Download PDF
Synlett 2007(11): 1780-1784  
DOI: 10.1055/s-2007-982570
CLUSTER
© Georg Thieme Verlag Stuttgart · New York

Gold-Catalyzed Hydroxy- and Alkoxycyclization of Functionalized Enynes

Emilie Genin, Lucie Leseurre, Patrick Yves Toullec, Jean-Pierre Genêt*, Véronique Michelet*
Laboratoire de Synthèse Sélective Organique et Produits Naturels, ENSCP UMR 7573, 11 Rue P. et M. Curie, 75231 Paris Cedex 05, France
Fax: +33(1)44071062; e-Mail: jean-pierre-genet@enscp.fr; e-Mail: veronique-michelet@enscp.fr;
Further Information

Publication History

Received 5 March 2007
Publication Date:
25 June 2007 (online)

    Permissions and Reprints All articles of this category

Abstract

A general AuIII catalytic system is described for the efficient hydroxy- and alkoxycyclization reactions of 1,6-enynes. The reactions lead to carbo- and heterocyclic alcohols or ethers in good to excellent yields. The cyclizations are conducted in the presence of AuCl3/AgSbF6/PPh3 catalyst in dioxane-water or various alcohols at room temperature. The hydroxycyclization reactions of 1,7-enynes afforded either the methyl ketone or a mixture of the methyl ketone and the carbocyclic alcohol.

Keywords

gold - cycloisomerization - enyne - atom economy - alkoxycyclization

10

A lower reactivity was observed in the presence of AuI-catalyst precursors.

11

Standard Procedure: A mixture of enyne 1 (1 equiv), and AuCl3 (10 mol%), triphenylphosphane (10 mol%), and AgSbF6 (30 mol%) was degassed and stirred at r.t. in 14% aq dioxane or in the corresponding alcohol (1.75 mL solvent/mmol of 1). The mixture was filtered through a short pad of Florisil® or silica gel (cyclohexane-EtOAc, 50:50) and the solvents were evaporated under reduced pressure. The crude product was purified if necessary by silica gel flash chromatography (cyclohexane-EtOAc, 90:10) to give the corresponding alcohol or ether.

12

Dimethyl 4-(1-Ethoxyphenylmethyl)-3-methylene-cyclopentane-1,1-dicarboxylate (2h)
R f = 0.51 (cyclohexane-EtOAc, 80:20). 1H NMR (300 MHz, CDCl3): δ = 1.13 (t, J = 7.0 Hz, 3 H), 2.31-2.44 (m, 2 H), 2.84-3.00 (m, 3 H), 3.24-3.45 (m, 2 H), 3.68 (s, 3 H), 3.74 (s, 3 H), 4.25 (d, J = 6.0 Hz, 1 H), 4.48 (br s, 1 H), 4.91 (br s, 1 H), 7.25-7.34 (m, 5 H). 13C NMR (300 MHz, CDCl3): δ = 15.2 (CH3), 35.4 (CH2), 42.1 (CH2), 49.4 (CH), 52.6 (2 CH3), 58.7 (C), 64.6 (CH2), 83.7 (CH), 108.5 (CH2), 127.2 (2 CH ar), 127.4 (CH ar), 128.1 (2 CH ar), 141.4 (C), 148.6 (C), 172.1 (C), 172.2 (C). MS (DCI/NH3): m/z = 350 [M + NH4]+, 333 [M + H]+. HRMS (DCI/CH4): m/z calcd for C19H25O3: 333.1702; found: 333.1703.
3-(1-Ethoxymethylethyl)-4-methylene- N -tosyl-pyrrolidine (2i)
R f = 0.20 (cyclohexane-EtOAc, 80:20). 1H NMR (300 MHz, CDCl3): δ = 1.00 (s, 3 H), 1.05 (t, J = 7.0 Hz, 3 H), 1.11 (s, 3 H), 2.41 (s, 3 H), 3.70-3.90 (m, 1 H), 3.24-3.41 (m, 4 H), 3.76 (br s, 2 H), 5.01-5.04 (m, 2 H), 7.31 (d, J = 8.6 Hz, 2 H), 7.69 (d, J = 8.6 Hz, 2 H). 13C NMR (300 MHz, CDCl3): δ = 15.8 (CH3), 21.5 (CH3), 22.4 (CH3), 22.8 (CH3), 49.7 (CH2), 51.1 (CH), 53.4 (CH2), 56.4 (CH2), 75.9 (C), 110.6 (CH2), 127.8 (2 CH ar), 129.6 (2 CH ar), 132.7 (C), 143.5 (C), 144.7 (C). MS (DCI/NH3): m/z = 324 [M + H]+.
Dimethyl 4-(1-Allyloxyphenylmethyl)-3-methylene-cyclopentane-1,1-dicarboxylate (2j)
R f = 0.48 (cyclohexane-EtOAc, 80:20). 1H NMR (300 MHz, CDCl3): δ = 2.30-2.55 (m, 2 H), 2.80-3.05 (m, 2 H), 3.67 (s, 3 H), 3.68-3.75 (m, 1 H), 3.74 (s, 3 H), 3.85-3.95 (m, 1 H), 4.34 (d, J = 5.9 Hz, 1 H), 4.50 (br s, 1 H), 4.92 (br s, 1 H), 5.11 (dd, J = 10.4, 1.6 Hz, 1 H), 5.20 (dd, J = 17.2, 1.6 Hz, 1 H), 5.83 (ddt, J = 17.2, 10.4, 1.7 Hz, 1 H), 7.26-7.35 (m, 5 H). 13C NMR (300 MHz, CDCl3): δ = 35.4 (CH2), 42.2 (CH2), 49.3 (CH), 52.6 (2 CH3), 58.7 (C), 69.8 (CH2), 83.1 (CH), 108.6 (CH2), 116.4 (CH2), 127.3 (2 CH ar), 127.6 (CH ar), 128.2 (2 CH ar), 134.9 (CH), 140.8 (C), 148.4 (C), 172.0 (C), 172.1 (C). MS (DCI/NH3): m/z = 362 [M + NH4]+, 345 [M + H]+. HRMS (DCI/CH4): m/z calcd for C22H29O5: 373.2015; found: 373.2025.
1,1-Bis(phenylsulfonyl)-4-(1-Allyloxymethylethyl)-3-methylenecyclopentane (2k)
R f = 0.3 (cyclohexane-EtOAc, 80:20). 1H NMR (300 MHz, CDCl3): δ = 1.14 (s, 3 H), 1.23 (s, 3 H), 2.60 (ddd, J = 15.4, 8.9, 1.6 Hz, 1 H), 2.72-2.81 (m, 1 H), 3.05 (br t, J = 8.9 Hz, 1 H), 3.48-3.55 (m, 2 H), 3.84-3.90 (m, 2 H), 4.99 (br s, 1 H), 5.04 (br s, 1 H), 5.11 (dd, J = 10.4, 1.6 Hz, 1 H), 5.26 (dd, J = 17.2, 1.6 Hz, 1 H), 5.75-6.00 (m, 1 H), 7.54-7.62 (m, 4 H), 7.68-7.71 (m, 2 H), 8.03-8.09 (m, 4 H). 13C NMR (300 MHz, CDCl3): δ = 22.6 (CH3), 23.2 (CH3), 33.5 (CH2), 40.5 (CH2), 50.7 (CH), 62.4 (CH2), 76.6 (C), 91.8 (C), 111.2 (CH2), 115.4 (CH2), 128.6 (4 CH ar), 131.0 (2 CH ar), 131.1 (2 CH ar), 134.7 (CH ar), 134.8 (CH ar), 135.5 (CH), 135.8 (C), 137.2 (C), 146.5 (C). MS (DCI/NH3): m/z = 478 [M + NH4]+. HRMS (DCI/CH4): m/z calcd for C24H32O5NS2: 478.1722; found: 478.1715.

