Gold-Catalyzed Hydroxy- and Alkoxycyclization of Functionalized Enynes

Abstract

A general Au^III 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.

gold - cycloisomerization - enyne - atom economy - alkoxycyclization

References and Notes

For representative examples and seminal references, see:

1a Hashmi ASH. Hutchings GJ. Angew. Chem. Int. Ed.  2006,  45:  7896 

1b Jimenez-Nunez E. Echavarren AM. Chem. Commun.  2007,  333 

1c Zhang L. Sun J. Kozmin SA. Adv. Synth. Catal.  2006,  348:  2271 

1d Ma S. Yu S. Gu Z. Angew. Chem. Int. Ed.  2006,  45:  200 

1e Hashmi ASK. Angew. Chem. Int. Ed.  2005,  44:  6090 

1f Hoffmann-Röder A. Krause N. Org. Biomol. Chem.  2005,  3:  387 

1g Hashmi ASK. Gold Bull.  2004,  37:  51 

1h Pyykkö P. Angew. Chem. Int. Ed.  2004,  43:  4412 

1i Arcadi A. Di Giuseppe S. Curr. Org. Chem.  2004,  8:  795 

1j Bianchi G. Arcadi A. In Targets in Heterocyclic Systems  2004,  8:  82 

1k Dyker G. Angew. Chem. Int. Ed.  2000,  39:  4237 

2a Nevado C. Charruault L. Michelet V. Nieto-Oberhuber C. Muñoz MP. Méndez M. Rager M.-N. Genêt J.-P. Echavarren AM. Eur. J. Org. Chem.  2003,  706 

2b Charruault L. Michelet V. Genêt J.-P. Tetrahedron Lett.  2002,  43:  4757 

2c Galland J.-C. Savignac M. Genêt J.-P. Tetrahedron Lett.  1997,  38:  8695 

3a Nevado C. Cárdenas DJ. Echavarren AM. Chem. Eur. J.  2003,  9:  2627 

3b Martín-Matute B. Nevado C. Cárdenas DJ. Echavarren AM. J. Am. Chem. Soc.  2003,  125:  5757 

3c Méndez M. Muñoz MP. Nevado C. Cárdenas DJ. Echavarren AM. J. Am. Chem. Soc.  2001,  123:  10511 

3d Méndez M. Muñoz MP. Echavarren AM. J. Am. Chem. Soc.  2000,  122:  11549 

4a Charruault L. Michelet V. Taras R. Gladiali S. Genêt J.-P. Chem. Commun.  2004,  850 

4b Michelet V. Charruault L. Gladiali S. Genêt J.-P. Pure Appl. Chem.  2006,  78:  397 

5a Nishizawa M. Yadav VK. Skwarczynski M. Takao H. Imagawa H. Sugihara T. Org. Lett.  2003,  5:  1609 

5b Nishizawa M. Imagawa H. J. Synth. Org. Chem. Jpn.  2006,  64:  744 

6 Faller JW. Fontaine PP. J. Organomet. Chem.  2006,  691:  1912 

7a Muñoz MP. Adrio J. Carretero JC. Echavarren AM. Organometallics  2005,  24:  1293 

7b Nieto-Oberhuber C. Lopez S. Echavarren AM. J. Am. Chem. Soc.  2005,  127:  6178 

7c Nieto-Oberhuber C. Muñoz MP. Nevado C. Cárdenas DJ. Echavarren AM. Angew. Chem. Int. Ed.  2004,  43:  2402 

7d Mézailles N. Ricard L. Gagosz F. Org. Lett.  2005,  7:  4133 

7e Nieto-Oberhuber C. Muñoz MP. Lopez S. Jimenez-Nuñez E. Nevado C. Herrero-Gomez E. Raducan M. Echavarren AM. Chem. Eur. J.  2006,  12:  1677 

7f Buzas AK. Istrate FM. Gagosz F. Angew. Chem. Int. Ed.  2007,  46:  1141 

For recent intramolecular versions, see:

8a Zhang L. Kozmin SA. J. Am. Chem. Soc.  2005,  127:  6962 

8b

See ref. 7e.

9a Toullec P.-Y. Genin E. Leseurre L. Genêt J.-P. Michelet V. Angew. Chem. Int. Ed.  2006,  45:  7427 

9b Genin E. Toullec PY. Antoniotti S. Brancour C. Genêt J.-P. Michelet V. J. Am. Chem. Soc.  2006,  128:  3112 

9c Genin E. Antoniotti S. Michelet V. Genêt J.-P. Angew. Chem. Int. Ed.  2005,  44:  4949 

9d Antoniotti S. Genin E. Michelet V. Genêt J.-P. J. Am. Chem. Soc.  2005,  127:  9976 

10

A lower reactivity was observed in the presence of Au^I-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.

13 Nieto-Oberhuber C. Lopez S. Jimenez-Nunez E. Echavarren AM. Chem. Eur. J.  2006,  12:  5916 

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]⁺.

15a Schneider SK. Herrmann WA. Herdtweck E. Z. Anorg. Allg. Chem.  2003,  629:  2363 

15b Mizushima E. Sato K. Hayashi T. Tanaka M. Angew. Chem. Int. Ed.  2002,  41:  4563 

15c Fukuda Y. Utimoto K. J. Org. Chem.  1991,  56:  3729