Organocatalytic Enantioselective Alkylation of Pyrazol‐3‐ones with Isatin‐Derived Ketimines: Stereocontrolled Construction of Vicinal Tetrasubstituted Stereocenters

Abstract

Aq uinine-derived thiourea catalysed the enantioselective addition of 4-substituted pyrazolones to isatin-derived ketimines, providing avariety of aminooxindole-pyrazolonea dducts containing congested vicinal tetrasubstituted stereocentres with excellent outcomes (up to 98% yield, > 20:1 dr and 98% ee).

Tunable Aerobic Oxidative Hydroxylation/Dehydrogenative Homocoupling of Pyrazol-5-ones under Transition-Metal-Free Conditions

“…Pyrazol-5-one skeletons represent privileged structural units ubiquitously appearing in biologically active natural products and synthetic drugs, such as the first synthetic antipyretic and analgesic drug by Ludwig Knorr in 1883, , antibacterial agents, and p38 inhibitors . Concerning extensive applications of multifunctionalized pyrazol-5-ones , and our sustaining interest in the aerobic oxidative reactions, we determined to devote our efforts on the exploration for efficient derivatization of pyrazoles by an aerobic oxidative strategy. Recently, Wang and co-workers reported an oxidative hydroxylation at the C4-position of pyrazol-5-ones with cumene hydroperoxide (CHP) as the oxidant (Scheme a) .…”

Chiral Bifunctional Ferrocenylphosphine‐Catalyzed Enantioselective Allylic Alkylation of Morita−Baylis−Hillman Carbonates with Pyrazolin‐5‐ones

“…In addition, similar results were obtained when using sterically hindered tertiary phosphine catalysts LB7 and LB8 (Table 1, entries 7 and 8). Moreover, the influence of solvent was also evaluated, solvents such as mesitylene, trifluoromethylbenzene, DCM, CH 3 CN and THF were failed to give better yield than toluene (Table 1, entries [10][11][12][13][14]. Moreover, the influence of solvent was also evaluated, solvents such as mesitylene, trifluoromethylbenzene, DCM, CH 3 CN and THF were failed to give better yield than toluene (Table 1, entries [10][11][12][13][14].…”

“…To date, the chiral tertiary-amine catalyzed asymmetric transformations using pyrazolin-5-ones as nucleophilic reaction partners were well established (Scheme 1a). [12] Very recently, Liu and co-workers, described bifunctional thiourea catalyzed enantioselective 1,6-addition between pyrazol-5-ones and 3methyl-4-nitro-5 alkenylisoxazoles, providing the corresponding acetylated pyrazoles after in situ treatment with AcCl/Et 3 N. [13] Beside chiral tertiary-amine, organometallic catalysis was also enable to promote these reactions. [12] Very recently, Liu and co-workers, described bifunctional thiourea catalyzed enantioselective 1,6-addition between pyrazol-5-ones and 3methyl-4-nitro-5 alkenylisoxazoles, providing the corresponding acetylated pyrazoles after in situ treatment with AcCl/Et 3 N. [13] Beside chiral tertiary-amine, organometallic catalysis was also enable to promote these reactions.…”

Organocatalytic Enantioselective Synthesis of Chiral Spiro‐indoline‐pyrazolones through a formal [4+1] Annulation Reaction of 4‐Bromopyrazolones and aza‐ortho‐Quinone Methides

“…[27] Therefore, the development of efficient strategies for the construction of spiro-indoline and spiro-pyrazolone derivatives in a selective way is highly valuable for medicinal chemistry and it is worth it for organic synthesis. Therefore, as a part of our ongoing interest in organocatalytic stereoselective synthesis of pyrazolones bearing a quaternary stereocenter [30][31][32] and chiral spirocyclic compounds [33,34] we became interested in the study of the synthesis of spirocyclic compounds bearing a pyrazolone and an indoline scaffolds (Scheme 1C).…”