Novel β ‐amino Amide Organocatalysts for the Synthesis of Pharmaceutically Relevant Oxindoles (original) (raw)
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Tetrahedron Letters, 2018
An enantioselective electrophilic amination of 3-substituted-2-oxindoles is reported, using bis(2,2,2-trichloroethyl)azo-dicarboxylate and commercially available Cinchona alkaloid organocatalysts. The best results were obtained in the reaction of 3-aryl substrates, with high to excellent yields (75% to quantitative) and good stereoselectivity (64-77% ee). Facile reductive conversion of the protected 3-hydrazino fragment into the corresponding primary amine was also demonstrated, to expand the synthetic flexibility of asymmetric electrophilic amination with azo-dicarboxylic esters en route to enantioenriched 3-amino-2-oxindoles. The absolute configuration of 3-amino-3-phenyl-2-oxindole was independently established by electronic circular dichroism (ECD), combined with time-dependent density functional theory (TDDFT). .
SYNTHETIC COMMUNICATIONS, 2017
Efficient zinc-mediated allylation, propargylation, and benzylation of isatin-derived imines were undertaken for the synthesis of 3-substituted 3-aminooxindoles with ≈80% yield. Such alternative approach has efficiently avoided the use of catalysts, severe reaction conditions, multistep procedures, and reaction additives. For exploring and materializing the synthetic utility, different allyl, propargyl, and benzyl bromides were used for generalizing the synthetic route. The structure of the synthesized compounds was established and confirmed by 1 H NMR, 13C NMR, FTIR, and mass spectroscopic techniques.
Facile and General Synthesis of Quaternary 3-Aminooxindoles
Organic Letters, 2008
A novel approach to the valuable quaternary 3-aminooxindole skeleton is reported on the basis of intramolecular arylation of enolates of substituted amino acids. The reaction tolerates dialkyl-and arylalkylamines as well as a range of carbon substituents (primary and secondary alkyl, aryl). The cyclization of N-indolyl-substituted substrates is accompanied by direct C-H arylation of the indole, leading to indolo-fused benzodiazepines.
Approach to 3-Aminoindolin-2-ones via Oxime Ether Functionalized Carbamoylcyclohexadienes
The Journal of Organic Chemistry, 2004
O-Benzyloxime ether substituted amidocyclohexadienes were prepared in three steps in good yields from 2-aminoacetophenone. EPR spectroscopic observations and product analyses showed that peroxide-induced decompositions of model compounds led to indolin-2-ones with benzyloxyaminyl substitution at their 3-positions. The cyclization steps were very rapid and took place regioselectively at the C-atoms of the CdN bonds, by 5-exo ring closures. An O-trityloxime ether analogue was also prepared. The cyclohexadienyl intermediate smoothly yielded an alkoxylaminyl radical again by rapid 5-exo-cyclization. However, ring closure was quickly followed by another -scission step that released the persistent trityl radical and a 3-nitrosoindolin-2-one derivative. EPR spectroscopic evidence showed that the nitroso compound trapped other transient intermediates to afford a series of nitroxides. GC-MS analyses of products formed in reactions including methyl thioglycolate indicated that 1-benzyl-3-methyl-1,3-dihydro-2H-indol-2-one was derived from the indolinone moiety.
Catalytic asymmetric synthesis of 3-hydroxyoxindole: a potentially bioactive molecule
RSC Advances, 2012
The recent emergence of biological activities of chiral 3-substituted-3-hydroxy-2-oxindoles has inspired synthetic chemists to develop new methodologies for their synthesis. Both chiral organocatalysts and organometallic catalysts have provided an important platform for their synthesis and in recent years, great achievements have been made in their catalytic asymmetric synthesis. This review summarizes the catalytic strategies for enantioselective synthesis of targeted frameworks.
Tetrahedron, 2011
The first (organo)catalytic method for regio-and chemoselective aza-FriedeleCrafts (FC) alkylation of indoles and pyrroles with commercially available methyl a-acetamidoacrylates has been discovered. It minimizes/eliminates common competing reactions that occur due to the high and multiatomnucleophilic character of indole and pyrrole. Diverse quaternary a-amino acids were successfully prepared in good yield and high selectivity using low catalyst loading. The enantioselective variant using BINOL-derived phosphoric acids was also explored with indole providing the desired FeC alkylation product with moderate enantioselectivities.
Asymmetric synthesis of 3,4-annulated indoles through an organocatalytic cascade approach
Chemical Communications, 2014
Therefore we tested the MacMillan's second generation type catalyst 4d using various polar and aprotic solvents (Table S1, entries 6-8), TFA as cocatalyst, at RT; the conversion increased dramatically, but besides the tricyclic target product 3k, the related N-alkylated compound 3k' was formed in not negligible amount and moreover, the enantiomeric excesses were unsatisfactory. No improvement was observed by replacing the cocatalyst: PTSA gave the N-alkylated 3k' as the predominantly product, while 2-nitro benzoic acid did not promote the reaction at all (Table S1, entries 9-10). By using DCM/i-PrOH mixture as solvent, as originally employed for the reaction between simple indoles and enals catalysed by 4d, 1 the enantioselectivity was improved to encouraging values, although the ratio between 3k and 3k' remained poor (Table S1, entry 12). We were unable to discriminate beetwen 3k and 3k', even by decreasing the amount of 2b (Table S1, entry 13). Thus, we switched to the N-Me indole derivative 1g as substrate. At RT, the reaction proceeded to complete conversion furnishing 3h as the only product with moderate enantioselectivity (Table S1, entry 14) which was improved by decreasing the temperature to-30 °C (Table S1, entry 15). A further decrease in the temperature did not increase the enantioselectivity (Table S1, entry 16).