Copper-catalyzed C(sp3)-OH cleavage with concomitant C-C coupling: synthesis of 3-substituted isoindolinones.

Copper(II) trifluoromethanesulfonate (Cu(OTf)2) efficiently catalyzes the C-C coupling of 3-hydoxyisoindolinones with a variety of aryl-, heteroaryl-, and alkenylboronic acids to furnish C(3) aryl-, heteroaryl-, and alkenyl-substituted isoindolinones. The coupling reactions work smoothly in 1,2-dicholoroethane (DCE) reflux, to effect both inter- and intramolecular versions. This is the first report on C(sp(3))-OH cleavage with concomitant C-C coupling. The photolabile 2-nitrobenzyl protecting group is most appropriate for promotion of the coupling reaction and for deprotection. The tetracyclic ring motif of the alkaloid neuvamine was prepared by applying the newly developed copper-catalyzed C-C coupling.