Striking Alkenol Versus Allenol Reactivity: Metal-Catalyzed Chemodifferentiating Oxycyclization of Enallenols

An efficient chemodivergent metal-controlled methodology for the generation of different highly functionalized oxygen heterocycles from common enallenol substrates has been developed. Chemoselectivity control in the O?C functionalization of an enallenol can be achieved through the choice of catalyst: AuCl3, PdCl2, and [PtCl2(CH2?CH2)]2 exclusively afford dihydrofurans through selective activation of the allenol moiety, whereas FeCl3 solely gives tetrahydrofurans or tetrahydropyrans through selective activation of the alkenol moiety. We have also shown that a combination of metal-mediated hydroalkoxylation and allenic aminocyclization reactions can lead to a useful preparation of the tetrahydrofuro[3,2-b]piperidine core of the antimalarial alkaloid isofebrifugine. These divergent heterocyclization reactions have been developed experimentally and additionally, their mechanisms have been investigated by a theoretical study.