Copper-Mediated Vicarious Nucleophilic Substitution
Doktorsavhandling, 1993

This thesis suggests and examines a novel approach for copper-mediated cross-couplings. We call this mechanistic approach copper-mediated vicarious nucleophilic substitution. Our hypothesis is that copper-promoted cross-couplings proceed via an intermediate s-adduct, a Meisenheimer adduct. This hypothesis is valid for cross-couplings between 1,3-dinitrobenzene and halogenated carbanions in the presence of copper tert-butoxide and pyridine. The hypothesis is also shown to be valid for cross-couplings between 1,3-dinitrobenzene or 1,3,5-trinitrobenzene and electron-rich iodoarenes, which is exemplified by the productive cross-coupling between iodophenols and dinitro- or trinitrobenzene. The reaction is generally applicable to iodinated methylene compounds, such as iodomethyl phenyl sulfone, iodoacetic esters and iodoacetonitrile. The bromo analogues are less efficient if an extra electron-withdrawing group is not present, while bromomalonic esters couple in good yields. The mechanism for these couplings is similar to that of ordinary vicarious nucleophilic substitution. The copper-mediation give a very high selectivity for substitution at C-2 of the dinitroarene. This thesis also presents an extension of the Castro coupling. With 2-iodophenols and ethyl propiolate as starting materials this extension gives isocoumestans (tetracyclic compounds) in a one-pot synthesis rather than the expected 2-substituted benzofurans. Cupriated benzofurans are suggested to be intermediates in this reaction. The scope and limitations of this extension are examined.


Olof Haglund

Institutionen för organisk kemi





Doktorsavhandlingar vid Chalmers tekniska högskola. Ny serie: 948