Ru(II)-Catalyzed Asymmetric Transfer Hydrogenation of Chalcones in Water: Application to the Enantioselective Synthesis of Flavans BW683C and Tephrowatsin E
Felipe C. Demidoff, Guilherme S. Caleffi, Marcella Figueiredo, Paulo R. R. Costa
Abstract
The oxo-tethered-Ru(II) precatalyst promoted the one-pot C═C/C═O reduction of chalcones using sodium formate as the hydrogen source in water through asymmetric transfer hydrogenation. Twenty-seven 1,3-diarylpropan-1-ols were obtained in good to excellent yields (up to 96%) and enantiomeric purities (up to 98:2). Our data suggested that the enones are first reduced to the corresponding dihydrochalcones (1,4-selectivity) and then into 1,3-diarylpropan-1-ols (C═O reduction). The stereoelectronic effects of electron-donating and electron-withdrawing groups at the ortho, meta and para positions of both aromatic rings were evaluated. The 2-OH group at the B ring was well tolerated, allowing a straightforward enantioselective synthesis of two flavans through the Mitsunobu cyclization, the antiviral (S)-BW683C and the natural flavan (S)-tephrowatsin E.