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Exogenous Ligand-Free NiH-Catalyzed Hydroacylation of Aryl Alkenes with Aroyl Fluorides

Jihye Kim, Jieun Jang, Yoonho Lee and Kwangmin Shin*

*Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea, Email: kmshinskku.edu

J. Kim, J. Jang, Y. Lee, K. Shin, Org. Lett., 2022, 24, 5412-5416.

DOI: 10.1021/acs.orglett.2c02110



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Abstract

A nickel hydride-catalyzed hydroacylation of aryl alkenes using aroyl fluorides proceeds without recourse to an exogenous ligand under mild conditions. The synthetic utility of the present method is demonstrated by a glovebox-free, gram-scale reaction and late-stage derivatizations of complex molecules.

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The document discusses a study on nickel hydride (NiH)-catalyzed hydroacylation of aryl alkenes using aroyl fluorides, conducted by Jihye Kim, Jieun Jang, Yoonho Lee, and Kwangmin Shin. This method is notable for its exogenous ligand-free conditions and mild reaction environment. The research highlights the efficiency of acyl fluorides as acyl group donors, which have been underutilized in transition-metal-catalyzed hydroacylation. The optimized reaction conditions involve using NiCl2·DME as the catalyst, K3PO4 as the base, and (EtO)3SiH as the hydride source, achieving high yields of α-aryl ketone products. The study demonstrates the method's synthetic utility through gram-scale reactions and late-stage derivatization of complex molecules. Mechanistic studies suggest that the hydronickelation step is irreversible, and the unique reactivity of aroyl fluorides is superior to other acyl electrophiles. The research aims to develop an asymmetric variant and further investigate the reaction mechanism. The work is supported by the National Research Foundation of Korea and the POSCO TJ Park Foundation.


General Procedures for Hydroacylation of Aryl Alkenes with Aroyl Fluorides

In an argon-filled glovebox, an oven-dried screw-cap reaction tube equipped with a magnetic stir bar was charged with NiCl2•DME (6.6 mg, 0.03 mmol, 15 mol%) and K3PO4 (127.4 mg, 0.60 mmol, 3.0 equiv). DMF solvent (1.6 mL) was added via syringe and the resulting mixture was stirred for 10 min. (EtO)3SiH (40 µL, 0.22 mmol, 1.1 equiv) was added via micropipette and the reaction mixture was further stirred for 5 min before the addition of aryl alkene (0.20 mmol, 1.0 equiv) and aroyl fluoride (0.30 mmol, 1.5 equiv). Then, the remaining DMF solvent (0.4 mL) was added while rinsing the wall of the reaction tube. The reaction vessel was sealed with a screw cap, removed from the glovebox, and allowed to stir at room temperature for 24 h. After this time, saturated aqueous NaHCO3 solution (ca. 5 mL) was added to quench the reaction. Then the aqueous layer was extracted with Et2O (ca. 5 mL x 3). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure. The crude reaction mixture was purified by silica column chromatography or preparative TLC on silica gel to obtain the desired hydroacylation product.


Key Words

hydroacylation, triethoxysilane


ID: J54-Y2022