Cross coupling reactions are a well-established tool in modern organic synthesis and
play a crucial role in the synthesis of a high number of organic compounds. Their
importance is highlighted by the Nobel Prize in chemistry to Suzuki, Heck and Negishi in
2010. The increasing importance of sustainability requirements in chemical production
has furthermore promoted the development of cross-coupling protocols that comply
with the principles of “Green Chemistry”1. The Sonogashira reaction is today the most
versatile and powerful way to generate aryl alkynes, a moiety recurring in many
pharmaceutical and natural products. Despite many improvements to the original
reaction, reports on generally applicable protocols that work under sustainable
conditions are scarce. Our group recently reported an efficient protocol for a copperfree
Sonogashira cross-coupling at low temperature, in aqueous medium and with no
addition of organic solvents or additives2.
The goal of this work was to further investigate the effects of different reaction
parameters on the catalytic activity in order to optimize the protocol. Limitations of the protocol were tested in respect to reaction temperature, heating method, atmosphere,
base type and amount, catalyst loading, reaction time and work up procedure.
The reaction worked successfully under air and results were not affected by the
presence of oxygen in the water phase. Among a variety of bases tested, triethylamine
was confirmed to give the best results and its required excess could be reduced from
nine to four equivalents. Catalyst loading could also be reduced by up to 90%: Good to
near quantitative yields for a broad range of substrates were achieved using a catalyst
concentration of 0.25mol% and 5 eq of Et3N at 50°C while more reactive substrates
could be coupled with a catalyst concentration as low as 0.025mol%. Filtration
experiments showed the possibility of a simplified work up procedure and a protocol
completely free of organic solvents.
This optimized protocol can be applied to a broad range of substrates, delivers high
yields, avoids formation of toxic byproducts, works under air and aqueous conditions,
allows for simple product isolation and thus meets not only the criteria of “Green
Chemistry” but also those of “Click-Chemistry”
| Identifer | oai:union.ndltd.org:kaust.edu.sa/oai:repository.kaust.edu.sa:10754/262732 |
| Date | 12 1900 |
| Creators | Walter, Philipp E. |
| Contributors | Eppinger, Jörg, Physical Science and Engineering (PSE) Division, Huang, Kuo-Wei, Takanabe, Kazuhiro |
| Source Sets | King Abdullah University of Science and Technology |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Rights | 2015-01-01, At the time of archiving, the student author of this thesis opted to temporarily restrict access to it. The full text of this thesis became available to the public after the expiration of the embargo on 2015-01-01. |
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