Highly Enantio- and Diastereoselective Generation of Two Quaternary Centers in Spirocyclopropanation of Oxindole Derivatives (original) (raw)
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ChemInform, 2015
Asymmetric Diastereoselective Synthesis of Spirocyclopropane Derivatives of Oxindole.-The title reaction is based on the Michael addition of 3-chlorooxindole (I) to unsaturated 1,4-dicarbonyl compounds (II) and (IV), followed by an intramolecular nucleophilic substitution. trans-Spirocyclopropane oxindole derivatives (III) and (V) are formed in high diastereo-and enantioselectivity.-(OSEKA, M.; NOOLE,
Angewandte Chemie International Edition, 2009
The structural complexity and well-defined three-dimensional architecture of natural molecules are generally correlated with specificity of action and potentially useful biological properties. This complexity has inspired generations of synthetic chemists to design novel enantioselective strategies for assembling challenging target structures and reproducing the rich structural diversity inherent in natural molecules. This symbiotic correlation between natural compounds synthesis and the discovery of effective asymmetric-generally catalytic -technologies lies at the heart of the synthetic chemistry innovation. Despite the substantial advances made thus far, the construction of highly strained polycyclic structures (particularly those that contain spiro-stereocenters) and the generation of all-carbon quaternary stereocenters still remain daunting targets for synthesis. The spirocyclic oxindole core is featured in a number of natural products [6] as well as medicinally relevant compounds [7] ), but its stereocontrolled synthesis, particularly installing the challenging spiro-quaternary stereocenter, poses a great synthetic problem. Only a few venerable asymmetric transformations, such as cycloaddition processes [8] or the intramolecular Heck reaction, [9] have proven suitable for achieving this challenging goal.
Journal of Organic Chemistry, 2023
The present study reports an asymmetric organocascade reaction of oxindole-derived alkenes with 3-bromo-1nitropropane efficiently catalyzed by the bifunctional catalyst. Spirooxindole-fused cyclopentanes were produced in moderate-togood isolated yields (15-69%) with excellent stereochemical outcomes. The synthetic utility of the protocol was exemplified on a set of additional transformations of the corresponding spirooxidondole compounds. 1 C1 K2CO3 24 17/1 58 99 2 C2 K2CO3 24 3/1 39 92 3 C3 K2CO3 24 3/1 58 91 4 C1 Na2CO3 48 20/1 55 99 5 C1 NaHCO3 168 20/1 32 99 6 C1 DIPEA 24 2/1 49 98 7 e C1 K2CO3 2 3/1 38 91 8 f C1 K2CO3 3 8/1 23 99 9 g C1 K2CO3 24 >20/1 59 99 10 h C1 K2CO3 18 >20/1 57 99 11 i C1 K2CO3 45 >20/1 64 99 a Reactions were conducted with 1a (0.1 mmol), 2a (0.2 mmol), corresponding base (0.2 mmol), and catalyst (20 mol%) in DCM (1.0 ml) at room temperature. b Determined by 1 H-NMR of the crude reaction mixture (3a/4a). c Isolated yield of 3a after column chromatography. d Determined by chiral HPLC analysis. e EtOAc was used. f MTBE was used. g CHCl3 was used. h Reaction was conducted with 1a (0.10 mmol), 3a (0.15 mmol), C1 (20 mol%) in CHCl3 (1.0 ml) at room temperature. i Reaction was conducted with 1a (0.10 mmol), 3a (0.15 mmol), C1 (1 mol%) in CHCl3 (1.0 ml) at room temperature.
ACS Catalysis, 2015
The highly enantioselective (up to >99.5:0.5 er) synthesis of polysubstituted spirocyclic oxindoles with four new contiguous stereocenters, including the spiro all-carbon quaternary center, is disclosed. It is accomplished by the highly stereoselective control of a dynamic conjugate/intramolecular allylic alkylation relay sequence based on the synergistic cooperation of metal and chiral amine catalysts in which the careful selection of organic ligand, metal complex, and chiral amine is essential. The intramolecular C−C bond-forming step occurred only when both the metal and chiral amine catalysts were present.
The spirooxindole moiety is one of the most important structural frameworks and is frequently found in many natural products [1a-i] and clinical pharmaceuticals. [1d,j-l] Therefore, the development of simple synthetic strategies for obtaining spirooxindole derivatives has been and continues to be an attractive area in synthetic and medicinal chemistry. [1f-i, 2a-f] As part of our ongoing research into the Baylis-Hillman (BH) reaction, herein, we report the interesting sterically directed cycloaddition reactions of the dipoles that are generated from Baylis-Hillman bromides with isatins as dipolarophiles, thus providing a facile strategy for the synthesis of spiroepoxy oxindoles and spirodihydrofuran oxindoles in a one-pot operation.
Synthesis of Cyclopropane Spirooxindoles by means of a Vinylogous Organocatalytic Cascade
Asian Journal of Organic Chemistry, 2014
The 1 H and 13 C NMR spectra were recorded at 300 MHz, 400 MHz or 500 MHz for 1 H or at 75 MHz, 100 MHz and 125 MHz for 13 C, respectively. The chemical shifts (δ) for 1 H and 13 C are given in ppm relative to residual signals of the solvents (CHCl 3 : δ 7.26 ppm 1 H NMR, 77.16 ppm 13 C NMR; DMSO (d 6): δ 2.50 ppm 1 H NMR, 39.52 ppm 13 C NMR). Coupling constants are given in Hz. When necessary, 1 H and 13 C signals were assigned by means g-HSQC and g-HMBC 2D-NMR sequences. The following abbreviations are used to indicate the multiplicity: