Oxidative electro-organic synthesis of dimeric hexahydropyrrolo-[2,3-<i>b</i>]indole alkaloids involving PCET: total synthesis of (±)-folicanthine

Shaw, K. B.; Sharma, Sulekha; Khatua, Arindam; Paul, Amit; Bisai, Alakesh

doi:10.1039/d1ob01463c

Cited by 8 publications

(13 citation statements)

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“…The pK a of the C−H proton of the pseudobenzylic position for 2a has been estimated to be ∼21 to 24, which is significantly higher than that of 1a (∼17 to 18), suggesting a significantly high energy requirement for the second electron transfer to generate a carbocation. 33 For the dimerization of 2a, the addition of base (NaH) was also required (vide supra). CVs of 2a also revealed an increase in current with increasing concentration of NaH, suggesting an involvement of base in the reaction mechanism (Figure 5a).…”

Section: Mechanism Of Dimerization Of 1a and Analogue Substratesmentioning

confidence: 99%

“…32 In recent time, we reported green electrochemical routes for dimerization of a variety of 2-oxindoles having the application for the total synthesis of dimeric hexahydropyrrolo [2,3-b] indole alkaloid, (±)-folicanthine, and so forth (Scheme 1c). 33,34 Interesting proton-coupled electron transfer (PCET) mechanisms were proposed, such as stepwise electron transfer (ET)−proton transfer (PT)−electron transfer (ET) or PT−ET−ET or ET− PT and so forth. 33,34 These syntheses were accomplished in metal and chemical oxidant-free mild reaction conditions.…”

Section: ■ Introductionmentioning

confidence: 99%

“…5 Besides, electrode passivation due to direct substrate oxidation at the electrode surface resulted in a long time for the completion of the reaction (1−4 h), and the applied current (or voltage) was high, suggesting high energy requirement to accomplish the reaction. 33,34 To overcome these challenges, in this work, instead of direct oxidation of 2-oxindoles on the electrode surface, oxidation of 2-oxindoles was performed using TEMPO [(2,2,6,6-tetramethylpiperidin-1-yl)oxyl)] as the redox mediator. TEMPOcatalyzed electrochemical oxidations of alcohols and amines are reported frequently in the literature; 9,35−40 however, only a few reports are available for the traditional organic molecules' transformations.…”

Section: ■ Introductionmentioning

confidence: 99%

“…More importantly, 3-alkyl-2-oxindoles show much higher oxidation potential than that of 3carboxylate-2-oxindoles (vide infra). 33,34 The reaction was attempted with the same condition by taking 2a as the substrate (Scheme 3); however, the dimeric product was not obtained. Therefore, the reaction conditions were further optimized by addition of different concentrations of base, that is, NaH (Table S2, Supporting Information).…”

Section: ■ Introductionmentioning

confidence: 99%

“…The major disadvantage was a large amount of waste generation because of massive electrolyte usage, which distances it from one of the principles of green chemistry . Besides, electrode passivation due to direct substrate oxidation at the electrode surface resulted in a long time for the completion of the reaction (1–4 h), and the applied current (or voltage) was high, suggesting high energy requirement to accomplish the reaction. , …”

Section: Introductionmentioning

confidence: 99%

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Two-Electron- and One-Electron-Transfer Pathways for TEMPO-Catalyzed Greener Electrochemical Dimerization of 3-Substituted-2-Oxindoles

et al. 2023

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Dimerized 3-substituted 2-oxindoles are essential building blocks for the total synthesis of alkaloids. Herein, three different types of 3-substituted-2-oxindoles were dimerized with a total of 41 examples employing TEMPO as a redox mediator and TEMPO+ as an in situ generated electrocatalyst using control potential electrolysis at an applied potential of only 0.8 V versus a Ag/Ag+ nonaqueous reference electrode. These reactions did not yield any product formation in the absence of TEMPO, keeping other experimental conditions the same. Two-electron- and one-electron-transfer pathways were operational depending on the oxidation potentials of 2-oxindoles. 3-Carboxylate-2-oxindoles having a lower oxidative energy barrier for a two-electron-transfer pathway followed a hydride-transfer mechanism to generate a carbocation, which thereafter reacted with the enol form of oxindole to produce dimerized 2-oxindoles. On the other hand, 3-alkyl-2-oxindoles and 3-alkylcarboxylate-2-oxindoles had significantly higher oxidative energy barrier compared to 3-carboxylate-2-oxindoles and followed the one-electron-transfer pathway to generate a radical species for dimerization. The two-electron transfer pathway was significantly faster compared to the one-electron transfer pathway, evident from reaction time (15 min vs 1 h 20 min or longer), which was due to a faster second-order rate constant for the two-electron transfer pathway (1.2 M–1 s–1) compared to the one-electron transfer pathway (0.29 M–1 s–1). Furthermore, four aspects of transforming greener electro-organic synthesis have been demonstrated. They are as follows: (a) electron-transfer rate measurement as an alternative method for synthesis optimization instead of lengthy product isolation, (b) prevention of electrode passivation employing electrocatalysis routes, (c) recovery of the electrolyte, and (d) mild reaction conditions employing control potential electrolysis. Finally, an efficient electrochemical oxidation strategy has been demonstrated for the total synthesis of a dimeric hexahydropyrrolo[2,3-b]indole alkaloids, (±)-chimonanthine (I) and (±)-folicanthine (II).

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Section: Mechanism Of Dimerization Of 1a and Analogue Substratesmentioning

confidence: 99%