Reports: GB1
43210-GB1 Regioselective Synthesis of Functionalized Furanones and Dihydropyranones by Olefin Metathesis
Oxygenated heterocycles are common structural components of chemically and biologically significant natural products. We have developed concise syntheses of two types of O-heterocycles employing tandem olefin metathesis as key steps. Our initial study focused on the preparation of allyl 5H-furan-2-ones by size-selective ring-closing metathesis (RCM) of substituted 1,5-hexadien-3-yl acrylates and examined in situ cross metathesis (CM) of RCM products as an efficient and flexible method for the construction of highly functionalized furanones. We examined the scope of the reaction and optimized reaction parameters in the context of a convergent synthesis of squamostolide, a bioactive member of the Annonaceous acetogenin family of natural products. This was followed by an extension of our studies on tandem metathesis to the ring-opening(ROM)/RCM(ring-rearrangement)/CM of the vinyl ether of endo-7-oxanorbornen-2-ol for the synthesis of stereodefined 2,6-dioxabicyclo[3.3.0]octene derivatives. The efficiency and flexibility of this approach as well as the high degree of functionality present in the products of this ring-rearrangement/CM cascade make it well suited for application in total synthesis. This research has provided a training ground for promising scientists and has been published in Tetrahedron and Tetrahedron Letters.
