Regioselective 1,2-Dearomatization of Functionalized Azines by Organolanthanide Catalysts

NU2014-129

INVENTORS

  • Tobin Marks*
  • Alexander Dudnik
  • Massimiliano Delferro
  • Victoria Weidner

SHORT DESCRIPTION
This invention describes a catalytic process for the regioselective 1,2-dearomatization of functionalized azines using an organolanthanide catalyst and pinacolborane (HBpin). It offers a streamlined approach to key intermediates for pharmaceuticals and natural products.

BACKGROUND
For decades, precious metal‐based catalysts have dominated organic synthesis, enabling rapid production of pharmaceuticals, natural products, and advanced materials. However, existing dearomatization methods often require harsh reaction conditions and lack selectivity, limiting their efficiency. This invention addresses these challenges by providing an efficient, selective method for the dearomatization of six-membered nitrogen-containing heterocycles, which are critical components in many essential medicines.

ABSTRACT
This technology presents a general catalytic approach to achieve regioselective 1,2-dearomatization of functionalized azines using an earth-abundant organolanthanide catalyst in combination with pinacolborane (HBpin). Detailed kinetic studies and computational analyses elucidate the reaction mechanism, establishing the method’s precision and efficiency for preparing valuable synthetic intermediates. The process is designed to meet the needs of commercial synthesis of complex nitrogen-containing compounds, offering robust performance under mild conditions while significantly improving reaction selectivity.

APPLICATIONS

  • Building blocks for synthesis of pharmaceuticals and natural products

ADVANTAGES

  • Achieves 100% regioselectivity in 1,2-dearomatization compared to previous catalytic methods

PUBLICATIONS
Tobin Marks et al., Atom-Efficient Regioselective 1,2-Dearomatization of Functionalized Pyridines by an Earth-Abundant Organolanthanide Catalyst, Nature Chemistry

IP STATUS
Issued US Patent US20160159825A1

Patent Information: