Copper(i)-catalyzed asymmetric [3 + 2] cycloaddition of N-ester acylhydrazones and β-trifluoromethyl-α,β-unsaturated ketones

Abstract

Herein, the first copper(I)-catalyzed asymmetric 1,3-dipolar [3+2] cycloaddition of N-ester acylhydrazones and β-trifluoromethyl-α,β-unsaturated ketones has been developed, affording an array of chiral pyrazolidine derivatives containing a trifluoromethyl moiety bearing vicinal...

β-Trifluoromethylated enones as trifluoromethylated synthons in asymmetric catalysis

“…In 2022, Chang and Zhu's group reported a highly enantioselective formal asymmetric [3 + 2] cycloaddition of N -ester acylhydrazones to β-trifluoromethyl-α,β-unsaturated ketones, in the presence of chiral CuI/ferrocene-based hybrid chiral P,N complex L7 , providing a facile route to chiral pyrazolidine derivatives containing a trifluoromethyl moiety bearing three vicinal stereocenters in good to excellent yields with effective control of both diastereoselectivity and enantioselectivity. 50 In addition, the chiral pyrazolidine compounds showcased potential antitumor activity (Scheme 31).…”

Asymmetric Brønsted base-catalyzed aza-Michael addition and [3 + 2] cycloaddition reactions of N-ester acylhydrazones and enones

“…Hydrazone derivatives are very important and valuable compounds due to their biological properties and widespread application in medicinal chemistry and materials science, 1 and developing efficient transformation strategies for hydrazones to access more value-added compounds has attracted the attention of organic chemists. 2 Over the past few decades, various elegant asymmetric 1,3-dipolar [3 + 2] cycloaddition protocols have been established to synthesize chiral pyrazolidines from hydrazones and olefins using Lewis acids, 3 Brønsted acids 4 and hydrogen bonding 5 catalysts, respectively. Under thermal or strongly acidic conditions, the azomethine imine tautomer is suggested to be formed from the corresponding N -keto acyl hydrazone by an N , N ′-prototropic shift.…”

Umpolung Reactivity of in Situ Derived Aryl Hydrazones: An Asymmetric Brønsted Acid Catalyzed Strategy to Access Fused Pyrazolidines

“…Unlike the asymmetric synthesis of acyclic diazaenes and 6-membered diaza-heterocycles, there is still a dearth of comprehensive reports detailing the umpolung reactivity of hydrazones in the organocatalytic asymmetric synthesis of 5-membered diaza-heterocycles. Upon delving into relevant literature on such methodology, we found limited studies on synthesizing enantiomerically enriched pyrazolidines (Scheme B-a). − In 2012, the Rueping and Tsogoeva groups separately exploited the conventional electrophilic behavior of hydrazones by introducing electron-deficient groups onto the hydrazine component in Brønsted acid-catalyzed (3 + 2) cycloaddition reactions with alkenes . Additionally, the Vicario group employed a similar catalytic system for their transannular and desymmetrization reactions, aiming to synthesize optically active 5-membered bicyclic and fused diaza-heterocycles .…”