Center for Molecular Modeling - H. Goossens

Formation of Fluorinated Amido Esters through Unexpected C3-C4 Bond Fission in 4-Trifluoromethyl-3-oxo-β-lactams

wim — Wed, 22 Nov 2017 14:46:09 +0000

H.D. Thi, H. Goossens, D. Hertsen, V. Otte, T. Van Nguyen, V. Van Speybroeck, M. D'Hooghe

Chemistry - An Asian Journal

13 (4), 421-431

2018

Abstract

4-Trifluoromethyl-3-oxo-β-lactams were unexpectedly transformed into 2-[(2,2-difluorovinyl)amino]-2-oxoacetates as major products, accompanied by minor amounts of 2-oxo-2-[(2,2,2-trifluoroethyl)amino]acetates, upon treatment with alkyl halides and triethylamine in DMSO. This peculiar C3-C4 bond fission reactivity was investigated in-depth, from both an experimental and a computational point of view, in order to shed light on the underlying reaction mechanism.

DOI

http://dx.doi.org/10.1002/asia.201701636

Private attachment

Chemistry - An Asian Journal (2018) 421-431.pdf

Reactivity of 3-oxo-β-lactams with respect to primary amines - an experimental and computational approach

wim — Wed, 16 Aug 2017 12:50:14 +0000

N. Piens, H. Goossens, D. Hertsen, S. Deketelaere, L. Crul, L. Demeurisse, J. De Moor, E. Van den Broeck, K. Mollet, K. Van Hecke, V. Van Speybroeck, M. D'Hooghe

Chemistry - A European Journal

2017 (23), 1-9

2017

Abstract

The reactivity of 3-oxo-β-lactams with respect to primary amines was investigated in depth. Depending on the specific azetidin-2-one C4 substituent, this reaction was shown to selectively produce 3-imino-β-lactams (through dehydration), α-aminoamides (through CO elimination) or ethanediamides (through an unprecedented C3-C4 ring opening). In addition to the experimental results, the mechanisms and factors governing these peculiar transformations were also examined and elucidated by means of density functional theory calculations.

DOI

http://dx.doi.org/10.1002/chem.201703852

Private attachment

Piens_et_al-2017-Chemistry_-_A_European_Journal.pdf

Design of a thermally controlled sequence of triazolinedione-based click and transclick reactions

wim — Mon, 27 Mar 2017 07:43:57 +0000

H.A. Houck, K. De Bruycker, S. Billiet, B. Dhanis, H. Goossens, S. Catak, V. Van Speybroeck, J.M. Winne, F. Du Prez

Chemical Science

8 (4), 3098-3108

2017

Abstract

The reaction of triazolinediones (TADs) and indoles is of particular interest for polymer chemistry applications, as it is a very fast and irreversible additive-free process at room temperature, but can be turned into a dynamic covalent bond forming process at elevated temperatures, giving a reliable bond exchange or ‘transclick’ reaction. In this paper, we report an in-depth study aimed at controlling the TAD – indole reversible click reactions through rational design of modified indole reaction partners. This has resulted in the identification of a novel class of easily accessible indole derivatives that give dynamic TAD-adduct formation at significantly lower temperatures. We further demonstrate that these new substrates can be used to design a directed cascade of click reactions of a functionalized TAD moiety from an initial indole reaction partner to a second indole, and finally to an irreversible reaction partner. This controlled sequence of click and transclick reactions of a single TAD reagent between three different substrates has been demonstrated both on small molecule and macromolecular level, and the factors that control the reversibility profiles have been rationalized and guided by mechanistic considerations supported by theoretical calculations.

Open Access version available at UGent repository

Green Open Access

DOI

http://dx.doi.org/10.1039/c7sc00119c

Private attachment

Hannes2017.pdf

Effect of Lewis acids on the stereoregularity of N,N-dimethyl acrylamide: A computational approach

michel — Sat, 09 Jul 2016 19:13:11 +0000

T. Furuncuoğlu, B. Kura, S. Catak, H. Goossens, V. Van Speybroeck, M. Waroquier, V. Aviyente

European Polymer Journal

83, 67–76

2016

Abstract

In this study, the effect of Lewis acid coordination (ScCl3) in controlling the stereoregularity during the free radical polymerization of N,N-dimethyl acrylamide (DMAM) has been investigated by Density Functional Theory (DFT). Experimentally, ScCl3, Sc(OTf)3 and Yb(OTf)3 have been used to increase the isotactic percentage in the polymerization of another acrylamide derivative, N-isopropyl acrylamide (NIPAM) (Habaue et al., 2002). The relative orientation of the terminal and penultimate side chains is expected to determine the stereoregularity in free radical polymerization reactions (Noble et al., 2014). We have analyzed the mechanistic details of the propagation reaction by considering all coordination types of the Lewis acid to the propagating species. Calculations have shown the bridging of the Lewis acid between the terminal side chain and the monomer to be the most probable pathway, which is in favor of the pro-meso propagation during the free radical polymerization of DMAM. In this case, it is the bridging capacity of the catalyst along the less crowded direction that dictates the preference for isotacticity. Overall, the strategy suggested in this study can be easily used by experimentalists in their endeavour of choosing the catalysts in order to end-up with the desired stereoregulation of the polymer chain.

