Transfer Hydrogenation of Flavanones and ortho‐Hydroxychalcones to 1,3‐Diarylpropanols Catalyzed by CNN Pincer Ruthenium Complexes

Abstract

The transfer hydrogenation of flavanones and ortho-hydroxychalcones catalyzed by ruthenium pincer complexes RuCl (CNNPh)(disphosphine) has allowed the synthesis of orthohydroxy 1,3-diarypropanols in 80-88 % yield, under mild reaction conditions and short reaction times (1 h) in 2-propanol. The amount of the co-catalyst NaOiPr has been found crucial for the selective reduction of flavanones to ortho-hydroxy 1,3diarypropanols vs. flavan-4-ols. Preliminary results show that with pincer catalysts bearing (S,R)-Josiphos, flavanone is reduced to the corresponding (S)-alcohol in moderate conversion (36 %) and up to 92 % ee.

Ru(II)-Catalyzed Asymmetric Transfer Hydrogenation of Chalcones in Water: Application to the Enantioselective Synthesis of Flavans BW683C and Tephrowatsin E

“…13 C { 1 H} NMR (126 MHz, CDCl 3 , Me 4 Si) δ 158.0, 155.6, 133.4, 129.5, 129.1, 127.5, 127.3, 119.9, 117.3, 114.0, 75.4, 55.5, 38.7, 31.1. Spectroscopic data were consistent with those reported in the literature …”

“…The solution was passed through a short pad of silica gel, which was washed with EtOAc (30 mL). The combined filtrate was then concentrated under reduced pressure, and the residue was purified by preparative TLC (EtOAc/hexane, 30:70, 100 mL) to afford (R)- 18 Synthesis of (E)-3-(5-Chloro-2-hydroxyphenyl)-1-(4chlorophenyl)prop-2-en-1-one (7a). A mixture of 4′-chloroacetophenone (2 mmol, 309 mg, 260 μL) and 5-chlorosalicilaldehyde (2 mmol, 313 mg) was dissolved in ethanol (10 mL) and stirred in an ice bath for 10 min.…”

“…Thus, the one-pot CC/CO reduction of chalcones, which are cross-conjugated α,β-unsaturated ketones, could be considered one of the most straightforward routes toward the enantioselective synthesis of 1,3-diarylpropan-1-ols. However, only a few compounds were obtained using this strategy without a thorough evaluation of the scope and stereoelectronic effects or even synthetic applications. , …”

“…However, only a few compounds were obtained using this strategy without a thorough evaluation of the scope and stereoelectronic effects or even synthetic applications. 17,18 Hence, in this work, we envisioned that a broad scope of chalcones could be enantioselectively reduced toward 1,3diarylpronan-1-ols by Noyori−Ikariya type complexes using HCO 2 Na as the hydrogen source in water. The evaluation of the electronic and steric effects in both aromatic rings over the reactivity and chemo-and enantioselectivities could provide access to 1,3-diarylpropan-1-ols and flavans through a green and practical catalytic protocol.…”