Center for Molecular Modeling - GOA2010 B/10795/*

Use of 3-Hydroxy-4-(trifluoromethyl)azetidin-2-ones as Building Blocks for the Preparation of Trifluoromethyl-Containing Aminopropanes, 1,3-Oxazinan-2-ones, Aziridines, and 1,4-Dioxan-2-ones

wim — Wed, 20 Dec 2017 12:51:45 +0000

H.D. Thi, G. Le Nhat Thuy, S. Catak, V. Van Speybroeck, T. Van Nguyen, M. D'Hooghe

Synthesis-Stuttgart

50, 1439-1456

2018

Abstract

3-Hydroxy- 4-(trifluoromethyl)azetidin- 2-ones were efficiently synthesized from the corresponding 3-benzyloxy-β-lactams and successfully transformed into 3-chloro- 4-(trifluoromethyl)azetidin-2- one building blocks. The latter chlorides were shown to be eligible precursors for the construction of novel CF 3 -containing aminopropanes, 1,3-oxazinanes, 1,3-oxazinan-2- ones and aziridines. In addition, 3-hydroxy- 4-(trifluoromethyl)azetidin- 2-ones proved to be interesting substrates for the synthesis of novel 3-[2,2,2- trifluoro-1-(arylamino)ethyl]-1,4- dioxan-2- ones via intramolecular cyclization of 3-(2- hydroxyethoxy)-β-lactam intermediates.

DOI

http://dx.doi.org/10.1055/s-0036-1591537

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Synthesis (2018) 1439-1456.pdf

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

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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

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Piens_et_al-2017-Chemistry_-_A_European_Journal.pdf

Asymmetric synthesis of 3,4-disubstituted 2-(trifluoromethyl)pyrrolidines through rearrangement of chiral 2-(2,2,2-trifluoro-1-hydroxyethyl)azetidines

wim — Mon, 22 May 2017 06:36:21 +0000

J. Dolfen, E. Birsen Boydas, V. Van Speybroeck, S. Catak, K. Van Hecke, M. D'Hooghe

Journal of Organic Chemistry

82 (19), 10092–10109

2017

Abstract

Enantiopure 4-formyl-β-lactams were deployed as synthons for the diastereoselective formation of chiral 2-(2,2,2-trifluoro-1-hydroxyethyl)azetidines via trifluoromethylation through aldehyde modification followed by reductive removal of the β-lactam carbonyl moiety. Subsequent treatment of the (in situ) activated 2-trifluoroethylated azetidines with a variety of nitrogen, oxygen, sulfur and fluorine nucleophiles afforded chiral 3,4-disubstituted 2-(trifluoromethyl)pyrrolidines in good to excellent yields (45-99%) and high diastereoselectivities (dr > 99/1, 1H NMR) via interception of bicyclic aziridinium intermediates. Furthermore, representative pyrrolidines were N,O-debenzylated in a selective way and used for further synthetic elaboration to produce e.g. a CF3-substituted 2-oxa-4,7-diazabicyclo[3.3.0]octan-3-one system.

DOI

http://dx.doi.org/10.1021/acs.joc.7b01241

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acs.joc_.7b01241.pdf

Tandem addition of phosphite nucleophiles across unsaturated nitrogen-containing systems: mechanistic insights on regioselectivity

wim — Wed, 03 Aug 2016 06:19:18 +0000

W. Debrouwer, D. Hertsen, T.S.A Heugebaert, E. Birsen Boydas, V. Van Speybroeck, S. Catak, C.V. Stevens

Journal of Organic Chemistry

82 (1), 188–201

2017

Abstract

The addition of phosphite nucleophiles across linear unsaturated imines is a powerful and atom-economical methodology for the synthesis of aminophosphonates. These products are of interest from both a biological and a synthetic point of view: they act as amino acid transition state analogs and Horner–Wadsworth–Emmons reagents, respectively. In this work the reaction between dialkyl trimethylsilyl phosphites and α,β,γ,δ-diunsaturated imines was evaluated as a continuation of our previous efforts in the field. As such, the first conjugate 1,6-addition of a phosphite nucleophile across a linear unsaturated N-containing system is reported herein. Theoretical calculations were performed to rationalize the observed regioselectivites and to shed light on the proposed mechanism.

DOI

http://dx.doi.org/10.1021/acs.joc.6b02340

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acs%2Ejoc%2E6b02340.pdf

Heterogeneous Ru(III) oxidation catalysts via ‘click’ bidentate ligands on a Periodic Mesoporous Organosilica support

kevin — Tue, 31 May 2016 13:55:31 +0000

S. Clerick, E. De Canck, K. Hendrickx, V. Van Speybroeck, P. Van der Voort

Green Chemistry

18, 6035–6045

2016

Abstract

A 100% monoallyl ring-type Periodic Mesoporous Organosilica (PMO) is prepared as a novel, versatile and exceptionally stable catalytic support with a high internal surface area and 5.0 nm pores. Thiol-ene ‘click’ chemistry allows straightforward attachment of bifunctional thiols (-NH2, -OH, -SH) which, exploiting the thioether functionality formed, give rise to ‘solid’ bidentate ligands. [Ru(acac)2(CH3CN)2]PF6 is attached and complex formation on the solid is studied via theoretical calculations. All resulting solid catalysts show high activity and selectivity in alcohol oxidation reactions performed in green conditions (25°C/ water). The PMO catalysts do not leach Ru during reaction and are thus easily recuperated and re-used for several runs. Furthermore, oxidation of poorly water-soluble (±)-menthol illustrates the benefits of using hydrophobic PMOs as catalytic supports.

