Heck and Sonogashira couplings in aqueous media – application to unprotected nucleosides and nucleotides

Amongst all synthetic nucleosides having high potential biological activities, C5-modified pyrimidines and C7-deaza or C8-modified purines have been particularly studied. These main chemical modifications have been developed using palladium cross-coupling reactions. This review focus on both Heck and Sonogashira cross-coupling of nucleosides using different aspects of the twelve principles of green chemistry: use of aqueous medium and no protection/deprotection steps.

Heck cross-coupling reaction in aqueous solution was developed using only Pd(II) as a pre-catalyst in water and in CH₃CN/H₂O.
The first Heck cross-coupling reaction starting from deprotected nucleoside was reported in 1998 by Barbas et al. [16]. Starting from 5-iodo-2’-deoxyuridine (1) and allyl amide 2 in presence of Na₂PdCl₄ (80 mol%) as palladium source in sodium acetate buffer (0.1 M, pH = 5.2) as solvent at room temperature for 18 hours, (E)-[3-(trifluoroacetamido)propenyl]-2’-deoxyuridine (3) was isolated in 44% yield (Scheme 1). Compound 3 is a precursor of functionalized dUTP derivatives that are substrates for thermostable DNA polymerases. Nucleoside analogue 3 was obtained a few years later in the same range of yields by Williams et al. using the same experimental conditions[17].

Scheme 2
Synthesis of ferrocene analogue 65 and 66.

Scheme 3
Synthesis of phenylalanine analogues 67 and 68.

Heck and Sonogashira couplings in aqueous media – application to unprotected nucleosides and nucleotides

Gwénaëlle Hervé¹ and Christophe Len^12*

• *Corresponding author: Christophe Len christophe.len@utc.fr
• 

¹Université de Technologie de Compiègne, Ecole Supérieure de Chimie Organique et Minérale, EA4297, Centre de recherche de Royallieu, Compiègne Cedex, BP20529, F-60205, France

²Department of Chemistry, University of Hull, England HU6 7RX, UK

Sustainable Chemical Processes 2015, 3:3  doi:10.1186/s40508-015-0029-2

The electronic version of this article is the complete one and can be found online at:http://www.sustainablechemicalprocesses.com/content/3/1/3
http://www.sustainablechemicalprocesses.com/content/3/1/3

 

• 
  Université de Technologie de Compiègne

  Transformations Intégrées de la Matière Renouvelable (TIMR) - EA 4297

  Compiègne, France

LEN Christophe
Head of Research, Scientific Council

 

 https://www.researchgate.net/profile/Christophe_Len/info

RESEARCH EXPERIENCE

• Sep 2012–present,Honorary Professor
  University of Hull · Department of Chemistry
  United Kingdom · Hull
• Sep 2008–present,Professor (Full)
  Université de Technologie de Compiègne · Transformations Intégrées de la Matière Renouvelable (TIMR) - EA 4297
  France · Compiègne
• Sep 2004–Sep 2008,Professor (Full)
  Université de Poitiers · Département de Chimie (IUTP)
  France · Poitiers
• Sep 1997–Aug 2004, Professor (Assistant),Université de Picardie Jules Verne · LG - Laboratoire des glucides
  France · Amiens

 Centre de recherche de Royallieu, Compiègne Cedex

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///////Heck, Sonogashira, Green chemistry, Water

Pd/C as an efficient heterogeneous catalyst for carbonylative four-component synthesis of 4(3H)-quinazolinones

Pd/C as an efficient heterogeneous catalyst for carbonylative four-component synthesis of 4(3H)-quinazolinones

Catal. Sci. Technol., 2015, 5,4474-4480
DOI: 10.1039/C5CY00907C, Paper

Kishore Natte, Helfried Neumann, Xiao-Feng Wu

http://pubs.rsc.org/en/Content/ArticleLanding/2015/CY/C5CY00907C?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2Fcy+%28RSC+-+Catalysis+Science+%26+Technology+latest+articles%29#!divAbstract

http://www.rsc.org/suppdata/c5/cy/c5cy00907c/c5cy00907c1.pdf

A relatively mild, operationally simple, phosphine-free and recyclable catalytic system for the carbonylative synthesis of 4(3H)-quinazolinones with 2-iodoanilines, trimethyl orthoformate, and amines as the substrates has been developed.

Quinazolinones are of interest in the fields of pharmaceuticals and medicinal chemistry. 

The application of palladium on activated charcoal (Pd/C) as a heterogeneous catalyst was 

investigated for the carbonylation of 2-iodoanilines with trimethyl orthoformate and amines 

via a multicomponent reaction approach, which provided excellent yields of 4(3H)-quinazolinones. 

It avoids the use of expensive phosphine ligands with an additional advantage of catalyst recovery. 

Furthermore, >5 new quinazolinone scaffolds containing the trifluoroethyl group were introduced

 by this procedure; gram scale experiments were successfully performed as well.

General Procedure for the Synthesis of Quinazolinone: A 12 mL vial was charged with 10% Pd/C (1 mol%; 10 mg), 2-iodoaniline (1 mmol) and a stirring bar. Then, aniline (1.1 mmol), trimethyl orthoformate (2 mmol), DiPEA (3 mmol), and toluene (3 mL) were injected by syringe under argon. The vial (or several vials) was placed in an alloy plate, which was transferred into a 300 mL autoclave of the 4560 series from Parr Instruments® under argon atmosphere. After flushing the autoclave three times with CO, a pressure of 10 bar CO was adjusted at ambient temperature. Then, the reaction was performed for 20 h at 110 oC. After the reaction finished, the autoclave was cooled down to room temperature and the pressure was released carefully. The solution was filtered through whatmann filter paper and washed the reaction mixture with acetone (2-3 ml). After evaporation of the organic solvent the residue was adsorbed on silica gel and the crude product was purified by column chromatography using n-heptane/ethyl acetate (70:30) as eluent. 

Procedure for Catalyst Recycling The catalyst obtained after filtration was thoroughly washed with distilled water (3-5 mL) and then with methanol, acetone and ethyl acetate (3-5 mL) to remove any traces of organic material if present. The resulting catalyst was dried in an oven at 80 °C for 6 h and was then used for the next cycle. 

Pd/C as an efficient heterogeneous catalyst for carbonylative four-component synthesis of 4(3H)-quinazolinones

Kishore Natte,^a   Helfried Neumann^a and   Xiao-Feng Wu*^a  

*

Corresponding authors

^a

Leibniz-Institut für Katalyse an der Universität Rostock, Albert-Einstein-Straße 29a, 18059 Rostock, Germany
E-mail: xiao-feng.wu@catalysis.de

Catal. Sci. Technol., 2015,5, 4474-4480

DOI: 10.1039/C5CY00907C

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