NHC-catalysed retro-aldol/aldol cascade reaction enabling solvent-controlled stereodivergent synthesis of spirooxindoles

Expeditious entry into carbocyclic and heterocyclic spirooxindoles

“…Intermediate 194 further undergoes a retro aldol/aldol condensation reaction using N-heterocyclic carbene (NHC) C 28 as a catalyst in the presence of dichloroethane (DCE) affording exclusively the cis -isomer of spirocyclopentaneoxindole 195 and the corresponding trans -isomer- 195 in the presence of tetrahydrofuran (THF) as solvent (Scheme 114). 86 Hence four stereoisomers of 195 can be generated by different combinations of solvents (THF and DCE) and chiral secondary amine ( C 26 and ent - C 26 ). The reaction was executed in a sequential manner and the presence of secondary amine C 26 and acetic acid used in the formation of 112 does not affect the efficiency of NHC in the retro aldol reaction.…”

Enantioselective Construction of Spirooxindole-Fused Cyclopentanes

“…Reaction condition optimization, crystallographic data, description of computational methods, complete biological activity screening copies of 1 H NMR, 13 C NMR, and 19 F NMR, and copies of chiral HPLC (PDF) FAIR data, including the primary NMR FID files, for all compounds (ZIP)…”

“…C{ 1 H} NMR (101 MHz, chloroform-d): δ 201 3,. 178.3, 158.9 (d, J = 240.8 Hz, 1C), 138.1 (d, J = 2.0 Hz, 1C), 135.1, 134.8, 132.9 (d, J = 7.8 Hz, 1C), 128.7 (2C), 128.3 (2C), 128.2 (2C), 127.7, 127.4, 126.7 (2C), 114.3 (d, J = 23.2 Hz, 1C), 112.11 (d, J = 24.9 Hz, 1C), 109.8 (d, J = 8.2 Hz, 1C), 60.79 (d, J = 1.7 Hz, 1C), 56.5, 55.1, 43.9, 35.4,24.2 ppm 19. F NMR (376 MHz, chloroform-d): δ −120.51 (td, J = 8.7, 4.3 Hz) ppm.…”

“…19 F spectra were recorded with a Bruker AVANCE III 400 instrument. Chemical shifts for protons are given in δ relative to tetramethylsilane (TMS), and they are referenced to residual protium in the NMR solvent (chloroform-d: δ H = 7.26 ppm).…”

Dearomative tandem annulation to access chiral indoline-fused bicyclo[2.2.2]octanes using modularly designed organocatalysts

“…12 In continuation of our interest in organocatalysis and constructing biologically relevant frameworks, 13 we herein describe organocatalytic asymmetric dearomative tandem annulations of 3-nitroindoles and trans -7-oxo-5-heptenals (Scheme 1b). This work utilized an organocatalytic system 14 assembled by two chiral organocatalysts to promote the sequential Michael/Michael/aldol cascade. With this protocol, a broad range of chiral indoline-fused bicyclo[2.2.2]octanes featuring six vicinal stereogenic centers could be facilely accessed in a highly stereoselective manner.…”