Introduction of a New Stereocenter on C1-Functionalized 8-Oxabicyclo[3.2.1] oct-6-en 3-ones by a Regio- and Stereoselective Electrophilic Addition. Obtention of Polyfunctionalized Cycloheptanes with Five Stereocenters

A methodology to obtain polyfunctionalized cycloheptane synthons, with five stereocenters, is presented. The precursors are C1-functionalized 8-oxabicyclo[3.2.1]oct-6-en-3-ones, obtained by a [4+3] cycloaddition reaction. The stereoselective reduction of the carbonyl group on C3 of these cycloadducts, followed by an electrophilic addition of organic acids on the C6-C7 double bond, under controlled conditions, allows the introduction of a new stereocenters on C6. The introduction of this new substituent on C6 takes place in a regio- and stereoselective way by a preferential exo attack on the oxabicyclic substrates. This synthetic methodology is versatile enough to allow the preparation of a wide variety of polypropionate building blocks, with applications to the synthesis of natural products with biological interest.