DOI

http://dx.doi.org/10.1016/j.eurpolymj.2016.08.010

Private attachment

1-s2.0-S0014305716306024-main.pdf

Beyond the diketopiperazine family with alternatively bridged brevianamide F analogues

michel — Mon, 23 Mar 2015 09:21:11 +0000

I. Wauters, H. Goossens, E. Delbeke, K. Muylaert, B.I. Roman, K. Van Hecke, V. Van Speybroeck, C.V. Stevens

Chemistry - A European Journal

80 (16), 8046-8054

2015

Abstract

A method for the preparation of 3,5-bridged piperazin-2-ones from a tryptophan–proline-based diketopiperazine is described using diphosgene to induce the ring closure. Density functional theory calculations were conducted to study the mechanism of this C–C bond formation. Several derivatives of the thus obtained α-chloroamine were synthesized by substitution of the chlorine atom using a range of O-, N-, S-, and C-nucleophiles. This novel class of brevianamide F analogues possess interesting breast cancer resistance protein inhibitory activity.

DOI

http://dx.doi.org/10.1021/acs.joc.5b01161

Private attachment

15-ChemEurJ-80(16)8046-Wauters.pdf

On the Possibility of [1,5] Sigmatropic Shifts in Bicyclo[4.2.0]octa-2,4-dienes

michel — Sun, 30 Nov 2014 13:27:40 +0000

H. Goossens, J.M. Winne, S. Wouters, L. Hermosilla, P. J. De Clercq, M. Waroquier, V. Van Speybroeck, S. Catak

Journal of Organic Chemistry

80 (5) 2609-2620

2015

Abstract

The thermal equilibration of the methyl esters of endiandric acids D and E was subject to a computational study. An electrocyclic pathway via an electrocyclic ring opening followed by a ring flip and a subsequent electrocyclization proposed by Nicolaou [Chem. Soc. Rev. 2009], was computationally explored. The free energy barrier for this electrocyclic route was shown to be very close to the bicyclo[4.2.0]octa-2,4-diene reported by Huisgen [Tet. Lett. 1968]. Furthermore, the possibility of a [1,5] sigmatropic alkyl group shift of bicyclo[4.2.0]octa-2,4-diene systems at high temperatures was explored in a combined computational and experimental study. Calculated reaction barriers for a biradical-mediated stepwise [1,5] sigmatropic alkyl group shift were shown to be comparable with the reaction barriers for the bicyclo[4.1.0]hepta-2,4-diene (norcaradiene) walk rearrangement, whereas calculated reaction barriers for a concerted [1,5] sigmatropic alkyl group shift were found to be higher in energy. However, the stepwise pathway is suggested to only be feasible for appropriately substituted compounds. Experiments conducted on a deuterated analogous diol derivative confirmed the calculated (large) differences in barriers between electrocyclic and sigmatropic pathways.

DOI

http://dx.doi.org/10.1021/jo5027639

Private attachment

15_JOC_xxxx_HGoossens.pdf

Elucidating the Structural Isomerism of Fluorescent Strigolactone Analogue CISA-1

lore — Tue, 25 Nov 2014 13:44:51 +0000

H. Goossens, T.S.A Heugebaert, B. Dereli, M. Van Overtveldt, O. Karahan, I. Doğan, M. Waroquier, V. Van Speybroeck, V. Aviyente, S. Catak, C.V. Stevens

European Journal of Organic Chemistry

2015 (6), 1211–1217

2015

Abstract

The synthesis of a new potent strigolactone analogue (CISA-1), resulting in the formation of two interconverting structural isomers, which could not be identified, was recently reported by Rasmussen et al [Molecular Plant, 2013, 6, 100]. In the present study, a combined computational and experimental approach is used to identify the exact nature of these structural isomers. While standard experimental techniques were not able to determine the identity of the isomers, chromatographic methods excluded E/Z isomerisation. Computational 1H NMR chemical shift values and DFT calculations on interconversion barriers strongly suggest that the CISA-1 isomers were interconverting (Z)-configured atropisomers.

