| 1. |
- Slagbrand, Tove, et al.
(författare)
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Bimetallic Catalysis : Asymmetric Transfer Hydrogenation of Sterically Hindered Ketones Catalyzed by Ruthenium and Potassium
- 2015
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Ingår i: ChemCatChem. - : WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. - 1867-3880 .- 1867-3899. ; 7:21, s. 3445-3449
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Tidskriftsartikel (refereegranskat)abstract
- An efficient protocol for the asymmetric reduction of sterically hindered ketones under transfer-hydrogenation conditions was developed. The corresponding chiral alcohols were obtained in good to excellent yields with enantiomeric excess values up to 99%. The role of the cation associated with the base present in the reduction reaction was investigated. In contrast to previous studies on this catalyst system, potassium ions rather than lithium ions significantly enhanced the reaction outcome.
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| 2. |
- Alm, Erik, 1980-, et al.
(författare)
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Automated annotation and quantification of metabolites in (1)H NMR data of biological origin
- 2012
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 403:2, s. 443-455
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Tidskriftsartikel (refereegranskat)abstract
- In 1H NMR metabolomic datasets, there are often over a thousand peaks per spectrum, many of which change position drastically between samples. Automatic alignment, annotation, and quantification of all the metabolites of interest in such datasets have not been feasible. In this work we propose a fully automated annotation and quantification procedure which requires annotation of metabolites only in a single spectrum. The reference database built from that single spectrum can be used for any number of 1H NMR datasets with a similar matrix. The procedure is based on the generalized fuzzy Hough transform (GFHT) for alignment and on Principal-components analysis (PCA) for peak selection and quantification. We show that we can establish quantities of 21 metabolites in several 1H NMR datasets and that the procedure is extendable to include any number of metabolites that can be identified in a single spectrum. The procedure speeds up the quantification of previously known metabolites and also returns a table containing the intensities and locations of all the peaks that were found and aligned but not assigned to a known metabolite. This enables both biopattern analysis of known metabolites and data mining for new potential biomarkers among the unknowns.
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| 3. |
- Margalef, Jessica, et al.
(författare)
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Third-Generation Amino Acid Furanoside-Based Ligands from d-Mannose for the Asymmetric Transfer Hydrogenation of Ketones : Catalysts with an Exceptionally Wide Substrate Scope
- 2016
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Ingår i: Advanced Synthesis and Catalysis. - : Wiley. - 1615-4150 .- 1615-4169. ; 358:24, s. 4006-4018
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Tidskriftsartikel (refereegranskat)abstract
- A modular ligand library of -amino acid hydroxyamides and thioamides was prepared from 10 different N-tert-butyloxycarbonyl-protected -amino acids and three different amino alcohols derived from 2,3-O-isopropylidene--d-mannofuranoside. The ligand library was evaluated in the half-sandwich ruthenium- and rhodium-catalyzed asymmetric transfer hydrogenation of a wide array of ketone substrates, including simple as well as sterically demanding aryl alkyl ketones, aryl fluoroalkyl ketones, heteroaromatic alkyl ketones, aliphatic, conjugated and propargylic ketones. Under the optimized reaction conditions, secondary alcohols were obtained in high yields and in enantioselectivities up to >99%. The choice of ligand/catalyst allowed for the generation of both enantiomers of the secondary alcohols, where the ruthenium-hydroxyamide and the rhodium-thioamide catalysts act complementarily towards each other. The catalytic systems were also evaluated in the tandem isomerization/asymmetric transfer hydrogenation of racemic allylic alcohols to yield enantiomerically enriched saturated secondary alcohols in up to 98% ee. Furthermore, the catalytic tandem -alkylation/asymmetric transfer hydrogenation of acetophenones and 3-acetylpyridine with primary alcohols as alkylating and reducing agents was studied. Secondary alcohols containing an elongated alkyl chain were obtained in up to 92% ee.
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| 4. |
- Slagbrand, Tove, et al.
(författare)
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An Efficient One-pot Procedure for the Direct Preparation of 4,5-Dihydroisoxazoles from Amides
- 2017
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Ingår i: Advanced Synthesis and Catalysis. - : Wiley. - 1615-4150 .- 1615-4169. ; 359:11, s. 1990-1995
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Tidskriftsartikel (refereegranskat)abstract
- A Mo(CO)(6) (molybdenumhexacarbonyl) catalyzed reductive functionalization of amides to afford 5-amino substituted 4,5-dihydroisoxazoles is presented. The reduction of amides generates reactive enamines, which upon the addition of hydroximinoyl chlorides and base undergoes a 1,3-dipolar cycloaddition reaction that gives access to the desired heterocyclic compounds. The transformation of amides is highly chemoselective and tolerates functional groups such as nitro, nitriles, esters, and ketones. Furthermore, a versatile scope of 4,5-dihydroisoxazoles derived from a variety of hydroximinoyl chlorides and amides is demonstrated.
