Cascade transformations of unsaturated alcohols catalyzed by bifunctional ruthenium complexes

• Applicant: Professor Dr. Edgar Haak
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2014 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 265182801

• Final Report Year: 2023

Final Report Abstract

The generation of molecular complexity is a central task of modern synthetic chemistry. In this context, transition-metal-catalyzed cascade transformations of readily available starting materials offer maximum efficiency and atom economy. We develop cascade processes that enable rapid access to bioactive natural products and natural product-like compounds for drug research as well as complex molecular structures for new functional materials. The use of rationally designed, multifunctional catalysts that can selectively catalyze different conversions of a given substrate type enables divergent reaction cascades and maximum product diversity. The focus of the funded project was on the development of ruthenium-catalyzed cascade reactions and their application in the synthesis of natural product-inspired alkaloid and terpenoid analogues. The developed catalytic reactions allow for the efficient conversion of readily available unsaturated alcohols to access important carbo- and heterocyclic molecular frameworks. New short routes to functionalized pyrazoles, pyrroles, indoles, indolines, carbazoles, tryptolines, cyclohepta[b]indoles, indazoles, pyridines, quinolines, furanes, pyranes, norbornenes, cyclodendralenes, carbopolycycles and other types of compounds could be created. Natural product-inspired molecular architectures are easily accessible in one pot by multicomponent processes based on the new cascade reactions. In addition, some of the new catalytic reactions have been applied as key steps in natural product synthesis.

Publications

• Ruthenium‐Catalyzed Synthesis of 2,3‐Cyclo[3]dendralenes and Complex Polycycles from Propargyl Alcohols. Angewandte Chemie International Edition, 54(13), 4097-4101.
  Thies, Nora & Haak, Edgar
  
• Application of a Ruthenium-Catalyzed Allylation–Cycloisomerization Cascade to the Synthesis of (±)-Herbindole A. Synlett, 28(06), 701-704.
  Haak, Edgar; Thies, Nora & Stürminger, Martin
  
• Transition‐Metal‐Catalyzed Transformations of 1‐Alkenylpropargyl Alcohols and Esters: Valuable Cascade Reactions for Increasing Structural Complexity. European Journal of Organic Chemistry, 2017(5), 940-949.
  Haak, Edgar
  
• Complex Polycycles from Simple Propargyl Alcohols through Ruthenium-Catalyzed Cascade Reactions and One-Pot Procedures. Synthesis, 50(04), 742-752.
  Jäckel, Elisabeth; Kaufmann, Julia & Haak, Edgar
  
• Modern Annulation Strategies for the Synthesis of Cyclo[b]fused Indoles. Synlett, 30(03), 245-251.
  Haak, Edgar
  
• Ruthenium‐Catalyzed Cascade Annulation of Indole with Propargyl Alcohols. Angewandte Chemie International Edition, 57(20), 5908-5911.
  Kaufmann, Julia; Jäckel, Elisabeth & Haak, Edgar
  
• Ruthenium-catalyzed formation of pyrazoles or 3-hydroxynitriles from propargyl alcohols and hydrazines. Arkivoc, 2019(4), 91-101.
  Kaufmann, Julia; Jäckel, Elisabeth & Haak, Edgar
  
• Triaminocyclopentadienyl Ruthenium Complexes – New Catalysts for Cascade Conversions of Propargyl Alcohols. Chemistry – A European Journal, 27(62), 15545-15553.
  Hatzfeld, Jana; Skowaisa, Steffen; Jäckel, Elisabeth; Kaufmann, Julia & Haak, Edgar