Palladium-Catalyzed Arylation/Heteroarylation of Indoles: Access to 2,3-Functionalized Indolines

Zeidan, Nicolas; Beisel, Tamara; Ross, Rachel; Lautens, Mark

doi:10.1021/acs.orglett.8b03310

Cited by 64 publications

(24 citation statements)

References 22 publications

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“…Several functional groups were tolerated at para-and meta-position. Different from previous Pd-catalysis 20 , in which the oxidative addition is sensitive to the steric hindrance, the methyl (25) and fluoro (27) groups at ortho-position of C-Br bond did not significantly affect the reaction, delivering the desired products in satisfactory yields. Moreover, difluoro (28) and dimethoxyl (29) substituents were also compatible.…”

Section: Resultscontrasting

confidence: 57%

“…Dearomative functionalization of indoles are particularly interesting to generate important indolines 15,16 . Although many methods have been developed in this field [17][18][19][20][21][22][23][24][25] , the dearomative reductive coupling of indoles with two electrophiles is still challenging due to the stability of carbon-carbon double bond within aromaticity and thus slow migratory insertion rate. In 2017, Qin et al realized an elegant Nicatalyzed asymmetric reductive hydroarylation of carbon-carbon double bond in indoles with water as proton source ( Fig.…”

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confidence: 99%

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Reductive dearomative arylcarboxylation of indoles with CO2 via visible-light photoredox catalysis

et al. 2020

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Catalytic reductive coupling of two electrophiles and one unsaturated bond represents an economic and efficient way to construct complex skeletons, which is dominated by transitionmetal catalysis via two electron transfer. Herein, we report a strategy of visible-light photoredox-catalyzed successive single electron transfer, realizing dearomative arylcarboxylation of indoles with CO 2. This strategy avoids common side reactions in transition-metal catalysis, including ipso-carboxylation of aryl halides and β-hydride elimination. This visible-light photoredox catalysis shows high chemoselectivity, low loading of photocatalyst, mild reaction conditions (room temperature, 1 atm) and good functional group tolerance, providing great potential for the synthesis of valuable but difficultly accessible indoline-3-carboxylic acids. Mechanistic studies indicate that the benzylic radicals and anions might be generated as the key intermediates, thus providing a direction for reductive couplings with other electrophiles, including D 2 O and aldehyde.

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Section: Resultscontrasting

confidence: 57%

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confidence: 99%

Reductive dearomative arylcarboxylation of indoles with CO2 via visible-light photoredox catalysis

et al. 2020

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“…A diastereoselective Pd-catalyzed dearomatization of the indole derivative 174 with the formation of the disubstituted indoline 175 was reported (Scheme 69), as a result of a 1,2-arylation/direct heteroarylation sequence, performing the reaction in the presence of benzothiazole (BTA). 70 The presence of CuCl 2 prevented the epimerization of the dibenzylic center and improved the conversion.…”

Section: Scheme 68 Spiroindoles By Pd-catalyzed Intramolecular Vinylamentioning

confidence: 99%

Pd-Catalyzed Domino Reactions Involving Alkenes To Access Substituted Indole Derivatives

et al. 2020

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Palladium-catalyzed domino reactions are advanced tools in achieving various nitrogen-containing heterocycles in an efficient and economical manner due to the reduced number of steps in the process. This review highlights recent advances in domino processes aimed at the synthesis of indole derivatives and polycyclic systems containing the indole nucleus in intra/intra- or intra/intermolecular reactions. In particular, we consider domino processes that involve a double bond in a step of the sequence, which allow the issue of regioselectivity in the cyclization to be faced and overcome. The different sections in this review focus on the synthesis of the indole nucleus and functionalization of the scaffold starting from different substrates that have been identified as activated starting materials, which involve a halogenated moiety or unactivated unsaturated systems. In the former case, the reaction is under Pd(0) catalysis, and in the second case a Pd(II) catalytic species is required and then an oxidant is necessary to reconvert the Pd(0) into the active Pd(II) species. On the other hand, the second method has the advantage that it uses easy available and inexpensive substrates.1 Introduction2 Indole Scaffold Synthesis2.1 Activated Substrates2.2 Unactivated Substrates3 Functionalization of Indole Scaffold3.1 Activated Substrates3.2 Unactivated Substrates4 Conclusions

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“…The intramolecular Heck arylation coupling reaction is among the most useful strategies for the construction of these compounds (Scheme 1) [11,21]. For example, isoindolo[2,1a]indoles 6 have been prepared by the annulation process through a Pd-or Ni-catalyzed coupling starting from the N-functionalized indoles 5 [11,19,21,[28][29][30]. On the other hand, the formation of pyrrolo [3,4-e]indoles 9/10 can be achieved via a Diels-Alder cyloaddition of 2-vinylpyrroles 8 with maleimides 7 [31][32][33][34][35].…”

Section: Introductionmentioning

confidence: 99%

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

Escalante

Martínez-Mora

Espinoza‐Hicks

et al. 2020

Beilstein J. Org. Chem.

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A highly regio-, chemo- and stereoselective divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles is herein described, starting from 2-formylpyrrole and employing Diels–Alder and Heck arylation reactions. 3-(N-Benzyl-2-pyrrolyl)acrylates and 4-(pyrrol-2-yl)butenones underwent a highly endo-Diels–Alder cycloaddition with maleimides to furnish octahydropyrrolo[3,4-e]indoles, which served as precursors in the regioselective synthesis of aza-polycyclic skeletons via an intramolecular Heck arylation reaction. Through the latter reaction, the 3-(N-benzyl-2-pyrrolyl)acrylates give rise to 3-(pyrrolo[2,1-a]isoindol-3-yl)acrylates. A further oxidative aromatization of the polycyclic intermediates provides the corresponding polycyclic pyrrolo-isoindoles and isoindolo-pyrrolo-indoles. A theoretical study on the stereoselective Diels–Alder reactions, carried out by calculating the endo/exo transition states, revealed the assistance of non-covalent interactions in governing the endo stereocontrol.

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Palladium-Catalyzed Arylation/Heteroarylation of Indoles: Access to 2,3-Functionalized Indolines

Cited by 64 publications

References 22 publications

Reductive dearomative arylcarboxylation of indoles with CO2 via visible-light photoredox catalysis

Reductive dearomative arylcarboxylation of indoles with CO2 via visible-light photoredox catalysis

Pd-Catalyzed Domino Reactions Involving Alkenes To Access Substituted Indole Derivatives

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

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