Synthesis of γ-Aryl Medium-Sized Cyclic Enones by a Domino 4π-Electrocyclic Reaction/Heck–Matsuda Arylation Sequence at Ambient Temperature

Abstract

Bicyclo[n.2.0]cyclobutenes were transformed into medium-sized cyclic γ-aryl enones by using a cationic aryl palladium(II) species generated from a diazonium salt. The reaction proceeded at ambient temperature by capturing the cis,trans-cycloalkadiene intermediate generated through a conrotatory 4π-electrocyclic ring-opening reaction, followed by a Heck–Matsuda arylation sequence. Optically pure γ-aryl enones were also synthesized by using a point-to-planar-to-point chirality-transfer process.

Key words

medium-sized rings - electrocyclic reaction - Heck–Matsuda reaction - arylation - cyclobutenes - chirality transfer

Publication History

Received: 09 January 2023

Accepted after revision: 01 February 2023

Accepted Manuscript online:
01 February 2023

Article published online:
02 March 2023

• References and Notes

• 1 Current address: School of Pharmacy, Hyogo University of Health Sciences, Kobe 650–8530, Japan.

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• 17 γ-Arylcyclooctenones 5; General Procedure (Conditions A) A test tube was charged with Pd(OAc)₂ (0.014 mmol) together with the appropriate diazonium tetrafluoroborate 6 (0.41 mmol) and cyclobutene 1 (0.27 mmol). Ag₂CO₃ (0.54 mmol) and MeCN (0.20 M) were added to the mixture under argon, and the resulting slurry was vigorously stirred for 38 h. Et₂O was added to the mixture, which was then stirred for a further 15 min. The resulting slurry was filtered through Celite, and the filter cake was washed with Et₂O. The filtrate was concentrated under reduced pressure to remove the solvent and the residue was dissolved in Et₂O. Silica gel was added to the solution and the mixture was stirred for 30 min. The slurry was then filtered and the filter cake was washed with Et₂O. Concentration of the filtrate gave a crude product that was dissolved in CHCl₃ and purified by column chromatography (silica gel, hexane–EtOAc or hexane–EtOAc). Methyl 3-(4-Methylphenyl)-8-oxocyclooct-1-ene-1-carboxylate (5aa) Colorless oil; yield: 67 mg (90%). R_f = 0.38 (hexane–Et₂O, 4:1). IR (ATR): 2928, 2855, 1724, 1697, 1636, 1512, 1454, 1435, 1254, 1223, 1107, 1065 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.19 (d, J = 5.2 Hz, 1 H), 7.11 (d, J = 7.9 Hz, 2 H), 7.02 (d, J = 11.0 Hz, 2 H), 3.74 (s, 3 H), 3.49 (ddd, J = 10.7, 2.4, 2.4 Hz, 1 H), 2.67 (ddd, J = 16.0, 3.3, 3.3 Hz, 1 H), 2.58 (ddd, J = 14.0, 11.0, 3.0 Hz, 1 H), 2.31 (s, 3 H), 2.10–1.97 (m, 1 H), 1.97–1.86 (m, 2 H), 1.86–1.77 (m, 1 H), 1.77–1.62 (m, 2 H). ¹³C NMR (126 MHz, CDCl₃): δ = 209.2, 164.4, 147.9, 139.4, 136.5, 130.5, 129.4, 127.5, 52.3, 46.9, 44.0, 30.7, 27.9, 22.1, 20.9. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₂₁O₃: 273.1485; found: 273.1484.