Pd-Catalyzed Asymmetric Dearomatization of Indoles via Decarbonylative Heck-Type Reaction of Thioesters

Organic Letters, Journal Year: 2020, Volume and Issue: 23(1), P. 172 - 177

Published: Dec. 18, 2020

We report herein a palladium-catalyzed ligand-promoted asymmetric dearomatization of indoles via the decarbonylation thioesters and subsequent reductive Heck reaction. This protocol provides facile efficient way to construct an aza-quaternary stereocenter at C2 position indolines. A variety functional groups substitutions could be well tolerated, affording substituted indolines with high enantioselectivities.

Language: Английский

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Spirocyclizative Remote Arylcarboxylation of Nonactivated Arenes with CO ₂ via Visible-Light-Induced Reductive Dearomatization

CCS Chemistry, Journal Year: 2021, Volume and Issue: 4(5), P. 1565 - 1576

Published: May 28, 2021

Open AccessCCS ChemistryCOMMUNICATION1 May 2022Spirocyclizative Remote Arylcarboxylation of Nonactivated Arenes with CO2 via Visible-Light-Induced Reductive Dearomatization Yuzhen Gao, Hao Wang, Zhuomin Chi, Lei Yang, Chunlin Zhou and Gang Li Gao Key Laboratory Coal to Ethylene Glycol Its Related Technology, Center for Excellence in Molecular Synthesis, Fujian Institute Research on the Structure Matter, University Chinese Academy Sciences, Fuzhou, 350002 , Wang Chi College Chemistry Materials Science, Normal University, 350117 Yang *Corresponding author: E-mail Address: [email protected] Frontiers Science Transformative Molecules, Shanghai Jiao Tong 200240 https://doi.org/10.31635/ccschem.021.202100995 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Visible-light-induced reductive dearomatization nonactivated arenes is a very challenging transformation remains its infancy. Herein, we report novel strategy achieve visible-light-induced spirocyclizative remote arylcarboxylation including naphthalenyl- phenyl-bearing aromatics under mild conditions through radical-polar crossover cascade (RPCC). This protocol rapidly delivers broad range spirocyclic valuable carboxylic acid derivatives from readily accessible aromatic precursors generally good regioselectivity chemoselectivity. Download figure PowerPoint Introduction represents unique synthetic that converts available planar into three-dimensional alicyclic molecules.1–6 Notable methods include Birch reduction,7 transition-metal-catalyzed dearomative functionalization,8,9 oxidative electron-rich (hetero)aromatics,10 UV-light-promoted photochemical cycloadditions.11 However, progress has mainly been made studies heteroaromatics indoles, such as phenols naphthols.1–24 In contrast, only limited important advances have electronically unbiased naphthalene benzene possess high resonance stabilization energy.6,25–35 Of particular note, You group25 Hong Jia's group26 simultaneously reported two types elegant, highly diastereoselective 1,4-difunctionalization reactions 1-naphthamides palladium-catalyzed at slightly elevated temperature. Therefore, challenging, development complementary desirable. recent years, visible-light photoredox catalysis36–45 emerged promising developing protocols dearomatization,46–59 several significant arenes,60–74 cycloadditions were groups Sarlah Bach,60–63 dearomatization.64–66 A distinct redox-neutral hydroalkylative was also by group Zhang, Mei, You.67 there are handful reports arenes.68–74 König68 Miyake69 independently catalyst (PC)-induced Birch-type reduction arenes. Meanwhile, monofunctionalizations hydroalkylation70–72 hydroboration73 photoreduction disclosed Stephenson,70 Murakami,71 Curran,73 respectively (Scheme 1a). Notably, Jui group74 achieved hydroarylation using an amine reductant 1a), avoiding use toxic reagents SmI2/hexamethylphosphoramide (HMPA)75 