1. Total Synthesis of Vinigrol Using a New Strategic Concept, 2. Asymmetric Alkynyl-Substituted Trimethylenemethane [6+3] Cycloadditions, 3. Total Synthesis of Bryostatin 3 Using a New Strategic Concept

• Applicant: Olesya Kuzmina, Ph.D.
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2015 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 273747462

• Final Report Year: 2017

Final Report Abstract

In summary, it was shown that the core of the natural product Vinigrol could be achieved via a novel Pd-catalyzed [6+3] cycloaddition of a trimethylenemethane (TMM) derivative to a substituted tropone, followed by a novel ring expansion process. Although, the synthetic routes to the precursors need some optimisation. It was also found that asymmetric alkynylsubstited trimethylenemethane [6+3] cycloaddition is a convenient method to access molecules with quarternary centres. Thus, the synthetic route to the tertiary alkynylsubstituted TMM donor was investigated. Finally, it was discovered that the total synthesis of the natural product Bryostatin 3 could be shorten by using a new strategy which allows to achieve a northern fragment B’ in 9 steps instead of 13. By the end of the poject it was only one step left to finish the total synthesis of Bryostatin 3. If successful, the total synthesis will include 33 steps (24 longest linear) compare to previously reported 88 total steps (43 longest linear). It was also shown that this strategy opens a convenient access to analogs of bryostatin 3 via late stage derivatization.

Publications

• Iron-Catalyzed Cross-Coupling of N-Heterocyclic Chlorides and Bromides with Arylmagnesium Reagents. Org. Lett. 2012, 14, 4818 – 4821
  Kuzmina, O. M.; Steib, A. K.; Flubacher, D. & Knochel, P.
  
• Efficient Chromium(II)-Catalyzed Cross-Coupling Reactions between Csp2-Centers. J. Am. Chem. Soc. 2013, 135, 15346 – 15349
  Steib, A. K.; Kuzmina, O. M.; Fernandez, S.; Flubaсher, D. & Knochel, P.
  
• Ligand- Accelerated Fe- and Co-Catalyzed Cross-Coupling Reactions between N-Heterocyclic Halides and Aryl Magnesium Reagents. Angew. Chem. Int. Ed. 2013, 52, 4945 – 4949
  Kuzmina, O. M.; Steib, A. K.; Markiewicz, J. T.; Flubacher, D. & Knochel, P.
  
• Room-Temperature Chromium(II)-Catalyzed Direct Arylation of Pyridines, Aryl Oxazolines and Imines Using Arylmagnesium Reagents. Org. Lett. 2014, 16, 5208 – 5211
  Kuzmina, O. M. & Knochel, P.
  
• Synthesis of Novel 14-Membered Cyclic bis-Semicarbazones. Tetrahedron Lett. 2014, 55, 5481 – 5485
  Shutalev, A. D.; Fesenko, A. A.; Kuzmina, O. M.; Volov, A. N.; Albov, D. V.; Chernyshev, V. V. & Zamilatskov, I. A.
  
• Chemoselective Chromium(II)-Catalyzed Cross-Coupling Reactions of Dichlorinated Heteroaromatics with Functionalized Aryl Grignard Reagents. Chem. Eur. J. 2015, 21, 1961 – 1965
  Steib, A. K.; Kuzmina, O. M.; Fernandez, S.; Malhotra, S. & Knochel, P.
  
• Chromium(II)-Catalyzed Amination of N-Heterocyclic Chlorides with Magnesium Amides. Synlett. 2015, 26, 1049 – 1054
  Steib, A. K.; Fernandez, S.; Kuzmina, O. M.; Corpet, M.; Gosmini, C. & Knochel, P.
  
• Practical Iron- and Cobalt-Catalyzed Cross-Coupling Reactions between N-Heterocyclic Halides and Aryl or Heteroaryl Magnesium Reagents. Chem. Eur. J. 2015, 21, 8242 – 8249
  Kuzmina, O. M.; Steib, A. K.; Fernandez, S; Boudot, W.; Markiewicz, J. T. & Knochel, P.
  
• Recent Advances in Iron-Catalyzed Csp2-Csp2 Cross-Couplings. Synthesis 2015, 47, 1696 – 1705
  Kuzmina, O. M.; Steib, A. K.; Moyeux, A.; Cahiez, G. & Knochel, P.