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

Abstract

The formation of acyclic azomethine imine 1,3-dipoles via an N,N′-prototropic shift of hydrazones in the presence of Lewis acids, Brønsted acids and hydrogen-bonding catalysts is a fundamental and powerful strategy...

Weak Nucleophiles in the Aza‐Michael Reaction

“…The first highly enantioselective Brønsted basecatalyzed aza-Michael addition of acylhydrazones to βtrifluoromethylated enones has been recently reported. [99] When β-CF 3 -enones (0.2 mmol) are treated with acylhydrazones (0.1 mmol) in the presence of 10 mol% urea-tertiary amine bifunctional catalyst, the target adducts are isolated in good to high yields (42-85%). The aza-Michael addition proceeds smoothly in toluene at 30 °C also on a gram-scale (up to ~2 g) and provides the same reaction products in high yields with 98% ee.…”

“…The first highly enantioselective Brønsted base‐catalyzed aza‐Michael addition of acylhydrazones to β‐trifluoromethylated enones has been recently reported [99] . When β‐CF 3 ‐enones (0.2 mmol) are treated with acylhydrazones (0.1 mmol) in the presence of 10 mol% urea‐tertiary amine bifunctional catalyst, the target adducts are isolated in good to high yields (42–85%).…”

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 .…”

“…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 . In this realm, the Jørgensen and the Chang groups pioneered bifunctional H-bond donor catalytic approaches involving Michael acceptors to synthesize pyrazolidines …”