Intramolecular Prins cyclisations for the stereoselective synthesis of bicyclic tetrahydropyrans

摘要

Methyl (4E,7R)-7-hydroxyoctanoate was prepared in 71% yield from ethyl (R)-3-hydroxybutanoate and on reaction with a series of aldehydes in the presence of TMSOTf gave bicyclic oxygen heterocycles in good yields and with the creation of three new stereogenic centres in a single pot. Saturated oxygen containing heterocycles, of varying size, are common structural features of many biologically active natural products, for example the phorboxazoles and bryostatins; often these compounds are isolated in only minute quantities. In order to confirm their structures and gain sufficient material for full biological assessment of the natural products and analogues, the development of efficient methods for the synthesis of oxygen heterocycles remains an important goal.