DOI

http://dx.doi.org/10.1002/ejoc.201403457

Private attachment

15_EurJOC_xxxx_HGoossens.pdf

15_EurJOC_2015(6)_1211_HGoossens.pdf

Accelerated living cationic ring-opening polymerization of a methyl ester functionalized 2-oxazoline monomer

dietmar — Wed, 19 Nov 2014 15:41:28 +0000

P.J.M. Bouten, D. Hertsen, M. Vergaelen, B. Monnery, M.A. Boerman, H. Goossens, S. Catak, J.C.M. van Hest, V. Van Speybroeck, R. Hoogenboom

Polymer Chemistry

6, 514-518

2015

Abstract

Kinetic studies on the homo- and copolymerization of 2-methoxycarboxyethyl-2-oxazoline (MestOx) with 2-methyl-2-oxazoline (MeOx) and 2-ethyl-2-oxazoline (EtOx) were performed. For the homopolymerisation of MestOx an increased propagation rate constant was observed compared to MeOx and EtOx while the copolymerization of MestOx with MeOx or EtOx unexpectedly revealed slower incorporation of MestOx. Density functional theory (DFT) calculations show that nearby MestOx residues in the living chain can activate both the oxazolinium chain end and the attacking monomer, stabilizing the propagation transition state, leading to faster homopolymerisation of MestOx. These effects also accelerate incorporation of both monomers in the copolymerisations. However, since MeOx is shown to be more nucleophilic than MestOx, the incorporation order is reversed in the copolymerisations.

Open Access version available at UGent repository

DOI

http://dx.doi.org/10.1039/C4PY01373E

Private attachment

14_Polym-Chem_2015_6_514_Bouten.pdf

Triazolinediones enabling ultrafast and reversible click chemistry for facile design of healable and reshapable polymers

michel — Fri, 27 Jun 2014 13:56:44 +0000

S. Billiet, K. De Bruycker, F. Driessen, H. Goossens, V. Van Speybroeck, J. Winne, F. Du Prez

Nature Chemistry

6 (9), 815-821

2014

Abstract

With its focus on synthetic reactions that are highly specific and reliable, ‘click’ chemistry has become a valuable tool for many scientific research areas and applications. Combining the modular, covalently bonded nature of click-chemistry linkages with an ability to reverse these linkages and reuse the constituent reactants in another click reaction, however, is a feature that is not found in most click reactions. Here we show that triazolinedione compounds can be used in click-chemistry applications. We present examples of simple and ultrafast macromolecular functionalization, polymer–polymer linking and polymer crosslinking under ambient conditions without the need for a catalyst. Moreover, when triazolinediones are combined with indole reaction partners, the reverse reaction can also be induced at elevated temperatures, and the triazolinedione reacted with a different reaction partner, reversibly or irreversibly dependent on its exact nature. We have used this ‘transclick’ reaction to introduce thermoreversible links into polyurethane and polymethacrylate materials, which allows dynamic polymer-network healing, reshaping and recycling.

DOI

http://dx.doi.org/10.1038/nchem.2023

Private attachment

14_NatureChemistry_6(9)815_Billiet.pdf

Nucleophile-Dependent Regio- and Stereoselective Ring Opening of 1-Azoniabicyclo-[3.1.0]hexane Tosylate

michel — Sat, 30 Nov 2013 15:23:21 +0000

Mi-Kyung Ji, D. Hertsen, D.-H. Yoon, H. Eum, H. Goossens, M. Waroquier, V. Van Speybroeck, M. D'Hooghe, N. De Kimpe, H.-J. Ha

Chemistry - An Asian Journal

2014 (9), 1060-1067

2014

Abstract

1-[(1R)-(1-Phenylethyl)]-1-azoniabicyclo[3.1.0]hexane tosylate was generated as a stable bicyclic aziridinium salt from the corresponding 2-(3-hydroxypropyl)aziridine upon reaction with p-toluenesulfonyl anhydride. This bicyclic aziridinium ion was then treated with various nucleophiles including halides, azide, acetate, and cyanide in CH3CN to afford either piperidines or pyrrolidines through regio- and stereoselective ring opening, mediated by the characteristics of the applied nucleophile. On the basis of DFT calculations, ring-opening reactions under thermodynamic control yield piperidines, whereas reactions under kinetic control can yield both piperidines and pyrrolidines depending on the activation energies for both pathways.

DOI

http://dx.doi.org/10.1002/asia.201301551

Private attachment

14_chemasianjournal_2014(9)1060_Ji.pdf