similar traditional transformations. Despite this progress, difunctionalization possibly due competing protonation rearomatization. Scheme 1 | (a–c) More recently, our group76 styrenes (RPCC), which initiated reactive aryl radicals generated halides. We wondered whether RPCC process76–91 could be applied CO2. during investigation, Yu group92 2,3-arylcarboxylation class well-studied heteroarene reactions, 5-exo-trig cyclization 1b). Surprisingly, chemoselective phenyl ring 6-exo-trig occurred 2-phenyl indoles substates reaction conditions, leading products those Yu's work 1c). line continuous interest catalytic utilization CO2,93,94 abundant, low-cost, sustainable, nontoxic C1 building block, herein bearing naphthalenyl, phenyl, quinolinyl provides rapid access valuable, complex, frameworks type Hantzsch ester reaductant, is, 4-potassium carboxylate HE (4-CO2K-HE), discovered study. Results Discussion To start derivative 1a (Table 1) utilized model substrate, irradiated 30 W blue light-emitting diodes (LEDs) presence commercially PC Ru(bpy)3Cl2 atmospheric pressure ambient After extensive screening 1,4-arylcarboxylation product 2, methylated original ease isolation, obtained 83% isolated yield employing 4-CO2K-HE reductant95–97 K2CO3 base dimethylformamide (DMF; entry 1). The structure 2 confirmed X-ray analysis, representing formal C–H carboxylation CO2.98–100 Control revealed no observed without either or light, indicating promoted light (entries 3). decrease when carrying out nitrogen atmosphere (entry 4), suggesting some produced oxidation 4-CO2K-HE. detected addition 5), much better than other reductants (HEH), N,N-diisopropylethylamine (DIPEA), Et3N, revealing critical role 6–8). desired HCO2K, contrast previous 9).76 decreased dramatically carried Cs2CO3 absence 10 11). PCs 2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile (4CzIPN) iridium complexes, proved most suitable one 12–14). Slight loading reduced mol % 15). Moreover, solvents examined, DMF found best comparing dimethyl sulfoxide (DMSO), N,N-dimethylacetamide (DMA), CH3CN 16–18). Finally, bromide chloride analog employed starting material recovered 19 20). Table Optimization Reaction Conditionsa Entry Deviation Standard Conditions Yield (%)b None 87 (83)c Without N.D. 3 dark 4 Under 37 5 6 HEH (2.0 equiv) 61 7 DIPEA 18 8 Et3N(2.0 9 HCO2K instead 11 41 12 4CzIPN 45 13 [Ir(ppy)2(dtbbpy)]PF6 14 fac-Ir(ppy)3 15 (2 %) 73 16 DMSO 60 17 DMA 74 Br I 20 Cl Note: N.D., not detected; 4-CO2K-HE, potassium 3,5-bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carboxylate HE; HEH, ester; bpy, 2,2′-bipyridine; ppy, 2-phenylpyridine; dtbbpy, 4,4-di-tert-butyl-2,2′-bipyridine. aReaction conditions: (0.1 mmol), (3 %), (0.12 mmol, 1.2 equiv), (0.2 2.0 (1 mL), atm CO2, rt, 24 h, LEDs; then MeI (0.5 °C, h. bYield determined 1H NMR CH2Br2 internal standard. cYield parentheses 0.2 mmol scale. optimized tested series quinoline investigate generality arylcarboxylation. As shown phenol ether linker various functional groups, halide (F, Cl, Br) CO2Me, afforded corresponding dearomatized yields ( 2– 7). Substrates possessing or/and pyridyl compatible produce structurally diverse heterocycles 8– addition, N-protected aniline linkers different protecting (such Boc, Ac, Cbz, CO2Ph) tolerated 12– substitution patterns allowed give satisfied 16– 21). spiroindolines delivered substrates 22 23). trace amounts side competitive substrates, except less 5% 23. Scope naphthalenes quinolines (0.24 (0.4 (1.0 Isolated yields. aMethylation SOCl2 MeOH (4 100 Subsequently, versatility spiro-dearomative process studied 3).25 Pleasingly, N-alkyl methyl, benzyl, isopropyl) reaction, delivering 25– 27 (73–76%). electron-donating (Me OMe), electron-withdrawing (halides, CF3, CN) meta para position all affording (28–38, 