Stereochemical evaluation of bis(phosphine) copper catalysts for the asymmetric alkylation of 3-bromooxindoles with α-arylated malonate esters

Lee, Chung Whan; Han, Seo‐Jung; Virgil, Scott C.; Stoltz, Brian M.

doi:10.1016/j.tet.2014.10.065

Cited by 12 publications

(8 citation statements)

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“…The utility of methods for indole synthesis could be broadened by considering them not only as synthetic targets, but as intermediates toward other heterocycles as well. Furthermore, mild and selective transformations of indoles may be applied to tryptophan fragments in applications such as bioconjugation. , As part of our research on new indole-related methodologies and on indole-containing natural products, we have discovered a mechanistically different sequence for oxidative fragmentation of indole and oxindole derivatives that is complementary to the prevailing synthetic and enzymatic pathways (Scheme C). This method facilitates C2–C3 bond cleavage of the oxindole ring with concomitant reaction with a nucleophile, thereby offering access to diverse heterocycles and aniline derivatives, which are unattainable by conventional biomimetic oxidations.…”

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confidence: 89%

Oxidative Fragmentations and Skeletal Rearrangements of Oxindole Derivatives

et al. 2017

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According to a procedure reported by Savige and Fontana, 2 the indole is dissolved in dimethyl sulfoxide (10 equiv) and concentrated hydrochloric acid (12 N, 18 equiv) is added dropwise at ambient temperature. Reaction progress is monitored by LCMS and is typically complete in less than 30 minutes. The reaction mixture is neutralized (pH > 6) with concentrated ammonium hydroxide and extracted with dichloromethane. The combined organic phases are dried over sodium sulfate, filtered, and concentrated. The residue is purified by column chromatography to afford the oxindole product. General Procedure B. Tryptophan methyl ester oxidation. In order to prevent methyl ester hydrolysis, a modified procedure is used for tryptophan methyl ester derivatives. The indole is dissolved in dimethyl sulfoxide (10 equiv) and glacial acetic acid (5 mL/mmol indole) is added, followed by dropwise addition of concentrated hydrochloric acid (12 N, 18 equiv) at ambient temperature. Reaction progress is monitored by LCMS and is typically complete in less than 30 minutes. The reaction mixture is neutralized (pH > 6) with concentrated ammonium hydroxide and extracted with dichloromethane. The combined organic phases are dried over sodium sulfate, filtered, and concentrated. The residue is purified by column chromatography to afford the oxindole product. General Procedure C. Oxindole Peroxidation. A schlenk tube is flame dried, cooled under a stream of argon gas, and charged with oxindole (1 equiv) and copper(I) chloride (0.1 equiv). The tube is sealed, then evacuated and backfilled with argon (three times). Dichloromethane (5 mL/mmol oxindole) is added, followed by dropwise addition of tert-butyl hydroperoxide (6 M in decane, 2 equiv). The reaction is stirred at ambient temperature, and monitored by LCMS. If the reaction is incomplete after 12 h, an additional portion of tert-butyl hydroperoxide (6 M in decane, 2 equiv) is added, and stirred for an additional 12 h. Upon completion, the reaction mixture is dry-loaded onto silica gel, and purified directly by column chromatography to afford the 3-(tert-butylperoxy)oxindole product.

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Oxidative Fragmentations and Skeletal Rearrangements of Oxindole Derivatives

et al. 2017

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“…In 2009 Stoltz and co-workers introduced an enantioselective protocol for their construction from substituted 3-bromooxindoles using a copper bisoxazoline catalyst (Scheme 8). 80,81 In the presence of an amine base, the bromide-bearing stereocenter at the 3-position of 65 is ablated, generating o-azaxylylene 66an extended π-electrophilethat is attacked by the Lewis acid-bound enolate. Chirality is transferred from the ligand to generate a variety of enantioenriched 3,3-disubstituted oxindole motifs (68).…”

Section: Enantioselective Protonationmentioning

confidence: 99%

Advances in Stereoconvergent Catalysis from 2005 to 2015: Transition-Metal-Mediated Stereoablative Reactions, Dynamic Kinetic Resolutions, and Dynamic Kinetic Asymmetric Transformations

et al. 2017

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An important subset of asymmetric synthesis is dynamic kinetic resolution, dynamic kinetic asymmetric processes and stereoablative transformations. Initially, only enzymes were known to catalyze dynamic kinetic processes but recently various synthetic catalysts have been developed. This review summarizes major advances in non-enzymatic, transition metal promoted dynamic asymmetric transformations reported between 2005 and 2015.

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“…After the reaction conditions were screened (see Table S1 in the Supporting Information for details), we were pleased to find that, with copper–bis(oxazoline) complex [Cu] as the catalyst and N , N -diisopropylethylamine (DIPEA) as the base, the reaction of 11 with dimethyl malonate in dichloromethane at −20 °C furnished the desired product (−)- 12 in 65% yield with 91% ee. The R -configuration of the quaternary all-carbon stereocenter was also firmly established on the basis of Stoltz’s report . Interestingly, our attempt to purify the compound by recrystallization in ethyl acetate/petroleum ether (1:10) revealed that the crystals were all racemic.…”

Section: Results and Discussionmentioning

confidence: 62%

“…The C2 side chain in A could be stitched by Suzuki coupling of the 3 H -indol-2-yl triflate derived from oxindole B . Finally, the all-carbon quaternary stereocenter in B could be introduced by copper-catalyzed enantioselective malonate addition to 3-bromooxindole C , an elegant method developed by the Stoltz group …”

Section: Results and Discussionmentioning

confidence: 99%

Enantioselective Total Synthesis of (+)-Corymine and (−)-Deformylcorymine

Zhang

Wang

2020

J. Am. Chem. Soc.

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We report herein the first enantioselective total synthesis of akuammiline alkaloids (+)-corymine and (−)-deformylcorymine. Starting from commercially available N-nosyltryptamine, the target molecules are both achieved in 11 steps. Key elements of the design include (a) a copper-catalyzed enantioselective addition of dimethyl malonate to a 3-bromooxindole to secure the C7 all-carbon quaternary stereocenter, (b) a one-step construction of cyclohexyl and pyrrolidinyl rings via intramolecular nucleophilic C-and N-addition, and (c) a nickel-promoted 7-endo cyclization of alkenyl bromide to furnish the azepanyl ring. The strategy is further extended to the synthesis of another three members of the akuammiline family, namely, (−)-10demethoxyvincorine, (−)-2(S)-cathafoline, and (−)-3-epi-dihydrocorymine 17-acetate.

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Stereochemical evaluation of bis(phosphine) copper catalysts for the asymmetric alkylation of 3-bromooxindoles with α-arylated malonate esters

Abstract: An improved method for the asymetric alkylation of 3-bromooxindoles with α-arylated malonate esters is described. The asymmetric alkylation demonstrated was achieved up to 70% ee utilizing a copper(II) bis(phosphine) complex.

Cited by 12 publications

References 58 publications

Oxidative Fragmentations and Skeletal Rearrangements of Oxindole Derivatives

Oxidative Fragmentations and Skeletal Rearrangements of Oxindole Derivatives

Advances in Stereoconvergent Catalysis from 2005 to 2015: Transition-Metal-Mediated Stereoablative Reactions, Dynamic Kinetic Resolutions, and Dynamic Kinetic Asymmetric Transformations

Enantioselective Total Synthesis of (+)-Corymine and (−)-Deformylcorymine

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