Development and Application of New Spiroketalization and Allylic Transposition

The direct rhenium-catalyzed [1,3]-transposition of allylic alcohols and their silyl ethers is a powerful synthetic tool for the preparation of less accessible isomer from a more readily available precursor in a single operation. It is highly atom- and step-economical process because it allows for the structural reorganization within a molecule of interest without its prior derivatization. As a result, it holds a significant advantage over the closely related [1,3]-dioxa-Cope rearrangement of allylic esters eliminating the need of the formation and removal of the prerequisite ester moiety. Although this transformation has been known since late 1960s, the development of synthetically useful protocols that allow for a high level of regio- and stereoselectivity control and their synthetic applications have emerged only recently. The synthetic work described herein focuses on the development of regio- and stereoselective allylic [1,3]-transposition relying on the relief of ring strain. Through this process, eight-membered ring siloxadienes undergo a ring contraction to the corresponding six-membered siloxenes bearing an endocyclic double bond and an alkenyl substituent. The utility of ring-contractive allylic transposition is further discussed in the asymmetric total synthesis of (–)-amphidinolide V. Special emphasis is also given to the application of silicon-tethered ring-closing enyne and diene metathesis as well as direct proline-mediated cross-aldol condensation of aldehydes, which enabled a concise synthetic approach for the natural product. In addition, the asymmetric total synthesis of (–)-dactylolide is presented. It illustrates the application of the regio- and stereoselective [1,3]-transposition of silyl ethers bearing tethered boronate moiety for the preparation of a key (Z)-trisubstituted vinylboronate building block. Also, along the synthesis, the utility of a tandem ruthenium-catalyzed Alder-ene reaction followed by a palladium-catalyzed π-allyl etherification for stereoselective construction of a 2,6-disubstituted tetrahydropyran subunit has been demonstrated. Finally, an efficient one-step protocol relying on π-Lewis acid-catalyzed hydroalkoxylation–hydration is presented for the synthesis of 5-5-5, 5-5-6, and 6-5-6 bis-spiroketal structures of polyketide natural products. Additionally, the equilibration behavior of cis- and trans-bis-spiroketals and the factors that dictate the equilibrium ratio are discussed.