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Title: Carbonate-promoted C–H carboxylation of electron-rich heteroarenes

Abstract

C–H carboxylation is an attractive transformation for both streamlining synthesis and valorizing CO2. The high bond strength and very low acidity of most C–H bonds, as well as the low reactivity of CO2, present fundamental challenges for this chemistry. Conventional methods for carboxylation of electron-rich heteroarenes require very strong organic bases to effect C–H deprotonation. Here we show that alkali carbonates (M2CO3) dispersed in mesoporous TiO2 supports (M2CO3/TiO2) effect CO32- promoted C–H carboxylation of thiophene- and indole-based heteroarenes in gas–solid reactions at 200–320 C. M2CO3/TiO2 materials are strong bases in this temperature regime, which enables deprotonation of very weakly acidic bonds in these substrates to generate reactive carbanions. In addition, we show that M2CO3/TiO2 enables C3 carboxylation of indole substrates via an apparent electrophilic aromatic substitution mechanism. No carboxylations take place when M2CO3/TiO2 is replaced with un-supported M2CO3, demonstrating the critical role of carbonate dispersion and disruption of the M2CO3 lattice. After carboxylation, treatment of the support-bound carboxylate products with dimethyl carbonate affords isolable esters and the M2CO3/TiO2 material can be regenerated upon heating under vacuum. Our results provide the basis for a closed cycle for the esterification of heteroarenes with CO2 and dimethyl carbonate.

Authors:
 [1]; ORCiD logo [1]
  1. Department of Chemistry, Stanford University, Stanford, USA
Publication Date:
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1675014
Alternate Identifier(s):
OSTI ID: 1817112
Grant/Contract Number:  
SC0020394
Resource Type:
Published Article
Journal Name:
Chemical Science
Additional Journal Information:
Journal Name: Chemical Science Journal Volume: 11 Journal Issue: 43; Journal ID: ISSN 2041-6520
Publisher:
Royal Society of Chemistry (RSC)
Country of Publication:
United Kingdom
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Porter, Tyler M., and Kanan, Matthew W.. Carbonate-promoted C–H carboxylation of electron-rich heteroarenes. United Kingdom: N. p., 2020. Web. https://doi.org/10.1039/D0SC04548A.
Porter, Tyler M., & Kanan, Matthew W.. Carbonate-promoted C–H carboxylation of electron-rich heteroarenes. United Kingdom. https://doi.org/10.1039/D0SC04548A
Porter, Tyler M., and Kanan, Matthew W.. Wed . "Carbonate-promoted C–H carboxylation of electron-rich heteroarenes". United Kingdom. https://doi.org/10.1039/D0SC04548A.
@article{osti_1675014,
title = {Carbonate-promoted C–H carboxylation of electron-rich heteroarenes},
author = {Porter, Tyler M. and Kanan, Matthew W.},
abstractNote = {C–H carboxylation is an attractive transformation for both streamlining synthesis and valorizing CO2. The high bond strength and very low acidity of most C–H bonds, as well as the low reactivity of CO2, present fundamental challenges for this chemistry. Conventional methods for carboxylation of electron-rich heteroarenes require very strong organic bases to effect C–H deprotonation. Here we show that alkali carbonates (M2CO3) dispersed in mesoporous TiO2 supports (M2CO3/TiO2) effect CO32- promoted C–H carboxylation of thiophene- and indole-based heteroarenes in gas–solid reactions at 200–320 C. M2CO3/TiO2 materials are strong bases in this temperature regime, which enables deprotonation of very weakly acidic bonds in these substrates to generate reactive carbanions. In addition, we show that M2CO3/TiO2 enables C3 carboxylation of indole substrates via an apparent electrophilic aromatic substitution mechanism. No carboxylations take place when M2CO3/TiO2 is replaced with un-supported M2CO3, demonstrating the critical role of carbonate dispersion and disruption of the M2CO3 lattice. After carboxylation, treatment of the support-bound carboxylate products with dimethyl carbonate affords isolable esters and the M2CO3/TiO2 material can be regenerated upon heating under vacuum. Our results provide the basis for a closed cycle for the esterification of heteroarenes with CO2 and dimethyl carbonate.},
doi = {10.1039/D0SC04548A},
journal = {Chemical Science},
number = 43,
volume = 11,
place = {United Kingdom},
year = {2020},
month = {11}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1039/D0SC04548A

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Works referenced in this record:

