C-C Coupling through Nitrogen Deletion: Application to Library Synthesis

Serhii Holovach; Kostiantyn P Melnykov; Illia Poroshyn; Rustam T Iminov; Dmytro Dudenko; Ivan Kondratov; Mark Levin; Oleksandr O Grygorenko

doi:10.1002/chem.202203470

C-C Coupling through Nitrogen Deletion: Application to Library Synthesis

Chemistry. 2023 Jan 18;29(4):e202203470. doi: 10.1002/chem.202203470. Epub 2022 Dec 21.

Authors

Serhii Holovach¹, Kostiantyn P Melnykov^{1

2}, Illia Poroshyn¹, Rustam T Iminov¹, Dmytro Dudenko^{1

3}, Ivan Kondratov^{1

4}, Mark Levin⁵, Oleksandr O Grygorenko^{1

2}

Affiliations

¹ Enamine Ltd., Chervonotkatska Street 78, Kyiv, 02094, Ukraine.
² Taras Shevchenko National University of Kyiv, Volodymyrska Street 60, Kyiv, 01601, Ukraine.
³ Chemspace, Chervonotkatska Street 85, Kyiv, 02094, Ukraine.
⁴ V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Akademik Kukhar Street 1, Kyiv, 02094, Ukraine.
⁵ Department of Chemistry, University of Chicago, 5735 S Ellis Ave, Chicago, IL 60637, USA.

PMID: 36445790
DOI: 10.1002/chem.202203470

Abstract

A protocol for parallel C(sp³ )-C(sp³ ) coupling of (hetero)aromatic aldehydes and (hetero)arylmethyl amines based on a reductive amination - "nitrogen deletion" reaction sequence has been developed. After preliminary validation experiments, an illustrative compound library of 25 members was prepared with 76 % synthetic efficiency. The estimated chemical space accessible by the proposed approach covers almost 600 000 representatives that are scarcely represented in current compound databases.

Keywords: combinatorial chemistry; heterocycles; lead-likeness; parallel synthesis; skeletal editing.

Abstract

Grants and funding