Metal-Catalyzed Cyclization of β- and γ-Allenols Derived from D-Glyceraldehyde-Synthesis of Enantiopure Dihydropyrans and Tetrahydrooxepines: An Experimental and Theoretical Study

Regiocontrolled metal-catalyzed preparations of enantiopure dihydropyrans and tetrahydrooxepines have been synthesized starting from beta- and gamma-allenols derived from D-glyceraldehyde. The Pd-II-catalyzed cyclizative coupling reactions of beta-allenols 1a and 1b with allyl bromide effectively afforded enantiopure tetrafunctionalized dihydropyrans through a 6-endo oxy-cyclization protocol, whereas the gold-, platinum-, and palladium-mediated heterocyclization of gamma-allenol 2 furnished tetrahydrooxepines 13-16 through regioselective 7-endo-trig oxy-cyclization reactions. Moreover, density functional calculations were performed to predict the regioselectivity of the gamma-allenol cycloetherification to tetrahydrooxepines oil the basis of both the tether nature and characteristics of the metals, and to gain an insight into the mechanism of the oxycyclization reactions.