60–75%). Substrate methyl C6 gave 39 64% yield. substrate viable transformation, providing target 40 acceptable C4 naphthalenyl tolerated, producing 4-carboxylated 41– 43) reasonable yields, though about 10% these examples. aYield major diastereomer, minor diastereomer isolated. Furthermore, explored 2-tethered 4). after being subjected led 1,2-arylcarboxylation 45– 48) whose structures above-mentioned 1-tethered naphthalenes, albeit moderate 1,2-hydroarylation (10–20%) substrates. Importantly, approach dearomatize benzamide rings 49– 53), scope phenanthridin-6-one 49 50, unknown 51– 53. 44 48 aStructure displayed; 10–20% observed. b24 During study, surprisingly unexpected reactivity 5). Interestingly, predominantly rather activated indole ring's C2–C3 double bond study same substrate.92 55 carboxylation.98–100 rationale chemoselectivity clear present. Initially, iodide employed, but it effective 55). It should mentioned lower 55. suspected might labile, resulting relatively Gratifyingly, substituents converted (56–65). indole's bond, debromination (about 5%) well (generally <5%) noted unreacted transformed unidentifiable decomposed. amide since substate 2-bromobenzyl 2-bromobenzamide group. 54 LEDs, h; yields; a2 moved conduct preliminary mechanistic obtain insight mechanism. First, Stern–Volmer luminescence experiments showed light-activated Ru (PC*) quenched effectively 54a (see Supporting Information details). determine carboxyl source product, 13CO2 (99% 13C) gas 88% 13C incorporation 6a). isotope-labeling diene d- 66 suggested possible anion intermediate 6b). radical trapping performed, 1,1-diphenyl ethylene 2,2,6,6-tetramethylpiperidinooxy (TEMPO), identifiable trapped, TEMPO probably suppressed oxidizing Information). scaled up 6c). derivation briefly generate 67 allylic alcohol 68 6d). (a–d) Mechanistic studies, scale-up derivation. mechanism proposed based above Upon irradiation, excited PC* A) subsequently reductively (E = −0.90 V vs. saturated calomel electrode (SCE) DMF, see Information) B) (E1/2 [RuII*/RuI] +0.77 vs SCE MeCN)101 dihydropyridine C) release Reduction B [RuI/RuII] −1.33 D underwent afford E. Single-electron transfer C E anionic G, nucleophilic H. base-promoted rearrangement followed methylation Proposed cycle. Conclusion developed novel, N-benzylanilines RPCC. An interesting unusual presented. dearomatization/arylcarboxylation efficiently precursors, method complex molecule construction. available, general experimental procedures characterization spectra. Conflict Interest authors declare financial interest. Preprint Statement presented article posted preprint server ChemRxiv prior publication CCS Chemistry. can here: [DOI: http://dx.doi.org/10.26434/chemrxiv.14449728]. Acknowledgments gratefully acknowledge support NSFC (grant nos. 21871257, 22022111, 21801240), Natural Foundation Province no. 2020J02008), Strategic Priority Program Sciences XDB20000000). thank Weiping Cai FJIRSM help cyclic voltammetry experiment Tao Shaoxing crystallographic structural data analysis. References 1. Roche S. P.; Porco J. A.Dearomatization Strategies Synthesis Complex Products.Angew. Chem. Int. Ed.2011, 4068–4093. Google Scholar 2. Zhuo C.-X.; Zhang W.; S.-L.Catalytic Asymmetric Reactions.Angew. Ed.2012, 51, 12662–12686. 3. Zheng C.; S.-L.Transition-Metal-Catalyzed Allylic Reactions.Acc. Res.2014, 47, 2558–2573. 4. James M. J.; O'Brien Taylor R. K.; Unsworth W. P.Synthesis Spirocyclic Indolenines.Chem. Eur. J.2016, 22, 2856–2881. 5. Bariwal Voskressensky L. G.; Van der Eycken V.Recent Advances Spirocyclization Indole Derivatives.Chem. Soc. Rev.2018, 3831–3848. 6. Wertjes Southgate H.; D.Recent Chemical Arenes.Chem. 7996–8017. 7. A. J.Reduction Dissolving Metals. 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Language: Английский

