Organocatalytic Asymmetric Cyclopropanation of 3-Acylcoumarins with 3-Halooxindoles: Access to Spirooxindole-cyclopropa[c]coumarin Compounds

Abstract

A highly diastereo- and enantioselective cyclopropanation reaction of 3-acylcoumarins with 3-halooxindoles catalyzed by an organocatalyst through a [2 + 1] Michael/intramolecular cyclization process was developed. This scenario provides a facile strategy to access spirooxindole-cyclopropa­[c]­coumarin compounds bearing three continuous stereocenters, including two vicinal quaternary all-carbon stereocenters with high to excellent diastereo- and enantioselectivities. The HRMS study revealed the vital importance of the ammonium ylide intermediate in the catalytic process.

Regiodivergent Organocatalytic Reactions

“…Chiral squaramide has been shown to successfully catalyze several reactions including Michael additions, and the Mannich, aza-Henry, and Strecker reactions. Moreover, these catalysts have successfully produced enantio-enriched products in single and domino/cascade reactions in various asymmetric organic transformations [168][169][170][171][172][173][174][175][176].…”

Asymmetric organocatalyzed synthesis of coumarin derivatives

“…More recently, Yuan et al developed a methodology for the synthesis of spiroonxindole-cyclopropa[ c ]coumarins 75 through the cyclopropanation of 3-acylcoumarins 43 and 3-halooxindoles 74 [ 58 ]. The authors chose a quinine-derived squaramide catalyst 73 to perform the [2 + 1] cycloaddition.…”

A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

“…3-Monohalooxindole heterocycles are not only present as a characteristic structural motif in numerous biological and medicinal molecules [1,2] but also possess dual nucleophilic and electrophilic character at the C-3 position. Owing to the dual nature at the C-3 position, 3-monohalooxindoles have emerged as a class of versatile building blocks for the construction of various 3,3-disubstituted oxindole and spirooxindole derivatives, such as spirocyclopropaneoxindoles [3][4][5][6][7][8][9][10][11], 3-β-aminosubstituted 3-halooxindoles [12][13][14], five-membered-ring-based spirooxindoles [15][16][17][18] and 3-alkyl-substituted 3-fluorooxin-doles (Figure 1) [19]. Despite the importance of 3-monohalooxindoles in organic synthesis and medicinal chemistry, only a few methods for the synthesis of these 3-monohalooxindoles have been reported.…”