A closed cycle for esterifying aromatic hydrocarbons with CO2 and alcohol
journal, August 2019


Carboxylation of Phenols with CO 2 at Atmospheric Pressure
journal, March 2016

  • Luo, Junfei; Preciado, Sara; Xie, Pan
  • Chemistry - A European Journal, Vol. 22, Issue 20
  • DOI: 10.1002/chem.201601114

EtAlCl 2 /2,6-Disubstituted Pyridine-Mediated Carboxylation of Alkenes with Carbon Dioxide
journal, May 2016


C–H carboxylation of heteroarenes with ambient CO 2
journal, January 2016

  • Fenner, Sabine; Ackermann, Lutz
  • Green Chemistry, Vol. 18, Issue 13
  • DOI: 10.1039/C6GC00200E

Flash carboxylation: fast lithiation–carboxylation sequence at room temperature in continuous flow
journal, January 2014

  • Pieber, Bartholomäus; Glasnov, Toma; Kappe, C. O.
  • RSC Advances, Vol. 4, Issue 26
  • DOI: 10.1039/c4ra01442a

Photoredox activation of carbon dioxide for amino acid synthesis in continuous flow
journal, December 2016

  • Seo, Hyowon; Katcher, Matthew H.; Jamison, Timothy F.
  • Nature Chemistry, Vol. 9, Issue 5
  • DOI: 10.1038/nchem.2690

A scalable carboxylation route to furan-2,5-dicarboxylic acid
journal, January 2017

  • Dick, Graham R.; Frankhouser, Amy D.; Banerjee, Aanindeeta
  • Green Chemistry, Vol. 19, Issue 13
  • DOI: 10.1039/C7GC01059A

Phase Behavior That Enables Solvent-Free Carbonate-Promoted Furoate Carboxylation
journal, August 2020


C−H Carboxylation of Aromatic Compounds through CO 2 Fixation
journal, August 2017


Green halogenation reactions for (hetero)aromatic ring systems in alcohol, water, or no solvent
journal, December 2018

  • Kajorinne, Jessie K.; Steers, Jennifer C. M.; Merchant, Marnie E.
  • Canadian Journal of Chemistry, Vol. 96, Issue 12
  • DOI: 10.1139/cjc-2018-0259

Photoredox Catalysis as a Strategy for CO 2 Incorporation: Direct Access to Carboxylic Acids from a Renewable Feedstock
journal, February 2019


Carbonate-Promoted Hydrogenation of Carbon Dioxide to Multicarbon Carboxylates
journal, April 2018


Synthesis and anticancer activity of 5-(3-indolyl)-1,3,4-thiadiazoles
journal, October 2010

  • Kumar, Dalip; Maruthi Kumar, N.; Chang, Kuei-Hua
  • European Journal of Medicinal Chemistry, Vol. 45, Issue 10
  • DOI: 10.1016/j.ejmech.2010.07.023

Acidity measurements in THF. V. Heteroaromatic compounds containing 5-membered rings
journal, December 1985

  • Fraser, Robert R.; Mansour, Tarek S.; Savard, Sylvain
  • Canadian Journal of Chemistry, Vol. 63, Issue 12
  • DOI: 10.1139/v85-574

Me2AlCl-mediated carboxylation, ethoxycarbonylation, and carbamoylation of indoles
journal, February 2016


Carbon Dioxide as the C1 Source for Direct C−H Functionalization of Aromatic Heterocycles
journal, August 2010

  • Vechorkin, Oleg; Hirt, Nathalie; Hu, Xile
  • Organic Letters, Vol. 12, Issue 15
  • DOI: 10.1021/ol101450u

Rhodium(I)-Catalyzed Direct Carboxylation of Arenes with CO 2 via Chelation-Assisted C−H Bond Activation
journal, February 2011

  • Mizuno, Hajime; Takaya, Jun; Iwasawa, Nobuharu
  • Journal of the American Chemical Society, Vol. 133, Issue 5
  • DOI: 10.1021/ja109097z

C−H Bond Carboxylation with Carbon Dioxide
journal, December 2018


Carboxylic Acids as Substrates in Homogeneous Catalysis
journal, April 2008

  • Gooßen, Lukas J.; Rodríguez, Nuria; Gooßen, Käthe
  • Angewandte Chemie International Edition, Vol. 47, Issue 17
  • DOI: 10.1002/anie.200704782

