Ligands Dial In Ring Size

Varying the ligand in a particular palladium-catalyzed cyclization reaction gives chemists access to four different types of heterocycles, with five-, six-, or seven-membered rings, Stephen L. Buchwald and Dmitry Tsvelikhovsky of Massachusetts Institute of Technology report (J. Am. Chem. Soc. 2010, 132, 14048). The researchers found that they could efficiently prepare indoles, carbazoles, acridines, and dibenzazepines from a common diphenylamine precursor (shown, center), synthesized from the condensation of 2-bromostyrene and 2-chloroaniline derivatives, just by altering the ligand used in the intramolecular heterocyclization. Although the transformations provide routes to myriad molecules, of particular interest is the seven-membered ring dibenzazepine (shown, right), which formed when the phosphino-amino biphenyl ligand known as DavePhos was used. The dibenzazepine skeleton is the core structure in mood-stabilizing drugs, such as carbamazepine and oxcarbazepine, which are molecules currently prepared by a gas-phase dehydrogenation of iminobibenzyls at high temperatures. “To the best of our knowledge, our results represent the first cases of such intramolecular reactions that incorporate a 7-endo cyclization,” the researchers note.