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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:
Research Org.:
Stanford Univ., CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1675014
Alternate Identifier(s):
OSTI ID: 1817112; OSTI ID: 1972325
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. doi: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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