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| 5. |
- Slagbrand, Tove, 1989-
(författare)
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Development and Applications of Molybdenum-Catalyzed Chemoselective Amide Reduction
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis covers the development of catalytic methodologies for the mild and chemoselective hydrosilylation of amides. The first part describes the investigation of the Mo(CO)6-catalyzed reduction of carboxamides. It was found that the reduction could be controlled by tuning the reaction temperature and either amines or aldehydes could be obtained selectively. The system showed an unprecedented chemoselectivity and the amide reduction could take place in the presence of other reducible functional groups such as ketones, aldehydes, and imines. Moreover, the transformation could be performed on a preparative scale and was further employed in the synthesis of Donepezil, a pharmaceutical drug used in the treatment of Alzheimer´s disease.The third chapter concerns the development of the Mo(CO)6-mediated hydrosilylation protocol for the reduction of carboxamides containing acidic α-hydrogens. In this case, enamines were formed and a high level of chemoselectivity was observed. Enamines containing sensitive functional groups such as ketones, aldehydes and imines were generated. The enamines were not isolated but used in subsequent catalytic reductive functionalization of amides, which is described in the last part of the thesis (Chapters 4 – 7). The in situ formed enamines were reacted with a wide variety of electrophiles, generating heterocyclic compounds as triazolines, triazoles, 4,5-dihydroisoxazoles and pyrimidinediones. N-sulfonylformamidines as well as thioacrylamides could also be prepared with this approach. The protocols for the synthesis of triazolines, triazoles and N-sulfonylformamidines could additionally be performed on a preparative scale, showing the practicality of the methodology.
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| 6. |
- Slagbrand, Tove
(författare)
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Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation
- 2015
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis covers the development of two new methods for the asymmetric reduction of ketones and ketone intermediates. The protocols developed are based on the use of a ruthenium pseudo-dipeptide catalyst that previously has been shown to be efficient and selective in the asymmetric reduction of carbonyl compounds.The first part of this thesis describes the development of an efficient protocol for sequential isomerization and asymmetric reduction of allylic alcohols into saturated chiral alcohols in a one-pot procedure. This transformation has previously been reported at high temperature and with long reaction times, yielding the products in poor enantioselectivity. In the current project, the same transformation was investigated, however, with a significally more active catalyst. As a result we were able to use milder reaction conditions which yielded higher enantioselectivity in comparison to previously published protocols. The scope was investigated and the mechanism was briefly studied.The second part of this thesis describes the asymmetric reduction of sterically demanding ketones with the same metal complex as in the first part. It was found that longer reaction times in combination with the use of potassium tert-butoxide facilitate the reduction of sterically hindered ketones, to yield secondary alcohols with high enantioselectivity. The scope and the role of potassium were investigated, and a plausible new transition state was postulated.
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| 7. |
- Slagbrand, Tove, et al.
(författare)
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Ruthenium-Catalyzed Tandem-Isomerization/Asymmetric Transfer Hydrogenation of Allylic Alcohols
- 2014
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 20:49, s. 16102-16106
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Tidskriftsartikel (refereegranskat)abstract
- A one-pot procedure for the direct conversion of racemic allylic alcohols to enantiomerically enriched saturated alcohols is presented. The tandem-isomerization/asymmetric transfer hydrogenation process is efficiently catalyzed by [{Ru(p-cymene)Cl-2}(2)] in combination with the -amino acid hydroxyamide ligand 1, and performed under mild conditions in a mixture of ethanol and THF. The saturated alcohol products are isolated in good to excellent chemical yields and in enantiomeric excess up to 93%.
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| 8. |
- Slagbrand, Tove, et al.