DOI

http://dx.doi.org/10.1039/C6GC01494A

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2016 - Clerick - GreenChem - 18 - 6035-6045.pdf

Facile synthesis of cooperative acid-base catalysts by clicking cysteine and cysteamine on an ethylene-bridged periodic mesoporous organosilica

kevin — Thu, 15 Oct 2015 15:13:43 +0000

J. Ouwehand, J. Lauwaert, D. Esquivel, K. Hendrickx, V. Van Speybroeck, J.W. Thybaut, P. Van der Voort

European Journal of Inorganic Chemistry

2016, 13-14, 2144-2151

2016

Abstract

A Periodic Mesoporous Organosilica (PMO) containing ethylene bridges was functionalized in order to obtain a series of cooperative acid-base catalysts. A straightforward, single-step procedure was devised to immobilize cysteine and cysteamine on the support material via a photoinitiated thiol-ene click reaction. Likewise, PMO materials capped with hexamethyldisilazane (HMDS) were used to support both compounds. This resulted in different materials, where the amine site was promoted by carboxylic acid groups, surface silanol groups or both. The catalysts were tested in the aldol reaction of 4-nitrobenzaldehyde and acetone. It was found that silanol groups have a stronger promoting effect on the amine than the carboxylic acid group. The highest turnover frequency (TOF) was obtained for an amine functionalized material which only contained silanol promoting sites. The loading of the active sites also has a significant effect on the activity of the catalysts, which was rationalized based on a computational study.

DOI

http://dx.doi.org/10.1002/ejic.201501179

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16-Eur-J-Inorg-Chem-xx(x)-Ouwehand.pdf

Systematic study of the chemical and hydrothermal stability of selected "stable" Metal Organic Frameworks

kevin — Thu, 24 Sep 2015 15:25:30 +0000

K. Leus, T. Bogaerts, J. De Decker, H. Depauw, K. Hendrickx, H. Vrielinck, V. Van Speybroeck, P. Van der Voort

Microporous and Mesoporous Materials

226, 110-116

2016

Abstract

In this work, the hydrothermal and chemical stability towards acids, bases, air, water and peroxides of Metal Organic Frameworks, that are commonly considered to be stable, is presented. As a proof of stability both the crystallinity and porosity are measured before and after exposure to the stress test. The major part of the MOFs examined in this study showed a good hydrothermal stability except for the UiO-67, NH2-MIL-101 (Al) and CuBTC material. The chemical stability towards acids and bases show a similar tendency and an ordering can be proposed as: MIL-101(Cr)>NH2-UiO-66>UiO-66>UiO-67>NH2-MIL-53>MIL-53(Al)>ZIF-8>CuBTC>NH2-MIL-101(Al). In the tests with the H2O2 solution most materials behaved poorly, only the UiO-66 and NH2-UiO-66 framework showed a good stability.

DOI

http://dx.doi.org/10.1016/j.micromeso.2015.11.055

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2016 - Leus - MMM - 226 - 110-116.pdf

Fine-tuning the theoretically predicted structure of MIL-47(V) with the aid of powder X-ray diffraction

michel — Wed, 15 Jul 2015 08:58:36 +0000

T. Bogaerts, L. Vanduyfhuys, D.E.P. Vanpoucke, J. Wieme, M. Waroquier, P. Van der Voort, V. Van Speybroeck

CrystEngComm

17, 8612–8622

2015

Abstract

The structural characterization of complex crystalline materials such as metal organic frameworks can prove a very difficult challenge both for experimentalists as for theoreticians. From theory, the flat potential energy surface of these highly flexible structures often leads to different geometries that are energetically very close to each other. In this work a distinction between various computationally determined structures is made by comparing experimental and theoretically derived X-ray diffractograms which are produced from the materials geometry. The presented approach allows to choose the most appropriate geometry of a MIL-47(V) MOF and even distinguish between different electronic configurations that induce small structural changes. Moreover the techniques presented here are used to verify the applicability of a newly developed force field for this material. The discussed methodology is of significant importance for modelling studies where accurate geometries are crucial, such as mechanical properties and adsorption of guest molecules.

DOI

http://dx.doi.org/10.1039/C5CE01388G

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authorreprints.pdf

The enantioselectivity of the manganese-salen complex in the epoxidation of unfunctionalized olefins and the influence of grafting

wim — Tue, 02 Jun 2015 07:02:43 +0000

T. Bogaerts, S. Wouters, P. Van der Voort, V. Van Speybroeck

Journal of Molecular Catalysis A: Chemical

Vol. 406, 106-113

2015

Abstract

Jacobsen’s complexes are famous for their usability for enantioselective epoxidations. However, the applicability of this catalytic system has been severely limited by several practical problems such as deactivation and separation after reaction. Grafting of Jacobsen-type complexes on solid supports is an attractive way to overcome these problems but led to a decrease in selectivity. A combined theoretical and experimental approach is presented to unravel the factors governing enantioselectivity. The importance of different substituents was determined by analyzing the transition state for the oxygen transfer using the full system as a model. An analysis of the asymmetric complex has shown an inherent tendency for a decreased selectivity due to the lack of specific bulky groups. Experimentally an immobilized Jacobsen catalyst on a metal organic framework (MIL-101) was synthesized which confirms the computational tendencies but the decrease in selectivity is limited, indicating that the MIL-101(Cr) is a suitable carrier for this complex.

Open Access version available at UGent repository

DOI

10.1016/j.molcata.2015.05.020

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15_j_mol_cat_a_chem_xxxxx_Bogaerts_manuscript.pdf

15_j_mol_cat_a_chem_xxxxx_Bogaerts.pdf