Chelation-Assisted Rhodium-Catalyzed Alkylation of a 1-Arylpyrazole C–H Bond with Cyclopropanols

Abstract

A general and efficient rhodium-catalyzed ortho-alkylation of N-arylpyrazoles has been accomplished with cyclopropanols as coupling partners. The reaction involves cleavage of both a C–H bond of the arene and a C–C bond of the cyclopropanol, and it offers access to a diversity of substituted 1-(ortho-alkylaryl)-1H-pyrazoles in good to excellent yields. In addition, nonsymmetrical dialkylation and a preliminary mechanistic investigation are also discussed.

Key words

alkylation - cyclopropanols - C–H bond functionalization - rhodium catalysis - arylpyrazoles

Publication History

Received: 20 July 2022

Accepted after revision: 02 November 2022

Accepted Manuscript online:
02 November 2022

Article published online:
23 December 2022

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• 13 1-Phenyl-3-[2-(1H-pyrazol-1-yl)phenyl]propan-1-one (3aa); Typical Procedure An oven-dried pressure tube was charged with pyrazole 1a (3.5 mmol, 1.0 equiv), cyclopropanol (2a; 10.5 mmol, 3.0 equiv), [Cp*RhCl₂]₂ (107 mg, 5.0 mol%), AgSbF₆ (121 mg, 10 mol%), and Cu(OAc)₂·H₂O (697 mg, 1 equiv) under argon. Anhyd MeOH (20 mL) was added to the mixture, and the pressure tube was sealed and kept in a preheated oil bath at 100 °C for 24 h. When the reaction was complete, the mixture was cooled to r.t., diluted with CH₂Cl₂, and filtered through a small pad of Celite. The solvent was removed under reduced pressure and the resulting crude product was purified by column chromatography [silica gel, EtOAc–hexane (1:9)] to give a yellow liquid; yield: 84%; R_f = 0.50 (EtOAc–hexane, 1:9). IR (Neat): 2941, 2934, 1681, 1513, 1204, 1049, 775 cm^–1. ¹H NMR (400 MHz, CDCl₃, 24 °C): δ = 7.87 (d, J = 7.8 Hz, 2 H), 7.70 (s, 1 H), 7.63 (s, 1 H), 7.51 (t, J = 7.8 Hz, 1 H), 7.44–7.33 (m, 4 H), 7.28 (d, J = 4.6 Hz, 2 H), 6.43 (s, 1 H), 3.14 (t, J = 8.6 Hz, 2 H), 2.98 (t, J = 8.6 Hz, 2 H). ¹³C{¹H} NMR (100 MHz, CDCl₃, 24 °C): δ = 199.3, 140.5, 139.8, 137.5, 136.7, 133.1, 130.8, 128.9, 128.5, 128.1, 127.1, 126.6, 106.6, 39.8, 26.6. HRMS (ESI/Q-TOF): m/z: [M + Na]⁺ calcd for C₁₈H₁₆N₂NaO: 299.1155; found: 299.1158.