(författare)
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Transformation of Amides into Highly Functionalized Triazolines
- 2017
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Ingår i: ACS Catalysis. - : American Chemical Society (ACS). - 2155-5435. ; 7:3, s. 1771-1775
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Tidskriftsartikel (refereegranskat)abstract
- Triazoles and triazolines are important classes of heterocyclic compounds known to exhibit biological activity. Significant focus has been given to the development of synthetic approaches for the preparation of triazoles, and they are today easily obtainable through a large variety of protocols. The number of synthetic procedures for the formation of triazolines, on the other hand, is limited and further research in this field is required. The protocol presented here gives access to a broad scope of 1,4,5-substituted 1,2,3-triazolines through a one-pot transformation of carboxamides. The two-step procedure involves a Mo(CO)6-catalyzed reduction of tertiary amides to afford the corresponding enamines, followed by in situ cycloaddition of organic azides to form triazolines. The amide reduction is chemoselective and allows for a wide variety of functional groups such as esters, ketones, aldehydes, and imines to be tolerated. Furthermore, a modification of this one-pot procedure gives access to the corresponding triazoles. The chemically stable amide functionality is demonstrated to be an efficient synthetic handle for the formation of highly substituted triazolines or triazoles.
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| 9. |
- Tinnis, Fredrik, et al.
(författare)
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Chemoselective Reduction of Tertiary Amides under Thermal Control: Formation of either Aldehydes or Amines
- 2016
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 55:14, s. 4562-4566
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Tidskriftsartikel (refereegranskat)abstract
- The chemoselective reduction of amides in the presence of other more reactive reducible functional groups is a highly challenging transformation, and successful examples thereof are most valuable in synthetic organic chemistry. Only a limited number of systems have demonstrated the chemoselective reduction of amides over ketones. Until now, the aldehyde functionality has not been shown to be compatible in any catalytic reduction protocol. Described herein is a [Mo(CO)6]-catalyzed protocol with an unprecedented chemoselectivity and allows for the reduction of amides in the presence of aldehydes and imines. Furthermore, the system proved to be tunable by variation of the temperature, which enabled for either C−O or C−N bond cleavage that ultimately led to the isolation of both amines and aldehydes, respectively, in high chemical yields.
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| 10. |
- Trillo, Paz, et al.
(författare)
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Facile preparation of pyrimidinediones and thioacrylamides via reductive functionalization of amides
- 2017
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Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1359-7345 .- 1364-548X. ; 53:65, s. 9159-9162
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Tidskriftsartikel (refereegranskat)abstract
- The development of an efficient protocol for the reductive functionalization of amides into pyrimidinediones and amino-substituted thioacrylamides is presented. Enamines are generated in a highly chemoselective amide hydrosilylation reaction catalyzed by molybdenum hexacarbonyl in combination with 1,1,3,3-tetramethyldisiloxane. The direct addition of either isocyanate or isothiocyanate generates the corresponding pyrimidinediones and 3-aminothioacrylamides in high yields.
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| 11. |
- Trillo, Paz, et al.
(författare)
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Mild Reductive Functionalization of Amides into N-Sulfonylformamidines
- 2017
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Ingår i: ChemistryOpen. - : WILEY-V C H VERLAG GMBH. - 2191-1363. ; 6:4, s. 484-487
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Tidskriftsartikel (refereegranskat)abstract
- The development of a protocol for the reductive functionalization of amides into N-sulfonylformamidines is reported. The one-pot procedure is based on a mild catalytic reduction of tertiary amides into the corresponding enamines by the use of Mo(CO)(6) (molybdenum hexacarbonyl) and TMDS (1,1,3,3-tetramethyldisiloxane). The formed enamines were allowed to react with sulfonyl azides to give the target compounds in moderate to good yields.
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| 12. |
- Trillo, Paz, et al.
(författare)
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Straightforward alpha-Amino Nitrile Synthesis Through Mo(CO)(6)-Catalyzed Reductive Functionalization of Carboxamides
- 2018
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Ingår i: Angewandte Chemie International Edition. - : Wiley-VCH Verlagsgesellschaft. - 1433-7851 .- 1521-3773. ; 57:38, s. 12347-12351
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Tidskriftsartikel (refereegranskat)abstract
- The selective reduction of amides into an intermediate hemiaminal catalyzed by Mo(CO)(6) together with the inexpensive and easy to handle TMDS (1,1,3,3-tetramethyldisiloxane) as reducing agent, followed by subsequent trapping of the hemiaminal with a cyanide source, allows for the straightforward synthesis of alpha-amino nitriles. The methodology presented here, displays high levels of chemoselectivity allowing for the reduction of amides in the presence of functional groups such as ketones, imines, aldehydes, and acids, which affords a simple route for the synthesis of alpha-amino nitriles with a broad scope of functionalities in high yields. Furthermore, the applicability of this methodology is demonstrated by scale up experiments and by derivatization of the target compounds into synthetically interesting products. The selective cyanation is successfully applied in late stage functionalizations of amide containing drugs and prolinol derivatives.
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| 13. |
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