Cooperative Catalysis System for Enantioselective Transformations of Oxocarbenium Ions

NU 2019-063

INVENTORS

• Karl Scheidt*
• Mark Andrew Maskeri

SHORT DESCRIPTION

This invention introduces a cooperative catalysis system that enhances the reactivity and selectivity of oxocarbenium ions, facilitating new enantioselective transformations and enabling the synthesis of pharmacologically active tetrahydropyranoindole compounds.

BACKGROUND 

Oxocarbenium ions are crucial intermediates in chemical transformations but pose challenges in asymmetric catalysis due to their weak binding capabilities with traditional catalysts. Current methods rely on electrostatic pairing, limiting their effectiveness. This invention addresses these limitations by employing a cooperative catalysis system, combining an achiral hydrogen bond donor with a chiral Brønsted acid, to achieve high selectivity and reactivity in transformations involving oxocarbenium ions.

ABSTRACT

The cooperative catalysis system presented here offers a groundbreaking approach to the enantioselective transformation of oxocarbenium ions, overcoming the limitations of traditional methods. By integrating an achiral hydrogen bond donor with a chiral Brønsted acid, this system facilitates highly selective and rapid oxa-Pictet–Spengler reactions. This methodology provides access to tetrahydropyranoindole compounds, which can be further developed into spirooxindole natural products with potential pharmacological applications. The invention represents a significant advancement in cooperative catalysis, enabling new and selective asymmetric transformations.

APPLICATIONS

• Synthesis of tetrahydropyranoindole compounds
  • Enables the creation of compounds with potential anti-inflammatory and analgesic properties.
• Pharmaceutical development
  • Facilitates the production of drugs targeting pain, swelling, and joint stiffness.
• Cancer treatment
  • Supports the development of compounds with potential anti-cancer activities.

• Enhanced reactivity and selectivity
  • Provides greater control over chemical transformations involving oxocarbenium ions.
• Novel cooperative catalysis
  • Combines achiral hydrogen bond donors with chiral Brønsted acids for improved outcomes.
• Versatile synthesis
  • Allows for the creation of diverse pharmacologically active compounds.

PUBLICATIONS

Mark A. Maskeri, Dr. Matthew J. O'Connor, Ashley A. Jaworski, Anna V. Bay, Karl A. Scheidt, "A Cooperative Hydrogen Bond Donor–Brønsted Acid System for the Enantioselective Synthesis of Tetrahydropyrans" Angewandte Chemie, 31 October 2018.

IP STATUS

Issued US Patent 11,479,558