Diastereoselective Construction of Densely Functionalized 1-Halocyclopentenes Using an Alkynyl Halo-Prins/Halo-Nazarov Cyclization Strategy.

A diastereoselective two-step strategy for the synthesis of densely functionalized 1-halocyclopentenes with several chiral centers has been developed. In the first step, a multicomponent alkynyl halo-Prins reaction joins an enyne, a carbonyl derivative, and either a chloride, bromide, or iodide to produce a cyclic ether intermediate. In the subsequent step, the intermediate is ionized to generate a halopentadienyl cation, which undergoes an interrupted halo-Nazarov cyclization. The products contain three new contiguous stereogenic centers, generated with a high level of stereocontrol, as well as a vinyl halide allowing for additional functionalization. The strategy creates two new carbon-carbon bonds, one carbon-halide bond, and one carbon-oxygen bond.