Enantioselective formal [3+2]-cycloadditions to access spirooxindoles bearing four contiguous stereocenters through synergistic catalysis

Abstract

An enantioselective ring-opening formal [3+2]-cycloaddition of spirovinylcyclopropyl oxindoles with enals via synergistic catalysis of palladium(0) and chiral organocatalyst has been developed, affording spirooxindoles bearing four contiguous stereocenters in good yields...

Enantioselective Synthesis of Spirocyclopentane Oxindoles Bearing Five Consecutive Stereocenters through Secondary Amine‐Catalyzed [3+2] Cycloaddition

“…For example, under the treatment of Jones reagent in acetone, the reduction of the aldehyde moiety of compound 3 a generated carboxylic acid 4 in 86 % yield with 99 : 1 er. [15] Also, the Wittig reaction between 3 a and phosphorus ylide proceeded efficiently to afford the corresponding ester 5 in 95 % yield. [16] Moreover, treating 3 a with phosphorus tribromide in DCM at 0 °C could produce the corresponding product 6 in high yield (82 %) without losing enantiomeric purity (99 : 1 er).…”

“…With newly formed spirocyclopentaneoxindole 3 a in hand, subsequent transformations were conducted, which demonstrated the applicability of this method (Scheme 2b). For example, under the treatment of Jones reagent in acetone, the reduction of the aldehyde moiety of compound 3 a generated carboxylic acid 4 in 86 % yield with 99 : 1 er [15] . Also, the Wittig reaction between 3 a and phosphorus ylide proceeded efficiently to afford the corresponding ester 5 in 95 % yield [16] .…”

Palladium-Catalyzed Annulative Coupling of Spirovinylcyclopropyl Oxindoles with p-Quinone Methides

“…To understand the mechanistic pathways, ,, DFT calculations were carried out using 1a and 2a as the model substrates at 298 K in the gas phase (Figure ). First, the Pd-catalyzed ring opening of SVCP 1a can produce the Pd- stabilized zwitterionic π-allyl complex Int-I in an exergonic pathway (Δ G 298 = −7.1 kcal/mol). ,− ,, Si -face approach of 2a toward Int-I can lead the formation of Int-II via transition state TS-I with an energy barrier of 15.3 kcal/mol.…”

Ligand-Controlled Palladium-Catalyzed Asymmetric [4+3] and [2+3] Annulation Reactions of Spirovinylcyclopropyl Oxindoles with o-Quinone Methides

“…In addition, some functionalized benzo­[ b ]­oxepines show antifungal, antibiotic, and allelopathic activities, as well as other biological activities (Figure ). Because of the activities and potential synthetic utility of these types of compounds, they have been attracting growing interest from synthetic chemists …”

“…We commenced our investigation with 1′-methyl-2-vinyl-spiro­(cyclopropane-1,3′-indolin)-2′-one 1a and o -QM 2a as the model substrates in dichloromethane (DCM) containing Pd­(PPh 3 ) 4 (10 mol %) and various chiral ligands (10 mol %) at 25 °C (Table ). Phosphoramidite ligand L1 afforded an approximately 2:1 mixture of [4+3] annulation product 3a and [2+3] annulation product bispiro­[benzo­[ d ]­[1,3]­dioxole-cyclopentane-indoline]­dione 4a in 77% combined yield with fair enantioselectivity (Table , entry 1).…”