Activating Methanol for Chemoselective Transfer Hydrogenation of Chalcones Using an SNS-Ruthenium Complex

Abstract

Methanol is gaining popularity as a transfer-hydrogenating agent in catalytic reduction reactions because of its bulk-scale production and inexpensive nature. Current research interests include the utilization of methanol as a safe and sustainable hydrogen source for chemical synthesis and drug development. In particular, the chemoselective reduction of α,β-unsaturated ketones is of great interest because of their prevalence in many natural products. We investigated the potential application of acridine-derived SNS-Ru pincer complexes in methanol activation for chemoselective reduction of chalcones. Our developed catalytic system showed broad substrate tolerance, including substrates containing reducible functional groups. Control experiments and postsynthetic applications are also highlighted.

Key words

ligands - ruthenium catalysis - methanol activation - chalcones - reduction - chemoselectivity

Publication History

Received: 27 June 2024

Accepted after revision: 12 August 2024

Accepted Manuscript online:
12 August 2024

Article published online:
09 September 2024

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• 30 Transfer Hydrogenation of α,β-Unsaturated Carbonyl Compounds; General Procedure A 30 mL oven-dried pressure tube containing a magnetic stirrer bar was charged with the appropriate chalcone (0.5 mmol), KOH (0.5 mmol), and catalyst Ru-1 (2 mol %). MeOH (0.2 mL) and toluene (2 mL) were then added and the tube was sealed under argon and placed in a preheated oil bath at 120 °C for 12 h. On completion of the reaction, the tube was cooled to r.t. and the crude mixture was filtered through a small plug of Celite. The solvent was evaporated and the product was purified by column chromatography (silica gel, EtOAc–hexane). 1,3-Bis(4-methoxyphenyl)propan-1-one (5a) Purified by column chromatography [silica gel (100–200 mesh), EtOAc–hexane (15:85)] to give a white solid; yield: 108 mg (80%). ¹H NMR (400 MHz, CDCl₃): δ = 7.86 (d, J = 9.0 Hz, 2 H), 7.09 (d, J = 8.8 Hz, 2 H), 6.85 (d, J = 8.9 Hz, 2 H), 6.76 (d, J = 8.6 Hz, 2 H), 3.79 (s, 3 H), 3.71 (s, 3 H), 3.14 (t, J = 7.7 Hz, 2 H), 2.92 (t, J = 8.0 Hz, 2 H). ¹³C NMR (150 MHz, CDCl₃): δ = 198.2, 163.6, 158.2, 133.7, 130.5, 130.2, 129.6, 114.1, 113.9, 55.7, 55.5, 40.6, 29.7.