01.11.2018

Research

Our group focuses mainly on developing, understanding and applying catalytic methods in organic synthesis. This is covered by three main fields of study: total synthesis, method development and mechanistic studies. In spite of massive advances in the field, many catalytic transformations still suffer from relatively narrow substrate scope. Sometimes, this is simply because the catalysts are clearly suboptimal for the purpose. We try to solve these issues by developing rapid, reliable and mild methods with wide substrate scopes.

Both the Department of Chemistry and the close-by Nanoscience Center at the University of Jyväskylä provide us with large-scale instrumentation. This includes, among others, four Bruker Avance NMR instruments (300, 400, 500 and 800 MHz), four MS instruments (including a state-of-the-art LC/Q-TOF), four XRD instruments, and a four-port MBraun UNILab glove box. In addition to these, our group has a CombiFlash RF unit, a Waters HPLC system, Shimadzu reverse phase Prep-LC, two Agilent GCs and an MBraun MB-SPS 800 automated solvent purification system.  We also have direct access to the national supercomputers that are maintained by CSC – IT Center for Science Ltd (ORCA, Gaussian and Turbomole available), as well as a local Schrödinger Maestro licence.

Our international  collaborators include Dr. Imre Pápai (Hungarian Academy of Sciences - computational chemistry) and Prof. Georgios Vassilikogiannakis (University of Crete, Greece). Nationally, we are collaborating closely with the groups of Prof. Reko Leino (Åbo Akademi - organometallic chemistry), Prof. Timo Repo (University of Helsinki - novel catalytic approaches in organocatalysis), Prof. Rikkert Wierenga (University of Oulu - structural enzymology with enolizing enzymes), Prof. Kari Rissanen (University of Jyväskylä - structural characterization and X-ray crystallography), Dr. Karoliina Honkala (University of Jyväskylä - computational heterogeneous catalysis) and Dr. Katri Laatikainen (Lappeenranta University of Technology).

Natural Product Total Synthesis

Total synthesis has been one of the key research areas since the inception of the group. Not only does it provide a true acid test for new reactions but it also points towards gaps to be filled in the stockpile of chemical transformations. Among smaller targets (oxidized terpenes, polyketide fragments and alkaloids) we are also pursuing total synthesis of the highly complex, cytotoxic marine toxin pectenotoxin-2, which keeps providing us with numerous opportunities for chemical discoveries.

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  • Mäkinen, M. E., Mallik, R., Siitonen, J. H., Kärki, K., Pihko, P. M. 'Towards Waltheriones C and D: Synthesis of the Oxabicyclic Core' Synlett201728, 1209
  • Siitonen, J. H., Pihko, P. M. 'Total Synthesis of (+)-Greek Tobacco Lactone' Synlett2014, 25, 1888
  • Kemppainen, E. K.; Sahoo, G.; Valkonen, A.; Pihko, P. M. 'Mukaiyama–Michael Reactions with Acrolein and Methacrolein: A Catalytic Enantioselective Synthesis of the C17–C28 Fragment of Pectenotoxins'. Org. Lett. 201214, 1086
  • Helmboldt, H.; Aho, J. E.; Pihko, P. M. ’Synthetic Studies Toward Pectenotoxin 2. Part II. Synthesis of the CDE and CDEF Ring Systems.’ Org. Lett. 2008, 10, 4179

Method Development and Catalysis

In broad terms, the group very actively engaged in the development of novel catalytic methods for organic synthesis. Our work covers organo-, enzyme- and metal catalysis. We are especially interested in rational organocatalyst design and enzyme-mimetic systems to achieve efficient and enantioselective transformations.

  • Claraz, A.; Sahoo, G.; Berta, D.; Madarász, Á.; Pápai, I.; Pihko, P. M.* 'A catalyst designed for the enantioselective construction of methyl- and alkyl-substituted tertiary stereocentres.' Angew. Chem. Int. Ed. 2015, 55, 669
  • Nimje, R. Y.; Leskinen, M. V.; Pihko, P. M. 'Three-Component Palladium-Catalyzed Oxidative C–C Coupling Reaction: A Domino Process in Two Dimensions.' Angew. Chem. Int. Ed., 2013, 52, 4818
  • Probst, N.; Madarász, Á.; Valkonen, A.; Pápai, I.; Rissanen, K.; Neuvonen, A.; Pihko, P. M. 'Cooperative Assistance in Bifunctional Organocatalysis: Enantioselective Mannich Reactions with Aliphatic and Aromatic Imines.' Angew. Chem. Int. Ed. 2012, 51, 8495

Mechanistic Studies and Physical Organic Chemistry

Rigorous mechanistic studies are used to better grasp the details of novel catalytic reactions. In numerous cases we have shown how mechanistic understanding is of paramount importance when optimizing catalytic systems. With both computational and experimental methods, both reliability and scope of the transformations can be vastly improved. Computational work is done in a tight collaboration with the Pápai and Honkala groups.

  • Tuokko, S.; Honkala, K.; Pihko, P. M. 'Pd/C Catalyzed Hydrosilylation of Enals and Enones with Triethylsilane: Conformer Populations Control the Stereoselectivity.' ACS Catalysis, 2017, 7, 480
  • Leskinen, M. V.; Madarász, A.; Yip, K.-T.; Vuorinen, A.; Pápai, I.; Neuvonen A. J.; Pihko, P. M.; 'Cross-Dehydrogenative Couplings between Indoles and β-Keto Esters: Ligand-Assisted Ligand Tautomerization and Dehydrogenation via a Proton-Assisted Electron Transfer to Pd(II).' J. Am. Chem. Soc., 2014, 136, 6453
  • Sahoo, G.; Rahaman, H.; Madarász, Á.; Pápai, I.; Melarto, M.; Valkonen, A.; Pihko, P. M. 'Dihydrooxazine Oxides as Key Intermediates in Organocatalytic Michael Reactions of Aldehydes to Nitroalkenes.' Angew. Chem. Int. Ed. 2012, 51, 13144