Prins-Type Cyclization Reactions in Natural Product Synthesis

Prins‐type cyclization reactions proceed through the intramolecular addition of a π‐nucleophile to an oxocarbenium ion or related species to generate a ring through carbon–carbon bond formation, often with excellent and predictable stereocontrol. The widespread presence of naturally occurring oxygen‐containing heterocycles has made these reactions exceedingly valuable for total synthesis efforts. This microreview covers several common variations of Prins‐type cyclizations and highlights their applicability to the total synthesis of natural products and analogs. Tetrahydropyrans are subunits in a wide range of biologically active natural products. Prins‐type cyclization reactions, in which a π‐nucleophile adds to an appended oxocarbenium ion, are effective for constructing these rings. This microreview covers variations of this reaction that have been applied to natural product synthesis with a focus on the method of oxocarbenium ion formation and type of π‐nucleophile.