The CeCl3 Lewis Acid Promoter in the Stereoselective Construction of Carbon-Carbon Double Bonds

The presence of a C-C double bond in polyfunctionalized organic molecules is a crucial requirement for the control of its biologically activity.(1) The importance of having a site in the molecule that is able to generate geometrical isomerization of a carbon-carbon double bond stimulated the development of new olefination methodologies. In particular, some efforts focused on the ability of Lewis acids to provide a cheap alternative for the synthesis of molecules with C-C double bond in a highly stereoselective fashion. For several years, we have been investigating CeCl3 promoted organic reactions. This Lewis acid has been found to efficiently promote carbon-carbon (2) and carbon-heteroatom bond formation reactions.(3) In addition to being green in nature (4), CeCl3 has been widely used for both inter- and intramolecular reactions for the synthesis of organic molecules with significant biological importance. Regarding the total synthesis of biologically active small molecules containing a carbon-carbon double bond, we saw the possibility to employ CeCl3 in the stereoselective construction of 2,3- dihydropyridones 1,(5) and 1,2-dihydroquinolines 2.(6) The additional advantage of using CeCl3 in a reaction includes its selectivity and tolerance in the presence of other functional groups. For instance, it can be used during the functionalization of molecules at late stage involving complex molecules or undesirable use of protecting groups. Introduction of C-C double bonds, which are known to increase the activity in macrolides against bacterial RNA polymerase, is currently in progress in our laboratory. References: 1. Shen, X.; Nguyen, T. T.; Koh, M. J.; Xu, D.; Speed, A. W.; Schrock, R. R.; Hoveyda, A. H. Nature 2017, 541, 380-385. 2. Bartoli, G.; Marcolin, M.; Sambri, L.; Marcantoni, E. Chem. Rev. 2010, 110, 6104-6143. 3. Properzi, R. Marcantoni, E. Chem. Soc. Rev. 2014, 43, 779-791. 4. Cimarelli, C.; Di Nicola, M.; Diomedi, S.; Giovannini, R.; Hanprecht, D.; Properzi, R.; Sorana, F.; Marcantoni, E. Org. Biomol. Chem. 2015, 13, 11687-11695. 5. Bordi, S.; Cimarelli, C.; Lupidi, G.; Marsili, L.; Piermattei, P.; Marcantoni, E. J. Org. Chem. 2017, in preparation. 6. Cimarelli, C.; Bordi, S.; Piermattei, P.; Pellei, M.; Del Bello, F.; Marcantoni, E. Tetrahedron 2017, submitted.