Iridium-Catalyzed Intramolecular Asymmetric Allylation of Vinyl Benzoxazinones for the Synthesis of Chiral 4H-3,1-Benzoxazines via Kinetic Resolution

Abstract

Chiral benzoxazinones and 4H-3,1-benzoxazines as important motifs are widely found in abundant pharmaceuticals and biological molecules. We herein successfully developed the first kinetic resolution (KR) process of racemic benzoxazinones through Ir-catalyzed asymmetric intramolecular allylation, furnishing a wide range of chiral benzoxazinones and 4H-3,1-benzoxazines with excellent results via outstanding KR performances (with the s factor up to 170). This protocol exhibited broad substrate scope generality and good functional group tolerance, and the chiral 4H-3,1-benzoxazine products could be readily transformed to other useful optically active heterocycles.

Advancements in Asymmetric Catalytic Approaches Involving Benzoxazinone Derivatives

“…In 2023, He, Gu and Dong reported the first kinetic resolution process of racemic benzoxazinones 1 through Ir-catalyzed asymmetric intramolecular allylation, [43] affording a series of chiral benzoxazinones (R)-1 and 4H-3,1-benzoxazines 74 with excellent results [(R)-1: up to 49% yield, 99% ee; 74: up to 49% yield, 96% ee] via kinetic resolution performances (s factor up to 170). To account for the observed stereochemical outcome, a plausible catalytic cycle was suggested (Scheme 26), which revealed that the difference of activity between Ir(I)/1 complex was crucial, and the higher reactive Ir(I)/(S)-1 complex went through decarboxylative oxidation addition and could result in the preferential generation of zwitterionic Ir-π-allyl species through the kinetic resolution process, and thus (R)-1 was recovered.…”

Recent advances in intramolecular kinetic resolution reactions

“…Very recently, the Dong group developed the first kinetic resolution of racemic benzoxazinones through an Ir-catalyzed asymmetric intramolecular allylation reaction, obtaining a series of chiral benzoxazinones and 4 H -3,1-benzoxazines with excellent enantioselectivities (Scheme 15). 24 A wide range of substrates were tolerated, including electron-donating groups or electron-withdrawing groups on the aromatic moiety of benzamides. As the proposed catalytic cycle illustrated, the coordination of [Ir( i )*] to L-2 will distinguish [Ir( i )*]/( S )- 33 and [Ir( i )*]/( R )- 33 complexes at first, and then the [Ir( i )*]/( S )- 33 complex undergoes decarboxylative oxidation addition due to their preponderant coordination.…”