Organic synthesis and homogeneous catalysis is the primary focus of Bjørsvik research group. The main goal of the most of the research in progress in the group are to develop new and better catalysts and cataytic processes, focusing both on improvement of synthetic processes and methods as well as the design of new ligands with the goal to improved selectivity and activity of the final catalyst.
The group are currently working mainly with the two transition metals ruthenium and palladium with N-heterocyclic carbenes (NHCs) as the most important activating and stabilizing ligand. This work includes also efforts to secure the NHC ligand with a pendant arm to the surface of polymer particles, that can be of nanometer to micrometer size.
In addition to the development of catalysts, we develop new pathways in which transition metal catalysis are included as an important part of total synthesis. We are particularly interested in the synthesis of N-heterocyclic compounds with biological activity and various antioxidants.
The synthesis of N-heterocycles
Within this research activity, the molecular scaffolds of particular interests are benzo[c]cinnolines, carbazoles, and imidazoles. A recent NFR report discloses a summary of some of our recent works within this activity. The imidazoles are of particular interest as such compounds can be used as precursors for NHC ligands used in organometallics for various catalysts, for example for olefin metathesis, Suzuki cross-coupling, and oxidation catalysts.
Oxidation and Free Radicals in Organic Synthesis
Free organic radicals for synthetic applications, development of green chemistry methods for the oxidation reactions in organic synthesis has been an long standing research activity in the research group. This research activity involves also studies of antioxidants and development of new total syntheses of such compounds.
Development and investigation of continuous flow organic synthesis reactor systems is an important long standing project in the group. We have successfully developed a novel approach for flow chemistry that is realized in a milli-reactor system that we have named multi-jet oscillation disk (MJOD) milli reactor system. A patent application was submitted (2005) for this system, and a company that was named Fluens Synthesis AS was established.
- KJEM131 Organic Synthesis and Analysis
- KJEM232 Experimental organic synthesis
- KJEM233 Organic mass spectrometry (past)
- KJEM335 Physical Organic Chemistry (past)
- Organometallic reactions in organic synthesis
- N-heterocyclic carbenes in synthesis
- Heterocyclic chemistry
- Experimental Design and Modelling in Organic Synthesis
- Free Radical Reactions in Synthetic Organic Chemistry
- Instrumental methods in organic synthesis
- 2016. Synthesis of the Carbazole Scaffold Directly from 2-Aminobiphenyl by Means of Tandem C–H Activation and C–N Bond Formation. European Journal of Organic Chemistry. 5474-5479. doi: 10.1002/ejoc.201601191
- 2016. Continuous flow synthesis concatenated with continuous flow liquid–liquid extraction for work- up and purification: selective mono- and di- iodination of the imidazole backbone. Reaction Chemistry & Engineering. 1: 436-444. doi: 10.1039/c6re00091f
- 2016. Indium powder as the reducing agent in the synthesis of 2-amino-1,1′-biphenyls. Tetrahedron Letters. 57: 1224-1226. doi: 10.1016/j.tetlet.2016.02.007
- 2016. A highly efficient Pd(PPh3)4-catalyzed Suzuki cross-coupling method for the preparation of 2-nitrobiphenyls from 1-chloro-2-nitrobenzenes and phenylboronic acids. European Journal of Organic Chemistry. 2016: 1344-1354. doi: 10.1002/ejoc.201501487
- 2016. Continuous flow synthesis of the iodination agent 1,3-diiodo-5,5-dimethyl-imidazolidine-2,4-dione telescoped with semi-continuous product isolation. Reaction Chemistry & Engineering. 1: 379-386. doi: 10.1039/c6re00051g
- 2015. The Baeyer-Villiger oxidation versus aromatic ring hydroxylation: Competing organic peracid oxidation mechanisms explored by multivariate modelling of designed multi-response experiments. Journal of Physical Organic Chemistry. 28: 619-628. doi: 10.1002/poc.3462
- 2015. Controlling the course of a two-way switchable Pd-catalyzed process by means of empirical multivariate models. ChemCatChem. 7: 2196-2205. doi: 10.1002/cctc.201500234
- 2015. Scope and mechanistic limitations of a sonogashira coupling reaction on an imidazole backbone. European Journal of Organic Chemistry. 2015: 4658-4666. doi: 10.1002/ejoc.201500520