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Photoredox Asymmetric Nucleophilic Dearomatization of Indoles with Neutral Radicals

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(2), P. 998 - 1007

Published: Jan. 6, 2021

The dearomatization of indoles represents the most efficient approach for accessing highly valued indolines. inherent nucleophilic reactivity has dictated indole development in both 1e– and 2e– processes. However, electron-deficient been challenging. Herein, we introduce a conceptually distinct photoredox-mediated Giese-type transformation strategy, which is generally used conjugate addition radicals to simple α, β-unsaturated systems, chemoselectively breaking C═C bonds embedded aromatic structure. Moreover, diastereoselective challenging neutral achieved by Oppolzer camphorsultam chiral auxiliary. Structurally diverse amine-functionalized indolines carrying functional stereochemical diversity are produced from wide array amines as radical precursors. Furthermore, mild, powerful manifold capable late-stage modification complex natural products pharmaceuticals. DFT studies performed elucidate observed outcomes.

Language: Английский

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Dearomative (3+2) Cycloadditions between Indoles and Vinyldiazo Species Enabled by a Red‐Shifted Chromium Photocatalyst

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(45)

Published: Sept. 5, 2022

A direct dearomative photocatalyzed (3+2) cycloaddition between indoles and vinyldiazo reagents is described. The transformation enabled by the development of a novel oxidizing Cr

Language: Английский

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Recent Advances in the Synthesis of Indolines via Dearomative Annulation of N‐acylindoles

Asian Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 11(10)

Published: Aug. 3, 2022

Abstract Polycyclic fused indoline derivatives, specifically those bearing tertiary or quaternary carbon stereocenters at C2 and C3 positions, stand as an important class of nitrogen‐containing heterocyclic compounds because they are frequently occurring core structures in a wide variety alkaloid natural products, pharmaceutical molecules, functional materials. Over the past few decades, development new versatile synthetic approaches for construction indolines has been focus great deal research initiatives. In this review, recent advances dearomative annulation N‐ acylindoles with diverse nucleophiles summarized since 2012, which could be divided into five categories: 1) Dearomative Heck reactions acylindoles; 2) Visible‐light‐induced reductive dearomatization 3) Lewis acid‐catalyzed 4) Asymmetric 5) by other closely related reagents.

Language: Английский

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Photoredox-Catalyzed Intermolecular Hydroalkylative Dearomatization of Electron-Deficient Indole Derivatives

Organic Letters, Journal Year: 2020, Volume and Issue: 22(24), P. 9699 - 9705

Published: Dec. 9, 2020

Dearomatization of indole derivatives offers a straightforward approach to access diverse indolines. To date, the corresponding dearomative transformations involving electron-deficient indoles are limited. Herein, we report one-electron strategy for dearomatization via photoredox-catalyzed hydroalkylation employing commercially available glycine as hydrofunctionalization reagents. Followed by DBU-mediated lactamization, structurally appealing lactam-fused indolines obtained in good excellent yields with exclusive selectivity.

Language: Английский

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Visible-light induced divergent dearomatization of indole derivatives: controlled access to cyclobutane-fused polycycles and 2-substituted indolines

Organic Chemistry Frontiers, Journal Year: 2020, Volume and Issue: 8(2), P. 319 - 325

Published: Nov. 20, 2020

A visible-light-induced catalytic, divergent dearomative functionalization of indole derivatives is achieved, thereby leading to the formation cyclobutane-fused polycycles and 2-substituted indolines in a controllable fashion.

Language: Английский

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Photoinduced Dearomatizing Three‐Component Coupling of Arylphosphines, Alkenes, and Water

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 60(7), P. 3551 - 3555

Published: Oct. 21, 2020

Abstract A unique photoinduced reaction that couples a triarylphosphine, an alkene, and water to produce 2‐(cyclohexa‐2,5‐dienyl)ethylphosphine oxide is reported herein. The alkene inserts into C(aryl)−P bond of the arylphosphine, aryl ring dearomatized cyclohexadienyl ring, phosphorus oxidized. three components are all readily available, their intermolecular coupling significantly increases molecular complexity. products formed applicable Wittig olefination.

Language: Английский

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Organophotocatalytic dearomatization of indoles, pyrroles and benzo(thio)furans via a Giese-type transformation

Communications Chemistry, Journal Year: 2021, Volume and Issue: 4(1)

Published: Feb. 19, 2021

Accessing fascinating organic and biological significant indolines via dearomatization of indoles represents one the most efficient approaches. However, it has been difficult for electron deficient indoles. Here we report studies leading to developing a photoredox mediated Giese-type transformation strategy The reaction implemented chemoselectively breaking indolyl C=C bonds embedded in aromatic system. synthetic power this demonstrated by using structurally diverse bearing common electron-withdrawing groups including (thio)ester, amide, ketone, nitrile even aromatics at either C

Language: Английский

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A Versatile Enantioselective Catalytic Cyclopropanation‐Rearrangement Approach to the Divergent Construction of Chiral Spiroaminals and Fused Bicyclic Acetals

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(43), P. 18964 - 18969

Published: July 17, 2020

A highly enantioselective synthesis of various chiral heterobicyclic molecules including spiroaminals and fused bicyclic acetals has been developed via a copper catalyzed cyclopropanation-rearrangement (CP-RA) approach under mild reaction conditions. Remarkably, the asymmetric CP-RA for exocyclic vinyl substrates without pro-stereogenic carbon at β-position realized first time broad substrate scope with excellent results (33 examples; 34-99 % yields; >95/5 dr 91-99 ee) achieved. An application successive was also described, providing concise access to complex heteropolycycles.

Language: Английский

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