Synthesis of Substituted Cyclopentenol Derivatives via Intramolecular Addition Reaction of Vinylcopper Species

Abstract

A new method for the synthesis of substituted cyclopentenes is developed, based on an intramolecular 1,2-addition reaction of vinylcopper species generated from 1,1-dibromoalkene derivatives. The substrates are prepared from ketones through the aldol reaction with 3,3-dibromoacrolein followed by silylation of the hydroxyl group. Treatment of the substrate with excess Me₂CuLi results in the formation of 3-methyl-2-cyclopenten-1-ol derivatives with good yields.

Key words

annulation reactions - ketones - 1,1-dibromoalkenes - ­Gilman reagents - cyclopentenes

• References and Notes


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• 13 General Procedure (Table 2, Entry 1) To a cooled (–78 °C) suspension of CuI (609 mg, 3.20 mmol) in ether (6.4 mL) was added dropwise a 1.17 M ethereal solution of MeLi (5.47 mL, 6.40 mmol). The mixture was warmed up to 0 °C and stirred for 10 min. The resulting clear solution was cooled to –78 °C, and a 1.5:1 diastereomeric mixture of ketone 13b (264 mg, 0.640 mmol) in ether (6.4 mL) was added. The mixture was warmed up to 0 °C immediately and stirred for 10 min at the temperature. The reaction was quenched with a saturated aqueous NH₄Cl solution. The mixture was filtered through a short pad of Celite, and the aqueous layer was extracted with ether. Concentration in vacuo and purification by silica gel column chromatography afforded a 2:1 diastereomeric mixture of cyclopentenol 14b (136 mg, 0.50 mmol, 79%) as a yellow oil. ¹H NMR (500 MHz CDCl₃): δ = 5.36 (0.5 H, s), 5.33 (1 H, s), 4.86 (1 H, dt, J = 7.4, 1.7 Hz), 4.14 (0.5 H, d, J = 1.1 Hz), 2.41 (1 H, td, J = 8.3, 4.6 Hz), 2.16 (0.5 H, t, J = 4.6 Hz), 2.03 (1 H, dt, J = 10.7, 3.6 Hz), 1.90–1.80 (3 H, m), 1.74 (1 H, t, J = 1.4 Hz), 1.72 (3 H, dd, J = 4.9, 3.7 Hz), 1.70–1.47 (3 H, m), 0.88 (13.5 H, m), 0.07 (3 H, t, J = 3.2 Hz), 0.05 (6 H, s). ¹³C NMR (125 MHz, CDCl₃): δ = 146.23, 144.46, 131.3, 129.61, 95.6, 93.69, 81.98, 74.89, 61.04, 54.82, 38.28, 36.55, 31.63, 26.52, 26.40, 25.98, 25.93, 25.63, 25.46, 18.33, 11.95, 11.54, –4.50, –4.58, –4.74, –4.91.