Toward the Generation of 2-Amino-3-Formyl Difunctionalized Chromones via Pd-Enabled Rearrangement Strategy
Qi Tong, Ren-Feng Xiu, Jiahe Chen, Yun Zhang, Bao‐Dong Cui, Nan‐Wei Wan, Yong‐Zheng Chen, Wen‐Yong Han
Abstract
Accomplished herein is a rearrangement strategy for the highly efficient assembly of synthetically cumbersome while medicinally significant 2-amino-3-formyl chromones via palladium-catalyzed ring-opening, rearrangement, and cyclization process. Such a sequence enables the formation of one C(sp 2 )–O bond and one C(sp 2 )–C(sp 2 ) bond, and reconstruction of the benzo-γ-pyrone moiety in a single operation, thus producing the difunctionalized chromone-incorporated derivatives. The reaction proceeds in a shorter reaction time (30 min for 3-iodochromones in most cases) in a highly atom- and step-economical manner. The synthetic application of the current protocol is further demonstrated by late-stage modification of pharmaceuticals and their intermediates, gram-scale reactions, transformations of functional groups, as well as the synthesis of bioactive molecules and drugs. Mechanistic studies indicate that a nucleophilic ring-opening process of the benzo-γ-pyrone moiety, phenoxy anion intermediate, and an intramolecular palladium-catalyzed cyclization process might be involved in the present reaction system.