- 2015. 4-alkylated silver-N-heterocyclic carbene (NHC) complexes with cytotoxic effects in leukemia cells. ChemMedChem. 10: 1522-1527. doi: 10.1002/cmdc.201500234
- 2015. Stille cross-coupling for the functionalization of the imidazole backbone: Revisit, improvement, and applications of the method. European Journal of Organic Chemistry. 2015: 3506-3512. doi: 10.1002/ejoc.201500328
- 2014. Continuous flow olefin metathesis using a multijet oscillating disk reactor as the reaction platform. Organic Process Research & Development. 18: 1509-1515. doi: 10.1021/op500223e
- 2014. Synthesis of imidazole alkaloids originated in marine sponges. Studies in Natural Products Chemistry. 42: 33-57. doi: 10.1016/B978-0-444-63281-400002-1
- 2014. Multivariate optimization of a cyclopropanation, the key step in the synthesis of 3,3,4,4-tetraethoxybut-1-yne. Organic Process Research & Development. 18: 891-896. doi: 10.1021/op5001012
- 2013. A Three-Way Switchable Process for Suzuki Cross-Coupling, Hydrodehalogenation, or an Assisted Tandem Hydrodehalogenation and Suzuki Cross-Coupling Sequence. Advanced Synthesis and Catalysis. 355: 3231-3243. doi: 10.1002/adsc.201300395
- 2013. Fast halogenation of some N-heterocycles by means of N,N-dihalo-5,5-dimethylhydantoin. Advanced Synthesis and Catalysis. 355: 499-507. doi: 10.1002/adsc.201200723
- 2012. Extraction, isolation, and purification of analytes from samples of marine origin - A multivariate task. Journal of chromatography. B. 910: 46-53. doi: 10.1016/j.jchromb.2012.06.038
- 2012. Synthesis of phenylboronic acids in continuous flow by means of a multijet oscillating disc reactor system operating at cryogenic temperatures. Organic Process Research & Development. 16: 1121-1130. doi: 10.1021/op3000493
- 2012. Organocatalyzed epoxidation of alkenes in continuous flow using a multi-jet oscillating disk reactor. ChemSusChem. 5: 261-265. doi: 10.1002/cssc.201100262
- 2012. Separation of reaction product and palladium catalyst after a heck coupling reaction by means of organic solvent nanofiltration. ChemSusChem. 5: 188-193. doi: 10.1002/cssc.201100355
- 2011. Multijet Oscillating Disc Millireactor: A Novel Approach for Continuous Flow Organic Synthesis. Organic Process Research & Development. 15: 997-1009. doi: 10.1021/op2000699
- 2011. Synthetic Route Discovery and Introductory Optimization of a Novel Process to Idebenone. Organic Process Research & Development. 15: 673-680. doi: 10.1021/op200051v
- 2010. A switchable oxidation process leading to two various versatile pharmaceutical intermediates. Organic Process Research & Development. 14: 1379-1384. doi: 10.1021/op100185x
- 2010. An optimized process to 10-bromo-1-decanol. Organic Process Research & Development. 14: 1215-1220. doi: 10.1021/op100143t
- 2009. Synthesis of a new bidentate NHC–Ag(I) complex and its unanticipated reaction with the Hoveyda–Grubbs first generation catalyst. Tetrahedron. 65: 7186-7194. doi: 10.1016/j.tet.2009.05.095
- 2009. A novel simple and efficient bromination protocol for activated arenes. Tetrahedron Letters. 50: 831-833. doi: 10.1016/j.tetlet.2008.12.016
- 2007. Green and efficient synthesis of bidentate Schiff base Ru catalysts for olefin metathesis. Journal of Organic Chemistry. 72: 3561-3564. doi: 10.1021/jo070164z
- 2007. The first imidazolium-substituted metal alkylidene. Organometallics. 26: 4383-4385. doi: 10.1021/om700590v
- 2007. Ruthenium alkylidene complexes of Chelating amine Ligands. Organometallics. 26: 5803-5814. doi: 10.1021/om070219n S0276-7333(07)00219-1
- 2006. Quantitative structure-activity relationships of ruthenium catalysts for olefin metathesis. Journal of the American Chemical Society. 128: 6952-6964. doi: 10.1021/ja060832i
- 2006. Efficient and green telescoped process to 2-methoxy-3-methyl-[1,4]benzoquinone. Journal of Organic Chemistry. 71: 1703-1706. doi: 10.1021/jo0522512
- 2005. A novel efficient deoxygenation process for N-heteroarene N-oxides. Journal of Organic Chemistry. 70: 3218-3224.
- 2005. Synthesis of methoxy-substituted phenols by peracid oxidation of the aromatic ring. Journal of Organic Chemistry. 70: 7290-7296.
- 2005. Synthesis of 2-Nitro and 2,2’-Dinitro Biphenyls by means of the Suzuki Cross-Coupling reaction. Journal of Organic Chemistry. 70: 9591-9594.
- 2004. Online Spectroscopy and Multivariate Data Analysis as a Combined Tool for Process Monitoring and Reaction Optimization. Organic Process Research & Development. 8: 495-503.
- 2004. Investigations of a novel process to the framework of benzo[c]cinnoline. Journal of Organic Chemistry. 69: 7720-7727.
