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Synlett 2006(5): 0681-0684  
DOI: 10.1055/s-2006-933106
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

Stéphane Laurent, Nasima Chorfa, Mohammed Ahmar, Bernard Cazes*
Université Claude Bernard - LYON 1, UMR-CNRS 5181, Laboratoire de Chimie Organique 1, Bât. CPE-Lyon, 43 Bd. du 11 Novembre 1918, 69622 Villeurbanne, France
Fax: +33(4)72431214; e-Mail: cazes@univ-lyon1.fr;
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Publication History

Received 10 November 2005
Publication Date:
09 March 2006 (online)

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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.

Key words

cyclopentenones - fulvene enolates - alkylations - organozinc - prostanoids

15

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): lmax (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.