14

Dimethyl 3-Hydroxy-4-methyl-5-methylenecyclohexane-1,1-dicarboxylate (3l H )
R f = 0.13 (cyclohexane-EtOAc, 80:20. 1H NMR (300 MHz, CDCl3): δ = 1.14 (d, J = 6.7 Hz, 3 H), 1.81 (dd, J = 13.3, 9.8 Hz, 1 H), 1.95-2.10 (m, 2 H), 2.53-2.61 (m, 2 H), 2.86 (dd, J = 13.6, 9.8 Hz, 1 H), 3.30-3.50 (m, 1 H), 3.47 (s, 3 H), 3.70 (s, 3 H), 4.82 (br s, 1 H), 4.88 (br s, 1 H). 13C NMR (300 MHz, CDCl3): δ = 14.0 (CH3), 38.6 (CH2), 39.7 (CH2), 44.6 (CH), 52.5 (CH3), 52.9 (CH3), 55.9 (C), 73.0 (CH), 111.4 (CH2), 145.0 (C), 170.7 (C), 171.6 (C). MS (DCI/NH3): m/z = 260 [M + NH4]+, 243 [M + H]+, 228 [M - MeOH + NH4]+, 211 [M - MeOH + H]+. HRMS (DCI/CH4): m/z calcd for C12H19O5: 243.1232; found: 243.1239.

Dimethyl ( E )-2-(3-Oxobutyl)-2-(3-phenylallyl)malonate (4m)
R f = 0.20 (cyclohexane-EtOAc, 80:20). 1H NMR (300 MHz, CDCl3): δ = 2.13-2.22 (m, 5 H), 2.50 (t, J = 8.2 Hz, 2 H), 2.78 (dd, J = 7.5, 1.3 Hz, 2 H), 3.74 (s, 6 H), 6.00 (dt, J = 15.5, 7.5 Hz, 1 H), 6.45 (d, J = 15.5 Hz, 1 H), 7.26-7.30 (m, 5 H). 13C NMR (300 MHz, CDCl3): δ = 26.9 (CH2), 29.9 (CH3), 37.6 (CH2), 38.7 (CH2), 52.5 (2 CH3), 57.2 (C), 123.6 (CH), 126.2 (2 CH ar), 127.5 (CH), 128.5 (2 CH ar), 134.2 (C), 136.9 (C), 171.4 (C), 207.1 (C). MS DCI/NH3: m/z = 336 [M + NH4]+, 319 [M + H]+.