- 2004. Nitroarene Catalyzed Oxidation with Sodium percarbonate or Sodium perborate as the Terminal Oxidant. Tetrahedron Letters. 45: 8615-8620.
- 2002. N-Acylation Reactions Performed in Aqueous Reaction Medium. Synthesis of Iodixanol. Organic Process Research & Development. 6: 113-119.
- 2002. Organic Processes to Pharmaceutical Chemicals Based on Fine Chemicals from Lignosulfonates. Organic Process Research & Development. 6: 279-290.
- 2002. A New Modified Montanari Oxidation Process by Means of Chlorine Dissolved in the reaction Solvent as Oxidant and TEMPO as Catalyst: Oxidation of 3-S-Quinuclidinol to 3-Quinuclidinone. Organic Process Research & Development. 6: 197-200.
- 2002. Carboxylic acids from methyl aryl ketones by means of a new composite aerobic oxidation process. Tetrahedron Letters. 43: 4985-4987.
- 2002. A Highly Selective Aerobic Oxidation Process Catalysed by Electron Deficient Nitroarenes via Single Electron Transfer Processes. Journal of Organic Chemistry. 67: 7493-7500.
- 2002. Highly Selective and Efficient Conversion of Alkyl Aryl and Alkyl Cyclopropyl Ketones to Aromatic and Cyclopropane Carboxylic Acids by Aerobic Catalytic Oxidation: A Free-Radical Redox Chain Mechanism. Synlett. 610-612.
- 2001. A Bromine Catalysed Free-Radical Oxidation of Acetamides From Primary and Secondary Alkylamines by H_2O_2. Chemical Communications. 523-524.
- 2001. New Selective Oxidation Reactions by Nitroarenes in Basic Medium Involving Electron Transfer Processes. Organic Process Research & Development. 5: 136-140.
- 2001. A Selective Process for N-Alkylation in Competition with O-Alkylation. Boric acid as a Cheap and Effective Protecting Group Applicable for Industrial Scale Synthetic Processes. Organic Process Research & Development. 5: 472-478.
- 2001. Process for the production of iodinated organic x-ray contrast agents. US Patent. US 6,232,499.
- 2000. Organic Process Research and Development by Means of Statistical Experimental Design, Multivariate Modelling, and Mechanistic Interpretation. La Chimica e l'Industria. 82. 8 pages.
- 2000. High Selectivity in the Oxidation of Mandelic acid derivatives and in O-methylation of protocatechualdehyde. New Processes for Synthesis of Vanillin, iso-Vanillin and Heliotropin. Organic Process Research & Development. 4. 9 pages.
- 1999. Fine Chemicals from Lignosulfonates. 1. Synthesis of Vanillin by Oxidation of Lignosulfonate. Organic Process Research & Development. 3: 330-340.
- 1999. Fine Chemicals from Lignosulfonates 2. Synthesis of Veratric acid from Acetoveratrone. Organic Process Research & Development. 3: 341-346.
- 1999. Electrophilic Aromatic Alkylation by Hydroperoxides, Dompetition Between Ionic and Radical Mechanism. Journal of Organic Chemistry. 64: 8812-8815.
- 1999. Polar Effects in Free-Radical Reactions. the Paradox of Reductions of alkyl Iodides and Reductive alkylation of Alkenes by Strong Oxidants (t-BuOOH,Pb(OAc)4. Journal of the American Chemical Society. 121: 7760-7765.
- 1999. Stability of Iodixanol=3,3',5,5'-tetrakis(2,3-dihydroxypropylcarbamoyl)2,2',4,4',6,6'-hexaiodo-N,N'-(2-hydroxypropane-1,3-diyl)diacetanilide towards acid, base, oxygen, heat and light. Journal of Clinical Pharmacy and Therapeutics. 24: 227-235.
- 2010. IUPAC ICOS-18 Proceedings. Kjemisk institutt, Universitetet i Bergen, Bergen. 114 pages.
- 2009. Introduction to design and modelling of organic reactions and processes. Lecture notes from course for PhD students and researchers of the research training network InSolEx. utgit av forfatterne selv, Universitetet i Bergen, Kjemisk instutt. 50 pages.
- 2006. Organic Free Radicals. Program and abstract collection from the EUCHEM conference on organic free radicals, Scandinavian collaboration for the 2006 conference. Kjemisk institutt, Universitetet i Bergen, Bergen.
- 2002. Introduction to design and modelling of organic reactions and processes. Optimum Accipe (H.-R. Bjørsvik), Bergen. 51 pages.
- 2007. Data Analysis: Calibration of NIR Instruments by PLS Regression. Chapter 9, pages 189-206. In:
- 2007. Handbook of Near-Infrared Analysis, Third Edition. CRC Press. 832 pages. ISBN: 084937393X.
