Modular approach to 1,2-disubstituted adamantane derivatives by directed C-H functionalization reactions

• Applicant: Privatdozent Dr. Radim Hrdina
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 315058126

• Final Report Year: 2021

Final Report Abstract

We were able to contribute to the field of organometallic chemistry associated with the reactivity of adamantane and other bridged cycloalkanes. The main goal, specifically modular functionalization of adamantane derivatives, was achieved. We have found general way to 1,2-disubstituted adamantane based amines using insertion reaction of nitrenes and 1,2-disubstituted adamantane based carboxylic acids using palladium catalyzed C-H activations. New derivatives, prepared according to our protocol, can be and are now used as precursors for the synthesis of bioactive compounds, ligands of transition metals, organocatalysts or can be used as building blocks for other academical and industrial applications. The most important outcome of our work is discovery of two new transformations, i.e. cascade reaction leading to azaheterocycles with annulated adamantane scaffold and cascade reaction leading to noradamantane derivatives. Both reactions expand family of similar 1,2-alkyl shift- based transformations as Wagner-Meerwein-, Meinwald-, Demjanov-Tiffeneau- or (semi-)-pinacolrearrangement.

Publications

• Triflic Acid Promoted Decarboxylation of Adamantane-oxazolidine-2-one: Access to Chiral Amines and Heterocycles; J. Org. Chem. 2017, 82, 4891
  Hrdina, R.; Larrosa, M.; Logemann, C.
  (See online at https://doi.org/10.1021/acs.joc.7b00711)
• Directed C–H Bond Oxidation of Bridged Cycloalkanes Catalyzed by Palladium(II) Acetate; Chem. Eur. J. 2018, 24, 6269
  Larrosa, M.; Zonker, B.; Volkmann, J.; Wech, F.; Logemann, C.
  (See online at https://doi.org/10.1002/chem.201800550)
• Directed C–H Functionalization of the Adamantane Framework. Synthesis 2019, 51, 629
  Hrdina, R.
  (See online at https://doi.org/10.1055/s-0037-1610321)
• [1,2]-Rearrangement of iminium salts provides access to heterocycles with adamantane scaffold; Org. Biomol. Chem. 2020, 18, 4941
  Zonker, B.; Duman, E.; Hausmann, H.; Becker, J.; Hrdina, R.
  (See online at https://doi.org/10.1039/D0OB01156H)
• Overview of Dirhodium(II,II) Paddlewheel Complexes. Eur. J. Inorg. Chem. 2021, 501
  Hrdina, R.
  (See online at https://doi.org/10.1002/ejic.202000955)