Synthesis of P-Chiral Phosphanes from Low-Coordinate Phosphorus Compounds as Bidentate Ligands in Stereoselective Catalysis

• Applicants: Professorin Dr. Evamarie Hey-Hawkins; Professor Dr. Johannes Gerardus de Vries, since 2/2021
• Subject Area: Inorganic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 411421782

• Final Report Year: 2024

Final Report Abstract

Some chemical compounds can exist in two mirror images called enantiomers. This is called chirality. Their chemical properties of enantiomers are the same but in their interaction with biological systems such as enzymes and receptors, which are also chiral, the two enantiomers will behave differently. For that reason, it is important that pharmaceuticals are prepared as single enantiomers. In the past this was done by a cumbersome separation of racemates (the 50/50 mixtures of the two enantiomers), but it is of course much better to immediately synthesise only a single enantiomer. For this, enantioselective catalysis is a highly efficient methodology. The problem is that there are no catalysts that work for all known reactions. The catalysts are organometallic complexes that consist of a transition metal and one or more ligands. The catalyst diversity is largely created by the chiral ligand and hence the synthesis of new classes of ligands is extremely useful as it enlarges the pool of catalysts that can be chosen from. In this project two classes of ligands were investigated. Ligands based on phosphanorbornanes did not induce sufficient selectivity to the products and hence a new class of ligands called diphosphazanes was developed. These ligands were highly successful in enantioselective hydrogenation reactions leading to enantiopure intermediates for pharmaceuticals. In the third part of this research it was successfully attempted to replace the expensive transition metals such as rhodium, iridium and ruthenium by cobalt. Also, with these cobalt-based catalyst it was possible to prepare a series of pharma intermediates.

Publications

• P-Chirogenic Diphosphazanes with Axially Chiral Substituents and Their Use in Rh-Catalyzed Asymmetric Hydrogenation. The Journal of Organic Chemistry, 85(22), 14537-14544.
  Moritz, Jan-Ole; Chakrabortty, Soumyadeep; Müller, Bernd H.; Spannenberg, Anke & Kamer, Paul C. J.
  
• A Simple Synthetic Route to [Rh(acac)(CO)(NHC)] Complexes: Ligand Property Diagnostic Tools and Precatalysts. European Journal of Inorganic Chemistry, 2021(34), 3506-3511.
  Guillet, Sébastien G.; Pisanò, Gianmarco; Chakrabortty, Soumyadeep; Müller, Bernd H.; de Vries Johannes, G.; Kamer, Paul C. J.; Cazin, Catherine S. J. & Nolan, Steven. P.
  
• Recent developments in asymmetric hydroformylation. Catalysis Science & Technology, 11(16), 5388-5411.
  Chakrabortty, Soumyadeep; Almasalma, Ahmad A. & de Vries Johannes, G.
  
• The solvent determines the product in the hydrogenation of aromatic ketones using unligated RhCl3 as catalyst precursor. Catalysis Science & Technology, 11(23), 7608-7616.
  Chakrabortty, Soumyadeep; Rockstroh, Nils; Bartling, Stephan; Lund, Henrik; Müller, Bernd H.; Kamer, Paul C. J. & de Vries Johannes, G.
  
• Betti base derived P-stereogenic phosphine-diamidophosphite ligands with a single atom spacer and their application in asymmetric catalysis. Catalysis Science & Technology, 12(5), 1392-1399.
  Chakrabortty, Soumyadeep; Konieczny, Katharina; Müller, Bernd H.; Spannenberg, Anke; Kamer, Paul C. J. & de Vries Johannes, G.
  
• Access to Enantiomerically Pure P-Chiral 1-Phosphanorbornane Silyl Ethers. Molecules, 28(17), 6210.
  Ramazanova, Kyzgaldak; Chakrabortty, Soumyadeep; Kallmeier, Fabian; Kretzschmar, Nadja; Tin, Sergey; Lönnecke, Peter; de Vries Johannes, G. & Hey-Hawkins, Evamarie
  
• Cobalt‐Catalyzed Asymmetric Hydrogenation: Substrate Specificity and Mechanistic Variability. Angewandte Chemie International Edition, 63(10).
  Chakrabortty, Soumyadeep; de Bruin, Bas & de Vries Johannes, G.
  
• Cobalt‐Catalyzed Enantioselective Hydrogenation of Trisubstituted Carbocyclic Olefins: An Access to Chiral Cyclic Amides. Angewandte Chemie International Edition, 62(26).
  Chakrabortty, Soumyadeep; Konieczny, Katharina; de Zwart, Felix, J.; Bobylev, Eduard. O.; Baráth, Eszter; Tin, Sergey; Müller, Bernd H.; Reek, Joost N. H.; de Bruin, Bas & de Vries Johannes, G.
  
• Concise synthesis of Azilect via cobalt-catalyzed enantioselective hydrogenation in a bio-based solvent. Catalysis Science & Technology, 13(23), 6668-6674.
  Chakrabortty, Soumyadeep; de Zwart, Felix, J.; Snabilié, Demi D.; Balaraman, Ekambaram; Reek, Joost N. H.; de Bruin, Bas & de Vries Johannes, G.
  
• Rh-Catalyzed Enantioselective Hydrogenation of Di-and Tri-Substituted Enamides Enabled by Easily Tunable P-Stereogenic N-Phosphinyl Phosphoramidite Ligands. ACS Catalysis, 13(18), 12030-12040.
  Chakrabortty, Soumyadeep; Konieczny, Katharina; Moritz, Jan-Ole; Zheng, Shasha; Tin, Sergey; Müller, Bernd H. & de Vries Johannes, G.
  
• Ru‐Catalyzed Direct Asymmetric Reductive Amination of Bio‐Based Levulinic Acid and Ester for the Synthesis of Chiral Pyrrolidinone. ChemSusChem, 16(9).
  Chakrabortty, Soumyadeep; Zheng, Shasha; Kallmeier, Fabian; Baráth, Eszter; Tin, Sergey & de Vries Johannes, G.
  
• Synthesis of P-stereogenic 1-phosphanorbornane-derived phosphine–phosphite ligands and application in asymmetric catalysis. RSC Advances, 13(49), 34439-34444.
  Ramazanova, Kyzgaldak; Chakrabortty, Soumyadeep; Müller, Bernd H.; Lönnecke, Peter; de Vries Johannes, G. & Hey-Hawkins, Evamarie