Preparation of new polyfunctional magnesiated heterocycles using a chlorine-, bromine-, or iodine-magnesium exchange

The reaction of heteroaryl iodides with i-PrMgBr (ca. 1.0 equiv) in THF pro vides the corresponding magnesiated heterocycles. Functional groups such as an ester, cyano, or chloride functions are tolerated in these new Grignard reagents if the exchange can be performed below -20 degrees C. This is the case for all heterocycles bearing electron-withdrawing groups or chelating functions facilitating the iodine-magnesium exchange. In many cases, the e xchange can be extended to heteroaryl bromides, and a case of a chlorine-ma gnesium exchange is described with tetrachlorothiophene. This new preparati on of functionalized heteroarylmagnesium compounds provides after reaction with various electrophiles a new entry to a broad range of polyfunctional p yridines, imidazoles, furanes, thiophenes, pyrroles, antipyrines, and uraci l derivatives. The application of the halogen-magnesium exchange in the sol id phase allows the performance of solid-phase synthesis, with potential ap plications for combinatorial chemistry.