Synthesis of Highly Functionalized 12-Membered Trifluoromethyl Heterocycles via a Nondecarboxylative Pd-Catalyzed [6 + 6] Annulation

An efficient method for the construction of 12-membered heterocycles with a trifluoromethyl group (3) was achieved via a nondecarboxylative Pd-catalyzed [6 + 6] annulation of six-membered trifluoromethyl benzo­[d]­[1,3]­oxazinones (1) with four-membered vinyl oxetanes (2). A variety of relatively large heterocycles 3 featuring a stereogenic trifluoromethylated carbon center, an amino group, as well as an alkenyl and a carbonate moiety were obtained. An X-ray crystallographic analysis revealed a unique 3D architecture of the products that affords an attractive chemical space. Whereas the method can be applicable for nonfluorinated substrates, the trifluoromethyl group plays a vital role in this unexpected Pd-catalyzed nondecarboxylative ring expansion.