Asymmetric Synthesis of Spiropyrazolones via Chiral Pd(0)/Ligand Complex-Catalyzed Formal [4+2] Cycloaddition of Vinyl Benzoxazinanones with Alkylidene Pyrazolones

Abstract

In the presence of the chiral Pd(0)/ligand complex, vinyl benzoxazinanones underwent the [4+2] cycloaddition with alkylidene pyrazolones smoothly and delivered spiropyrazolones in reasonable yields, diastereoselectivities, and eneantioselectivities (up to >99% yield, >99:1 dr and 99% ee). The absolute configuration of the obtained spiropyrazolones was unambiguously characterized with the use of X-ray single-crystal structure analysis. Moreover, the reaction mechanism was assumed to interpret the formation of the target compounds.

Recent Advances in Metal‐Catalyzed Decarboxylative Reactions of Vinyl Benzoxazinanones

“…Recently, Zhao and coworkers reported decarboxylative [4+2] cycloaddition of vinyl benzoxazinones with alkylidene pyrazolones catalyzed by Pd(PPh 3 ) 4 and chiral phosphoramidite L14 delivered spiropyrazolones ( 57 ) in reasonable yields, diastereoselectivities, and eneantioselectivities (Scheme 19). [22] Generally, substrates 1 bearing both an electron‐donating or ‐withdrawing R 1 group exhibited reasonable reactivities. And substrates 56 well endured the installation of both the electron‐rich and ‐poor aromatic ring as R 3 or R 4 groups.…”

Advances in Palladium‐Catalyzed Decarboxylative Cycloadditions of Cyclic Carbonates, Carbamates and Lactones

“…Notably, replacing the methyl group on nitrogen of 42 with H resulted in a failure for the reaction. In addition, asymmetric DCs of 108 with alkylidene pyrazolones 97 a were also achieved by the same group (Scheme 57, eq 2), furnishing a wide range of chiral spiropyrazolones 118 with good results under mild conditions [39b] . The N ‐H substituted vinyl benzoxazinanone failed to react with alkylidene pyrazolone under the standard conditions.…”

Recent advances in the applications of pyrazolone derivatives in enantioselective synthesis

“…Regarding spirocyclic pyrazolones, the Guo group and Zhao group utilized the zwitterionic intermediates 140 and 143 , respectively, as reactive species to support (4 + 2) cycloaddition with arylidene pyrazolinones 3aa (Scheme 30). 57 In Guo's work, in the presence of a complex of ( R )-DTBM-Segphos L11 and palladium, the key intermediates 140 were generated from 2-methylidenetrimethylene carbonates 138 , affording the tetrahydropyran-fused spirocyclic pyrazolones 139 in high yields with excellent enantioselectivities (Scheme 30a). 57 a In addition, with Pd(0)/ L12 as the catalyst, vinyl benzoxazinanones 141 were used by Zhao and co-workers to form the key intermediates 143 .…”