Accessing Medicinally Relevant O‐Benzofused Heterocycles through C−X Activation: Recent Trends

Abstract

In this Review, we address the recent advances in the elaboration of medicinally relevant oxygen benzofused heterocycles by palladium and copper catalyzed CÀ X activation of halo arene precursors. This attractive transformation has shown remarkable versatility and efficiency as a synthetic toolkit leading to the construction of numerous scaffolds with high structural diversity in an atom-economical manner. We covered recent examples that considered the application of this strategy using miscellaneous coupling partners and conditions. The haloarene motif has proven to be an exceptional candidate principally due to its availability and cost, and in this review, we showcase relevant and appropriate examples of its use in catalytic reactions leading to medicinally important targets.

Sonogashira Cross-Coupling of Aryl Ammonium Salts by Selective C–N Activation Catalyzed by Air- and Moisture-Stable, Highly Active [Pd(NHC)(3-CF3-An)Cl2] (An = Aniline) Precatalysts

“…Activation of N–C bonds has recently emerged as an attractive approach in transition metal catalysis . In this context, over the years, a plethora of electrophilic coupling partners have been developed, predominantly focused on halides and phenolic electrophiles, , while more recent studies have begun to address the cross-coupling of aryl sulfur and aryl phosphorus bonds. , With respect to aromatic carbon–nitrogen bonds, this mode of oxidative addition is severely underdeveloped despite the prominent role of aromatic carbon–nitrogen bonds in organic synthesis and drug discovery . Out of several classes of C–N electrophiles, including the recent surge of interest in amide bond C–N activation, the use of trialkyl ammonium salts as readily available, safe, and benign C–N electrophiles is highly desirable. , Following the pioneering studies by Wenkert and MacMillan on Ni-catalyzed Kumada and Suzuki cross-coupling of aryltrimethylammonium salts, recent advances have been made by using specifically designed ligands and substrate classes for activation of C–N bonds in aryl ammonium salts. , …”