Iridium-Catalyzed Ligand-Controlled Semi-Reduction of Alkynes Employing H₂O as the Hydrogen Donor and Its Application

Abstract

An iridium-catalyzed ligand-controlled semi-reduction of alkynes employing H₂O as the hydrogen donor, together with its application, is reported. The use of di-tert-butylphosphinous chloride is crucial for stereoselectivity toward Z-olefins, whereas the use of 2-(diphenylphosphino)benzaldehyde is crucial for stereoselectivity toward E-olefins. More than 35 alkenes were obtained in good yields and high stereoselectivities. The utility of the current method in practical applications was investigated by studying the drug effects of (E)-1,3-dimethoxy-5-styrylbenzene on nerve growth in a zebrafish model.

Key words

iridium catalysis - ligand control - semi-reduction - alkynes - alkenes

Publication History

Received: 01 August 2023

Accepted after revision: 25 September 2023

Article published online:
02 November 2023

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• 12 (Z)-Alkenes 2; General Procedure A 15 mL pressure tube was charged with the appropriate alkyne 1 (0.1 mmol) and [Ir(cod)Cl]₂ (2.5 μmol, 1.68 mg) under a N₂ atmosphere. t-Bu₂PCl (0.02 mmol, 3.8 μL), H₂O (10 mmol, 180 μL), and THF (1.5 mL) were added, and the resultant mixture was heated at 120 °C with stirring for ~24 h under N₂. The solution was then cooled to r.t. and diluted with EtOAc (5 mL). The organic phases were washed with brine, and the aqueous phase was extracted with EtOAc. The organic phases were dried, filtered, and concentrated to give a crude product that was purified by column chromatography [silica gel, hexane or hex–EtOAc (100:1 to 40:1)]. (Z)-1,2-Diphenylethene (2a)¹³ Colorless liquid; yield: 16.2 mg (90%). ¹H NMR (400 MHz, CDCl₃): δ = 7.26–7.17 (m, 10 H), 6.60 (d, J = 1.5 Hz, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 137.4, 130.4, 129.0, 128.3, 127.2. (E)-Alkenes 3; General Procedure A 15 mL pressure tube was charged with the appropriate alkyne 1 (0.1 mmol) and [Ir(cod)Cl]₂ (2.5 μmol, 1.68 mg) under a N₂ atmosphere. DPPBde (0.02 mmol, 5.8 mg), H₂O (10 mmol, 180 μL), and THF (1.5 mL) were added, and the resultant mixture was heated at 120 °C with stirring for ~28 h under N₂; the slightly longer reaction time might be beneficial for the isomerization. The solution was then cooled to r.t. and diluted with EtOAc (5 mL). The organic phases were washed with brine, and the aqueous phase was extracted with EtOAc. The organic phases were dried, filtered, and concentrated to give a crude product that was purified by column chromatography [silica gel, hexane or hex–EtOAc (100:1 to 40:1)]. (E)-1,2-Diphenylethene (3a)¹³ White solid; yield: 15.6 mg (87%). ¹H NMR (400 MHz, CDCl₃): δ = 7.52 (d, J = 7.3 Hz, 4 H), 7.36 (t, J = 7.6 Hz, 4 H), 7.26 (dd, J = 10.0, 4.6 Hz, 2 H), 7.11 (s, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 137.5, 128.8, 127.8, 126.6.
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