Toward the Generation of 2-Amino-3-Formyl Difunctionalized Chromones via Pd-Enabled Rearrangement Strategy

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(sp2)–O bond and one C(sp2)–C(sp2) 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.

Dearomative spiroannulation of indoles enabled by the diaza-[1,2]-Wittig rearrangement

“…Skeletal rearrangement enables rapid molecular editing to synthesize sophisticated products, making it a powerful method for organic synthesis. [39][40][41][42][43][44][45] The [1,2]-Wittig rearrange-ment is a classic example, where ethers take part in a rearrangement to give their corresponding alcohols via O-to-C [1,2]-alkyl migration (Scheme 2A). 46,47 However, harsh reaction conditions and many competing pathways limit its synthetic utility.…”

Controllable Synthesis of N-Heterocycles via Hydride Transfer Strategy-Enabled Formal [5 + 1] and [5 + 2] Cyclizations

“…Based on the above experiments and previous reports, a plausible mechanism was proposed to rationalize the selective [5 + 1] and [5 + 2] cyclizations (Scheme ). At the outset, the carbonyl group of 2 was activated by Brønsted acid through the Friedel–Crafts reaction and dehydration process to generate the intermediate I .…”

Iodomethane in C1 chemistry: application in palladium-catalyzed [2 + 2 + 1] annulation

“…4 As such, exploration of a new strategy toward the syntheses of chromone derivatives is highly desirable. 5…”