Stereoselective Heck arylation of a functionalized cyclopentenyl ether using ( S)- N-methyl-pyrrolidine as the stereochemical controller

Abstract

The study of a series of palladium(0)-catalyzed C2-arylations of a 1-cyclopentenyl ether equipped with a chiral ( S)- N-methyl-pyrrolidine auxiliary is reported. Stereoselective Heck monoarylations were performed using aryl iodides under classical heating conditions for 1.7–3.0 h at 80 °C and in one case using 30 min of microwave irradiation at 110 °C. To further explore the scope and nature of this stereoselective methodology, aryl bromides were also utilized as arylating agents, using 20 min of microwave processing at 120–130 °C. High to excellent diastereopurities (90–98% de) were obtained according to 1H NMR and GC–MS analyses. The prolinol fragment apparently controlled the diastereoselectivity of the Heck reaction by presenting the arylpalladium species from the preferred side of the double bond. By X-ray structure diffraction analysis of an N-quaternized Heck product, the absolute configuration of the new stereocenter was established as ( R), supporting a Si-face migratory insertion.