- 2001. Chapter 8: Data Analysis:PLS Calibration of NIR instruments by PLS regression. 185-207. In:
- 2001. Handbook of Near-Infrared Analysis Second Edition, Revised and Expanded. ISBN: 0-8247-0534-3.
- Alexander H. Sandtorv, Karl Wilhelm Törnroos, and Hans-René Bjørsvik.* Stille Cross-Coupling for the Functionalization of the Imidazole Backbone: Revisit, Improvement, and Applications of the Method. Eur. J. Org. Chem. 2015, 3506–3512.
- Alexander H. Sandtorv and Hans-René Bjørsvik.* Controlling the course of a two-way switchable Pd-catalyzed process by means of empirical multivariate models. ChemCatChem 2015, 7, 2196 – 2205.
- Cristian Gambarotti and Hans-René Bjørsvik.* The Baeyer-Villiger oxidation versus aromatic ring hydroxylation: Competing organic peracid oxidation mechanisms explored by multivariate modelling of designed multi-response experiments. Journal of Physical Organic Chemistry 2015, 28, 619-628.
- Alexander H. Sandtorv and Hans-René Bjørsvik.* Scope and Mechanistic Limitations of a Sonogishara Coupling on the Imidazole Backbone. Eur. J. Org. Chem. 2015, 4658-4666.
- Alexander H. Sandtorv, Calum Leitch, Siv Lise Bedringaas, Bjørn Tore Gjertsen and Hans-René Bjørsvik.* Alkylated Silver–N-Heterocyclic Carbene (NHC) Complexes with Cytotoxic Effects in Leukemia Cells. ChemMedChem 2015, 10, 1522 – 1527, (cover)
- Vijayaragavan Elumalai and Hans-René Bjørsvik.* Indium powder as a reducing agent in the synthesis of 2-amino-1,1'-biphenyls. Tetrahedron Letters 2016, 57, 1224–1226.
- Vijayaragavan Elumalai, Alexander H. Sandtorv, and Hans-René Bjørsvik.* A Highly Efficient Pd(PPh3)4-Catalyzed Suzuki Cross-Coupling Method for the Preparation of 2-Nitrobiphenyls from 1-Chloro-2-Nitrobenzenes and Phenylboronic acids. European Journal of Organic Chemistry 2016, 1344-1354.
- Marta Ferreri, Audun Drageset, Cristian Gambarotti, and Hans-René Bjørsvik.* Continuous flow synthesis telescoped with semi-continuous product isolation for multi-100 g scale production of the iodination agent 1,3-diiodo-5,5-dimethyl-imidazolidine-2,4-dione. Reaction Chemistry & Engineering 2016, RE-ART-03-2016-000051. (in press)
- Organic Chemistry and Synthesis
- Heterocyclic chemistry, in particular N-heterocycles
- Oxidation and antioxidants
- Free radical chemistry
- NHC ligands and transition metals for catalysis
- Flow chemistry technologies and flow synthesis
- Microwave in organic synthesis
- Optimization and investigation of organic syntheses and processes by means of statistical experimental design and multivariate regression
- Fiber optical spectroscopy for reaction monitoring
A thesis project in organic synthesis will deal with the development of one or more steps of a synthesis leading either to a key intermediate or to a target molecule of a total synthesis. Moreover, other investigations may be required in order to support a proposal for a reaction mechanisms.
The synthetic task can be: (1) investigation of an one step reaction, (2) design and development of a multi-step synthesis of either academic or commercial industrial interest, or (3) a study that involves investigation of a synthetic transformation where the goal is to maximize the profit of an industrial synthesis, improve the yield and / or the selectivity. Target molecule or intermediate can be an important intermediate products or preferably a biologically active compound that can be used as a pharmaceutical chemical. Usually, the target molecule, or model molecule is a N-heterocyclic natural compound.
A project in advanced spectroscopy and organic synthesis will start out with searching the chemical literature and studies of previous research work. This is followed by introductory experiments in the laboratory, where techniques for synthesis laboratory will be used (performing reaction under different conditions, filtration, drying, extraction, crystallization, distillation, flash chromatography, thin layer chromatography, etc.). Of instrumental analytical methods, different chromatographic methods such as GC, GC-MS and HPLC can be necessary for quantification.
Various pectroscopy and spectrometry are of paramount importance in this project, and will involve the utilization of mass spectrometry (MS), infrared spectroscopy (ATR FT-IR) and nuclear magnetic resonance (1H NMR and 13C NMR and other nucleuses if necessary) will be used for identification and structure elucidation of target products and eventually side- and by-products that have been produced.
Keywords: Synthesis, N-heterocyclic compounds, natural products, metal organic reactions, 1H NMR, 13C NMR, MS, FT-IR, fiber optical raman, fiber optical Near-IR, reaction monitoring