Ligand-enabled site-selectivity in a versatile rhodium(ii)-catalysed aryl C–H carboxylation with CO2
journal, June 2018


Using Carbon Dioxide as a Building Block in Continuous Flow Synthesis
journal, November 2018

  • Seo, Hyowon; Nguyen, Long V.; Jamison, Timothy F.
  • Advanced Synthesis & Catalysis, Vol. 361, Issue 2
  • DOI: 10.1002/adsc.201801228

Efficient Chemoselective Carboxylation of Aromatics to Arylcarboxylic Acids with a Superelectrophilically Activated Carbon Dioxide−Al 2 Cl 6 /Al System
journal, September 2002

  • Olah, George A.; Török, Béla; Joschek, Jens P.
  • Journal of the American Chemical Society, Vol. 124, Issue 38
  • DOI: 10.1021/ja020787o

Direct carboxylation of simple arenes with CO 2 through a rhodium-catalyzed C–H bond activation
journal, January 2014

  • Suga, Takuya; Mizuno, Hajime; Takaya, Jun
  • Chem. Commun., Vol. 50, Issue 92
  • DOI: 10.1039/C4CC06188H

Polyamide monomers via carbonate-promoted C–H carboxylation of furfurylamine
journal, January 2020

  • Lankenau, Andrew W.; Kanan, Matthew W.
  • Chemical Science, Vol. 11, Issue 1
  • DOI: 10.1039/C9SC04460D

Carbon dioxide utilization via carbonate-promoted C–H carboxylation
journal, March 2016

  • Banerjee, Aanindeeta; Dick, Graham R.; Yoshino, Tatsuhiko
  • Nature, Vol. 531, Issue 7593
  • DOI: 10.1038/nature17185

Ni-Catalyzed Direct Carboxylation of an Unactivated C–H Bond with CO 2
journal, August 2020


Selective mono- or dimetalation of arenes by means of superbasic reagents
journal, January 1990


Photocarboxylation of Benzylic C–H Bonds
journal, July 2019

  • Meng, Qing-Yuan; Schirmer, Tobias E.; Berger, Anna Lucia
  • Journal of the American Chemical Society, Vol. 141, Issue 29
  • DOI: 10.1021/jacs.9b05360

π-Nucleophilicity in Carbon−Carbon Bond-Forming Reactions
journal, January 2003

  • Mayr, Herbert; Kempf, Bernhard; Ofial, Armin R.
  • Accounts of Chemical Research, Vol. 36, Issue 1
  • DOI: 10.1021/ar020094c

On the Interpretation of Deuterium Kinetic Isotope Effects in CH Bond Functionalizations by Transition-Metal Complexes
journal, March 2012

  • Simmons, Eric M.; Hartwig, John F.
  • Angewandte Chemie International Edition, Vol. 51, Issue 13
  • DOI: 10.1002/anie.201107334

What are the pKa values of C–H bonds in aromatic heterocyclic compounds in DMSO?
journal, February 2007


Metal-Catalyzed Carboxylation of Organic (Pseudo)halides with CO 2
journal, September 2016


Carboxylation of Benzylic and Aliphatic C–H Bonds with CO 2 Induced by Light/Ketone/Nickel
journal, November 2019

  • Ishida, Naoki; Masuda, Yusuke; Imamura, Yuuya
  • Journal of the American Chemical Society, Vol. 141, Issue 50
  • DOI: 10.1021/jacs.9b12529

Base-Mediated Carboxylation of Unprotected Indole Derivatives with Carbon Dioxide
journal, September 2012

  • Yoo, Woo-Jin; Capdevila, Montse Guiteras; Du, Xiangwei
  • Organic Letters, Vol. 14, Issue 20
  • DOI: 10.1021/ol3025082

Electrophilic Allylations and Benzylations of Indoles in Neutral Aqueous or Alcoholic Solutions
journal, October 2006

  • Westermaier, Martin; Mayr, Herbert
  • Organic Letters, Vol. 8, Issue 21
  • DOI: 10.1021/ol0618555

Lithium tert-Butoxide-Mediated Carboxylation Reactions of Unprotected Indoles and Pyrroles with Carbon Dioxide
journal, January 2015

  • Kobayashi, Shū; Yoo, Woo-Jin; V. Q. Nguyen, Thanh
  • HETEROCYCLES, Vol. 90, Issue 2
  • DOI: 10.3987/COM-14-S(K)94