Projects per year
Abstract
Chemistry is fundamental in our society and plays a key role in every aspect of our lives, from our basic needs of food and clothing to life-saving medicine. The essence of organic chemistry and the synthesis of organic molecules like pharmaceuticals lies in the coupling of carbon atoms. The development of metal-catalyzed carbon-carbon bond forming cross-coupling reactions have been an immense advancement within chemistry invaluable for the pharmaceutical industry and society. This was acknowledged in 2010 where the Nobel Prize in chemistry was awarded for the work on cross-coupling reactions. Upgrading existing carbon-carbon bond forming protocols and developing new methodologies are an imperative endeavor for the chemical industry and for the betterment of mankind. This thesis contains three projects. The first project aims at improving an existing catalytic C-C bond forming system by making the catalyst reusable and suitable for continuous flow setups. The last two projects are focused on developing novel C-C forging methodologies via direct C-H functionalization.
In the first project, a chiral nickel(II) bis(diamine) complex was incorporated into a polystyrene matrix without compromising the catalytic properties of the nickel compex. The catalyst effectively catalyzed the asymmetric Michael addition of malonates to nitroalkenes and was easily reused. The catalyst showed good tolerance towards sensitive functional groups, was suitable for a continuous flow setup and obtained a TON almost five times higher than previous reports. To illustrate the relevance of the catalytic system, the protocol was used to synthesize the blockbuster drug Pregabalin in 88% overall yield.
In the second project, a novel methodology for the alkynylation of benzylic C-H bonds was developed. Using copper catalysis in combination with NFSI it was possible to develop a coupling protocol between alkynyl boronic esters and 1-alkyl naphthalenes, with the C-H substrate as the limiting reagent. The protocol showed a good functional group tolerance, however, the C-H source was limited to 1-alkyl napthalenes. Preliminary mechanistic experiments in combinations with literature points towards a mechanism resembling a radical relay process.
In the third project, a novel methodology for the direct alkylation of allylic C-H bonds was developed. Using a combination of a nickel catalyst and a photocatalyst a protocol for the coupling of alkyl bromides with terminal olefins was developed. The methodology proceeds at benign conditions and exclusively yields the linear product. The protocol is robust towards functional groups and even densely functionalized biological derivatives could be utilized. A preliminary mechanistic investigation indicated that the photocatalyst function as a SET species which catalytic cycle is intertwined with the catalytic cycle of nickel.
In the first project, a chiral nickel(II) bis(diamine) complex was incorporated into a polystyrene matrix without compromising the catalytic properties of the nickel compex. The catalyst effectively catalyzed the asymmetric Michael addition of malonates to nitroalkenes and was easily reused. The catalyst showed good tolerance towards sensitive functional groups, was suitable for a continuous flow setup and obtained a TON almost five times higher than previous reports. To illustrate the relevance of the catalytic system, the protocol was used to synthesize the blockbuster drug Pregabalin in 88% overall yield.
In the second project, a novel methodology for the alkynylation of benzylic C-H bonds was developed. Using copper catalysis in combination with NFSI it was possible to develop a coupling protocol between alkynyl boronic esters and 1-alkyl naphthalenes, with the C-H substrate as the limiting reagent. The protocol showed a good functional group tolerance, however, the C-H source was limited to 1-alkyl napthalenes. Preliminary mechanistic experiments in combinations with literature points towards a mechanism resembling a radical relay process.
In the third project, a novel methodology for the direct alkylation of allylic C-H bonds was developed. Using a combination of a nickel catalyst and a photocatalyst a protocol for the coupling of alkyl bromides with terminal olefins was developed. The methodology proceeds at benign conditions and exclusively yields the linear product. The protocol is robust towards functional groups and even densely functionalized biological derivatives could be utilized. A preliminary mechanistic investigation indicated that the photocatalyst function as a SET species which catalytic cycle is intertwined with the catalytic cycle of nickel.
Original language | English |
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Publisher | DTU Chemistry |
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Number of pages | 118 |
Publication status | Published - 2021 |
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Dive into the research topics of 'First-Row Transition Metal-Catalyzed Carbon-Carbon Bond Formation'. Together they form a unique fingerprint.Projects
- 1 Finished
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Design of single-site porous organic polymer catalysts for C-H functionalization
Buendia, M. B. (PhD Student), Tanner, D. A. (Examiner), Jessing, M. (Examiner), Kegnæs, S. (Main Supervisor), Kramer, S. (Supervisor) & Mazet, C. (Examiner)
Technical University of Denmark
15/08/2018 → 08/11/2021
Project: PhD