Synthesis of Five- and Six-Membered-Ring Compounds by Environmentally Friendly Radical Cyclizations Using Kolbe Electrolysis

Abstract

Substituted carbocycles, tetrahydrofurans, and tetrahydropyrans can be efficiently obtained from ω-unsaturated carboxylic acids. Our methodology involves a Kolbe decarboxylation followed by an intramolecular radical cyclization and a radical-­radical cross-coupling process.

Key words

cyclization - electron transfer - green chemistry - heterocycles - radical reactions

References and Notes

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16

Representative Procedure for the Electrochemical Synthesis of Carbocycles and Heterocycles
In an undivided beaker-type cell (100 mL) bearing two electrodes of platinum foil (1.3 cm × 1.3 cm × 0.5 mm), acid 22a (500 mg, 2.47 mmol) and a fivefold excess of AcOH (707 mL, 12.38 mmol) were dissolved in MeOH (50 mL). The acids were partially neutralized by NaOMe to obtain a current density of 100 mA/cm^². The reaction was monitored by TLC or GC and stopped when the pH of the solution changed from 5 to 8; normally 1.2-1.4 F/mol had been consumed. The reaction mixture was then concentrated under reduced pressure. The residue was treated with a sat. aq solution of NaHCO₃, and extracted with CH₂Cl₂ (3 × 10 mL). The organic layers were collected, dried on Na₂SO₄, and concentrated under reduced pressure. The crude material was purified by flash chromatography (PE-Et₂O, 4:1) to afford 366 mg of compound 23a (86%, mixture of two inseparable diastereomers, A/B = 1:1) as a colorless liquid smelling of fruit. GC [60 ˚C (3 min), 15 ˚C/min → 290 ˚C, 290 ˚C (1 min)]: t _R = 10.90, 11.02 min. IR (neat): 647, 732, 915, 1047, 1076, 1179, 1262, 1377, 1459, 1725, 2873, 2978. ^¹H NMR (300 MHz, CDCl₃): δ = 1.15 (d, 3 H, A, J = 6.6 Hz), 1.20 (d, 3 H, B, J = 6.6 Hz), 1.24 (t, 3 H, A, J = 7.2 Hz), 1.26 (t, 3 H, B, J = 7.2 Hz), 1.50-1.65 (m, 1 H, A + B), 1.95-2.20 (m, 1 H, A + B), 2.25-2.55 (m, 2 H, A + B), 3.40-3.46 (dt, 1 H, A + B, J = 7.8, 2.2 Hz), 3.60-3.95 (m, 3 H, A + B), 4.08-4.18 (m, 2 H, A + B). ^¹³C NMR (75 MHz, CDCl₃): δ = 14.20 (A), 14.23 (B), 16.1 (A), 16.2 (B), 30.3 (B), 30.8 (A), 42.39 (A), 42.41 (B), 42.90 (B), 42.93 (A), 60.4 (A + B), 68.0 (A), 68.1 (B), 71.1 (A), 71.9 (B), 175.7 (A + B). MS (APCI): m/z (%) = 82.9 (15), 126.9 (95), 144.9 (15), 173.0(10). HRMS (sodium complex): m/z calcd: 195.0997; found: 195.0998.

17

Compound 27 originates from a possible rearrangement of either the primary radical or the derived carbocation. Studies are currently ongoing to elucidate this intriguing transformation.