N-Acyl-5,5-dimethylhydantoin, a New Mild Acyl-Transfer Reagent in Pd Catalysis: Highly Efficient Synthesis of Functionalized Ketones

Abstract

The palladium-catalyzed Suzuki−Miyaura cross-coupling of N-acyl-5,5-dimethylhydantoins with arylboronic acids has been developed via selective amides C−N bond cleavage. The new reagent is commercially available and air-/ moisture-stable, and it offers a variety of ketones in good yields through Suzuki coupling under mild conditions (up to 95%).

Recent Advances in Acyl Suzuki Cross-Coupling

“…This reaction gave moderate to good yields in a short reaction time. More recently, they used structurally-related N-acyl-5,5-dimethylhydantoins in the acyl Suzuki cross-coupling with aryl boronic acids (Scheme 26B) [95]. The use of commercially-available, air-and moisture-stable (IPr)Pd(allyl)Cl precatalyst as well as good tolerance to several functional groups are important features of this protocol.…”

Water Phase, Room Temperature, Ligand‐Free Suzuki–Miyaura Cross‐Coupling: A Green Gateway to Aryl Ketones by C–N Bond Cleavage

“…In 2017, Szostak and our groups both reported Pd‐catalyzed Suzuki–Miyaura coupling acylation of N ‐acylsuccinimides,[5b], [6h] respectively. As an acyl‐source, N ‐acylsuccinimides have several advantages: (a) N ‐acylsuccinimides can be efficiently synthesized from succinimides that are virtually nontoxic and widely available commodity chemical; (b) N ‐acylsuccinimides are crystalline, benign and shelf‐stable reagents, which demonstrate high atom utilization and efficient functional group transfer reagents in acylation reactions.…”

“…1‐[4‐(Trifluoromethyl)benzoyl]pyrrolidine‐2,5‐dione (1f): [5b] Following general procedure. 1f was purified by recrystallization to afford a white solid (0.94 g, 69.3 %).…”

“…Aryl ketones are commonly utilized in the synthesis of pharmaceuticals and functional materials, Over the past decades, palladium‐catalyzed Suzuki–Miyaura coupling reaction of electrophiles, including aryl halides, esters and amides with organoboron nucleophiles for synthesizing a series of aryl ketones has been developed. It has become one of the most powerful and important synthetic methods to construct aryl ketones via selective C–N bond transformations of activated amides.…”

“…[6x], [6g], However, in consideration of limited reactant solubility or lessen stability of catalysts in water, an efficient Suzuki–Miyaura coupling for synthesis of aryl ketones in aqueous media without any ligands or additive is rarely reported. With continued interest in the development of activated amide chemical conversion, it is valuable for us to develop a simple and environmentally friendly method for synthesis of aryl ketones from amides. Herein, we firstly utilize the high reactivity N ‐acylsuccinimides and potassium aryltrifluoroborates to develop water phase/room temperature/ligand‐free Suzuki–Miyaura coupling by C–N bonds cleavage (Scheme C).…”