Selective Monoalkylation of the Fulvene-type Enolates of 4-Alkylidene­cyclopentenones

Abstract

4-Alkylidenecyclopentenones were shown to be prone to polyalkylation because of their very easy enolization. They were ­selectively monoalkylated through the organozinc aided alkylation of their new fulvene-type enolates.

cyclopentenones - fulvene enolates - alkylations - organozinc - prostanoids

References and Notes

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Typical Experimental Procedure (Table 2, Entry 4): 5-Benzyl-2,3-diethyl-4-isopropylidene-cyclopent-2-enone ( 6ca).
To a stirred suspension of NaH (60% w/w in oil, 44 mg, 1.1 mmol) in DMF (2 mL) at 0 °C was added dropwise a solution of cyclopentenone 3c (178 mg, 1 mmol) in DMF (2 mL). After 10 min of stirring at this temperature, Me₂Zn (2 M toluene solution, 500 µL, 1 mmol) was added slowly via syringe and the mixture was stirred for 10 min. Then, benzylbromide 5a (198 mg, 1.16 mmol) in a little DMF was added rapidly. The mixture was warmed to r.t. and stirred for 4.5 h. Then, the mixture was quenched with sat. aq NH₄Cl, diluted with H₂O and extracted with Et₂O. The combined extracts were washed with brine, dried over anhyd MgSO₄, filtered, and concentrated under vacuum. Purification of crude product by flash chromatography (silica gel,
PE-Et₂O = 90:10) provided the starting cyclopentenone 3c (8 mg, 4%) and cyclopentenone 6ca (164 mg, 61%) as a yellow oil.
Compound 6ca: R _f = 0.35 (PE-Et₂O = 70:30). UV (EtOH): l_max (ε/dm³mol^-1cm^-1): 306 nm (11934). IR (thin film): n = 3080, 3060, 3020, 2960, 2920, 2870, 1685, 1580, 1490, 1450, 1380, 1360, 1285, 1245, 1190, 1130, 1110, 1080, 1060, 1050, 1045, 1030, 1020, 965, 920, 835, 820, 740, 700 cm^-1. ¹H NMR (300 MHz, CDCl₃): d = 7.09-7.07 (m, 3 H, m- and p-Ar), 6.95-6.89 (m, 2 H, o-Ar), 3.17 (dd, A of ABM, ^² J _AB = 11.8 Hz, ^³ J _AM = 3.6 Hz, 1 H, CH-Ph), 3.12 (poorly defined dd, M of ABM, ^³ J _BM = 4.7 Hz, ^³ J _AM = 3.6 Hz, 1 H, CO-CH), 3.03 (dd, B of ABM, ^² J _AB = 11.8 Hz, ^³ J _BM = 4.7 Hz, 1 H, CH-Ph), 2.46 (partly masked dq, A′ of A′B′M′, ^² J _{A ′ B ′} = 13.4 Hz, ^³ J _{A ′ M ′} = 7.6 Hz, 1 H, CHC=CCO), 2.40 (partly masked dq, B′ of A′B′M′, ^² J _{A ′ B ′} = 13.4 Hz, ^³ J _{B ′ M ′} = 7.4 Hz, 1 H, CHC=CCO), 2.11 [dq, A′′ of A′′B ′′M′′, ^² J _{A ′′ B ′′} = 13.4 Hz, ^³ J _{A ′′ M ′′} = 7.5 Hz, 1 H, CHC(=)CO], 2.02 (s, 3 H, =CCH₃), 1.99 [non-visible dq, masked by the two singlets at d = 2.02 and 1.98 ppm, B′′ of A′′B′′M′′₃, 1 H, CHC(=)CO], 1.98 (s, 3 H, =CCH₃), 0.76 (t, ^³ J = 7.5 Hz, 3 H), 0.72 (t, ^³ J = 7.5 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 208.0 (C-1, C=O), 170.0 (C-3), 144.5 (C-2), 137.3 (Cq, Ar), 133.8 (C-4), 130.2 (2 C, o-Ar), 130.1 (CqMe₂), 127.8 (2 C, m-Ar), 126.5 (1 C, p-Ar), 50.9 (C-5), 37.3 (CH₂Ph), 25.7 (CqCH₃), 22.4 (CH₂), 21.6 (CqCH₃), 16.5 (CH₂), 13.7 (CH₃), 13.6 (CH₃). MS (ESI): m/z = 291 [M + Na⁺], 269 [M + H⁺]. HRMS (EI): m/z calcd for C₁₉H₂₄O [M⁺ ]: 268.1827; found: 268.1825.

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