Ruthenium hydride catalyzed α-alkylation of ketones with primary alcohols for access to bioactive molecules using the borrowing hydrogen approach

Abstract

A new ruthenium hydride complex, [L1RuH(CO)(PPh3)2] (1), featuring the 2-(2H-benzo[d][1,2,3]triazol-2-yl)-4,6-di-tert-pentylphenol (L1) ligand, has been synthesized and thoroughly characterized by UV-visible, infrared, NMR, and HRMS spectroscopy. The molecular structure was confirmed by single-crystal X-ray diffraction analysis. Complex 1 demonstrated high catalytic efficiency (~70-92% yield) in the α-alkylation of ketones with primary alcohols under mild conditions using the borrowing hydrogen method. A detailed mechanistic investigation was also performed to understand the catalytic process, and the intermediate species was authenticated by HRMS spectroscopy. Effectiveness of catalyst 1 is demonstrated by enabling the synthesis of several valuable bioactive molecules, including loureirin A, loureirin B, uvangoletin, and 1-(2,4-dimethoxyphenyl)-3-(4-methoxyphenyl)-1-propanone.