Palladium-Catalyzed Arylation of Hydantoins with Aryl Chlorides Enabled by Ylide-Functionalized Phosphines (YPhos)

Abstract

The hydantoin moiety is an important structural motif present in various pharmaceuticals. Palladium complexes bearing electron-rich, bulky ylide-functionalized phosphine (YPhos) ligands were found to catalyze the arylation of N-protected hydantoins with broadly available aryl chlorides. Selective monoarylations, sequential diarylations, and arylation-alkylation sequences have been achieved. In combination with stepwise deprotection strategies, this opens up an expedient access to a wide variety of hydantoins, including derivatives of the anticonvulsant drugs phenytoin and mephenytoin.

Chiral Quaternary Ammonium Salt‐Catalyzed Enantioselective Addition Reactions of Hydantoins

“…Considering the general value of (chiral) hydantoins, it comes as no surprise that the development of (asymmetric) reaction protocols to access (enantioenriched) hydantoins 1 or 2 emerged as an important task. [4,5.9–26] Besides valuable strategies to construct the heterocyclic motive itself, like the Biltz, [9,26] the Bucherer‐Bergs, [10] the Urech, [11] or the Read synthesis, [12] also classical α‐functionalizations of preformed non‐ or mono‐substituted hydantoins have been established to access structurally diverse α‐(di)substituted hydantoins ( Scheme 1 A ) [13–25] . Various types of C‐electrophiles have been successfully utilized to access hydantoins 2 .…”