Magnesiation of Alkyl Fluorides Catalyzed by Rhodium–Aluminum Bimetallic Complexes

Abstract

Since the pioneering work by Grignard in 1900, organomagnesium reagents, the so-called Grignard reagents, have been indispensable in organic synthesis. Alkyl Grignard reagents are usually prepared from the corresponding alkyl iodides, bromides, or chlorides with Mg, whereas alkyl fluorides are not viable substrates under conventional conditions due to the high stability of the C–F bonds. We report that Al–Rh bimetallic complexes catalyze the magnesiation of C(sp³)–F bonds of alkyl fluorides using easy-to-handle Mg powder. The present conditions can accommodate primary, secondary, or tertiary alkyl fluorides to afford the corresponding alkylmagnesium reagents, which can be successfully converted into various functionalities.

Key words

alkyl fluorides - organomagnesium compounds - Grignard reagents - aluminum catalysis - rhodium catalysis - C–F bond activation

• References and Notes

• 1 Present address: I. Fujii, Division of Chemistry, Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531, Japan.
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• 15 2-Methyl-4-phenylbutanoic Acid (3b); Typical Procedure In a glove box, a 4 mL vial equipped with a stirrer bar was charged with Mg powder (61 mg, 2.5 mmol, 5.0 equiv) and (3-fluorobutyl)benzene (2b; 76 mg, 0.50 mmol, 1.0 equiv). A suspension of catalyst 1a (20 mg, 13 μmol, 5.0 mol% of Rh) in THF (1.5 mL) was added to the vial, which was then capped with a PTFE sealing screw cap and removed from the glovebox. The mixture was stirred at 80 °C for 48 h, and the resulting mixture was then stirred under CO₂ at atmospheric pressure and r.t. for 2 h. 3 M aq HCl (1.5 mL) was added, and the resulting mixture was extracted with EtOAc (3 × 2.0 mL). All volatiles were removed in vacuo, and the residue was purified by MPLC [silica gel, hexane–EtOAc (70:30) + AcOH (10 vol%)] to give a colorless oil; yield: 65 mg (73%); R_f = 0.44 (hexane–EtOAc, 70:30 + 10% HOAc). ¹H NMR (400 MHz, CDCl₃): δ = 7.33–7.27 (m, 2 H), 7.23–7.14 (m, 3 H), 2.68 (t, J = 8.0 Hz, 2 H), 2.52 (sext, J = 6.9 Hz, 1 H), 2.14–1.99 (m, 1 H), 1.76 (ddt, J = 13.9, 8.4, 6.8 Hz, 1 H), 1.24 (d, J = 6.9 Hz, 3 H). ¹³C{¹H} NMR (101 MHz, CDCl₃): δ = 183.0, 141.6, 128.6, 128.5, 126.1, 38.9, 35.3, 33.5, 17.1.