc. 2007, 129, 4001- 4013. (c) Baran, P. S.; Maimone, T. J.; Richter, J. M. Nature 2007, 446, 404-408. ORGANIC LETTERS 2007 Vol. 9, No. 22 4495-4498 10.1021/ol702059x CCC: $37.00 © 2007 American Chemical Society Published on Web 10/02/2007