Focus

The main focus of the organic synthesis research group is the chemical synthesis and derivatisation of organic compounds with non-trivial carbon connectivities, such as those found in polycyclic Natural Products. The design and selection of target structures is guided by a specific interest in reactivity patterns and/or a specific interest in biological phenomena. This research often follows a substrate-driven approach which relies on the use of highly modular synthetic intermediates as versatile building blocks or chemical platforms for various applications.

  • The chemical synthesis research mainly involves the development of novel strategies and methods to assemble complex polycyclic scaffolds found in Nature, focusing on multiple bond forming steps such as cycloadditions and cascade reactions. [1], [2]
  • The chemical derivatisation research focuses on the development of application-oriented versatile covalent ligation reactions (such as click-type reactions) to generate multiple functional derivatives from simple substrates or synthetic intermediates. [3]
  • A major recent theme, which encompasses both of the above general topics, consists of research directed at the design and synthesis of highly modular synthetic building blocks that allow a rapid exploration of Natural Product-like chemical space using simple and orthogonal functional group transformations. [4]
  • The concepts of versatile ligation/functionalisation reactions and modular building blocks in organic synthesis are also explored and applied in various collaborative research projects ranging from macromolecular and materials science to chemical biology. [5], [6]

publications

Publications

Doing both independent work and collaborations.

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courses

Courses

Giving courses to BSc and MSc in chemistry

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people

People

Former and current people working in the group.

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contact

Contact

For questions, do not hesitate to contact us.

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Latest publications

The latest independent publications are given below, for all independent publications and collaborations, see publications

Phenylpropynones as Selective Disulfide Rebridging Bioconjugation Reagents

Phenylpropynones as Selective Disulfide Rebridging Bioconjugation Reagents

Simple 1-phenylpropynones undergo a selective double thia-Michael addition with thiols in buffered media, yielding an interesting dithioacetal linkage joining two thiols. The reactivity of various Michael-alkyne reagents is compared in this chemoselective, atom economical, and non-oxidative cross-linking of two thiols. The stability and chemical reactivity of the dithioacetal links are studied, and the utility of the disulfide targeting bioconjugation methodology is shown by the selective rebridging of native cyclic peptides after the reductive cleavage of their disulfide bridge.

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Site selective Gold(I)-Catalysed Benzylic C-H Amination via an Intermolecular Hydride Transfer to Triazolinediones

Site selective Gold(I)-Catalysed Benzylic C-H Amination via an Intermolecular Hydride Transfer to Triazolinediones

Triazolinediones are known as highly reactive dienophiles that can also act as electrophilic amination reagents towards enolisable C-H bonds (ionic pathway) or weak C-H bonds (free radical pathway). Here, we report that this C-H amination reactivity can be significantly extended and enhanced via gold(I)-catalysis. Under mild conditions, several alkyl-substituted aryls successfully undergo benzylic C-H aminations at room temperature. The remarkable site selectivity that is observed points towards strong electronic activation and deactivation effects, that go beyond a simple weakening of the C-H bond. The observed catalytic C-H aminations do not follow the expected trends for a free radical-type C-H amination and show complementarity to existing methods. Density functional theory (DFT) calculations and distinct experimental trends provide a clear mechanistic rationale for observed selectivity patterns, postulating a novel pathway for tria-zolinedione-induced aminations via a carbon-to-nitrogen hydride transfer.

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Dithioallyl cation (3 + 2) cycloadditions under aprotic reaction conditions: rapid access to spiro-fused cyclopentane scaffolds

Dithioallyl cation (3 + 2) cycloadditions under aprotic reaction conditions: rapid access to spiro-fused cyclopentane scaffolds

We report a general method to effect all-carbon (3 + 2) cycloadditions that can elaborate cyclopentenes from a range of olefins. The required dithioallyl cation reagents can be generated in a newly developed mild protocol starting from 2-allyloxypyridine precursors, thus avoiding the use of strong Brønsted acids. The novel method significantly expands the substrate scope, which now also includes acid-sensitive olefins, and thus enables the preparation of previously inaccessible spiro-fused scaffold types from simple and readily available starting materials.

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Dithioallyl Cations in Stereoselective Dearomative (3 + 2) Cycloadditions of Benzofurans: Mechanism and Synthetic Applications

Dithioallyl Cations in Stereoselective Dearomative (3 + 2) Cycloadditions of Benzofurans: Mechanism and Synthetic Applications

A stereoselective dearomative cyclopentannulation of benzofurans is reported. A previously reported dearomative (3 + 2) cycloaddition of indoles with 1,4-dithiane-fused allyl cations was found to lack stereoselectivity when more substituted cyclopentene rings are targeted. However, for benzofuran substrates, excellent levels of stereoselectivity were observed for the same allyl cation reagents under very similar reaction conditions. In this full account, we provide a mechanistic rationale and some design principles that govern the stereoselectivity of the intriguing dearomative transformations using dithioallyl cations and demonstrate how the stereoselectivity depends on electronic factors of the starting materials. The stereoselective methodology is also applied in a straightforward dearomative synthesis of the tricyclic sesquiterpenoid natural product aplysin and its analogues, starting from a simple benzofuran.

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La Chimie crée son objet. Cette faculté créatrice, semblable a l’art lui-même, la distingue essentiellement de sciences naturelles et historiques.

Marcelin Berthelot, 1876