New approaches in asymmetric synthesis of tetrahydrofuran and tetrahydropyran-derivatives with potential application in the preparation of bioactive molecules

Abstract

The incredible number of bioactive natural products containing tetrahydrofuran (THF) and tetrahydropyran derivatives (THP) have been driven the development of new methods of preparing functionalized cyclic ethers. This research project will focus on the development and application of new synthetic methodologies involving the preparation of substituted cyclic ethers for the synthesis of natural products and bioactive molecules. One of the research topics deals with cobalt-catalyzed asymmetric cascade aerobic oxidative-cyclization/ radical-cyclization reactions. This reaction employs a low cost metal catalyst, showing low toxicity, broad access, performed in PA grade solvents in an open system using molecular oxygen as the oxidant, and with high tolerance to functional groups. This reaction generates a radical, allowing further functionalization through cascade reactions that will add structural complexity in just one step. An intramolecular versions will be investigated and will provide highly functionalized-tetrahydrofuran derivatives. In addition, we aim to provide further evidences on the nature of this transformation by theoretical calculations. In other shaft work, we intend to develop a new synthetic methodology allowing quick access to trisubstituted-THP, with special attention to 2,6-cis and 2,6-trans relations, employing epoxy-diols via one pot and cascade reactions. To this end, studies on the asymmetric synthesis of epoxy-diols from aldol adducts obtained by 1,5-diastereoselective aldol reactions will be performed. (AU)