Synlett 2007(1): 0063-0066  
DOI: 10.1055/s-2006-956497
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Gold(III)-Catalyzed Double Wacker-Type Reaction of 1,1-Diethynyl Acetate

Keisuke Kato*a, Ryuhei Teraguchia, Taichi Kusakabea, Satoshi Motodatea, Shigeo Yamamuraa, Tomoyuki Mochidab, Hiroyuki Akita*a
a Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
b Department of Chemistry, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
Fax: +81(474)721825; e-Mail: kkk@phar.toho-u.ac.jp;
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Publikationsverlauf

Received 5 October 2006
Publikationsdatum:
20. Dezember 2006 (online)

Abstract

Treatment of 1,1-diethynyl acetates in the presence of Au or Pt catalyst (5 mol%) in methanol at 60 °C for 20-48 hours gave γ-ketoesters and lactones in 40-54% and 19-39% yields, ­respectively. An oxygen atom is introduced to the first acetylene moiety in accordance with Markovnikov’s rule, and to the second acetylene moiety with anti-Markovnikov regioselectivity.

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Preparation of Substrates 2; General Procedure: To a solution of trimethylsilyl acetylene (3.32 g, 33.8 mmol) in THF (30 mL) under Ar was added n-BuLi (13.0 mL of 2.6 M in hexane, 33.8 mmol) at -78 °C and the mixture was stirred for 0.5 h at 0 °C. After the solution was cooled to -78 °C, the corresponding ester 1 (11.3 mmol) in THF (3 × 8 mL) was slowly added dropwise. The mixture was stirred at -10 °C for 12 h and quenched with H2O (80 mL) and EtOAc (80 mL). The organic layers were separated, the aqueous layer was extracted with EtOAc (50 mL), and combined organic layers were dried with MgSO4 and concentrated in vacuo. To a solution of the crude product in THF (30 mL) was added TBAF (22.4 mL of 1 M in THF, 22.4 mmol) and the mixture was stirred for 0.5 h at r.t. The mixture was diluted with H2O (80 mL) and EtOAc (80 mL). The organic layers were separated, the aqueous layer was extracted with EtOAc (2 × 50 mL), and combined organic layers were dried with MgSO4 and concentrated in vacuo. To a solution of the crude product in pyridine (3 mL) and Ac2O (2 mL) was added 4-dimethylaminopyridine (50 mg) and the mixture was stirred for 3-10 h at r.t. The mixture was diluted with H2O (50 mL) and EtOAc (50 mL). The organic layers were separated, the aqueous layer was extracted with EtOAc (50 mL), and combined organic layers were washed with aq 10% HCl, dried with MgSO4 and concentrated in vacuo. The crude product was purified by column chromatography on silica gel. The fraction eluted with hexane-EtOAc (100:1-20:1) afforded 2. 2a: colorless needles; mp 51 °C. 1H NMR (CDCl3): δ = 2.09 (s, 3 H), 2.37-2.41 (m, 2 H), 2.70 (s, 2 H), 2.93-2.97 (m, 2 H), 7.19-7.32 (m, 5 H). 13C NMR (CDCl3): δ = 21.3, 30.4, 43.8, 66.3, 74.4, 80.0, 126.2, 128.5, 128.5, 140.6, 168.3. FAB-MS: m/z = 249 [M+ + Na]. IR (KBr): 3253, 2935, 2120, 1748 cm-1. Anal. Calcd for C15H14O2: C, 79.62; H, 6.24. Found: C, 79.41; H, 6.41. 2b: colorless oil. 1H NMR (CDCl3): δ = 2.07 (s, 3 H), 2.66 (s, 2 H), 3.37 (s, 2 H), 7.25-7.39 (m, 5 H). 13C NMR (CDCl3): δ = 21.4, 47.6, 66.7, 74.9, 79.8, 127.5, 127.9, 131.2, 133.7, 168.2. HRMS-EI: m/z [M+] calcd for C14H12O2: 212.0837; found: 212.0833. IR (KBr): 3270, 2122, 1744 cm-1. 2c: colorless oil. 1H NMR (CDCl3): δ = 0.89 (t, J = 6.8 Hz, 3 H), 1.26-1.38 (m, 10 H), 1.58-1.66 (m, 2 H), 2.04-2.08 (m, 2 H), 2.09 (s, 3 H), 2.64 (s, 2 H). 13C NMR (CDCl3): δ = 14.1, 21.4, 22.7, 23.9, 29.1, 29.2, 29.4, 31.8, 42.2, 66.8, 73.5, 80.3, 168.3. FAB-MS: m/z = 235 [M+ + H]. IR (KBr): 3291, 2929, 2123, 1757 cm-1. Anal. Calcd for C15H22O2: C, 77.88; H, 9.46. Found: C, 76.12; H, 9.53. 2d: colorless oil. 1H NMR (CDCl3): δ = 0.92 (t, J = 7.0 Hz, 3 H), 1.33-1.38 (m, 4 H), 1.59-1.67 (m, 2 H), 2.03-2.08 (m, 2 H), 2.09 (s, 3 H), 2.64 (s, 2 H). 13C NMR (CDCl3): δ = 13.9, 21.4, 22.4, 23.6, 31.3, 42.2, 66.8, 73.6, 80.3, 168.4. HRMS-EI: m/z [M+] calcd for C12H16O2: 192.1150; found: 192.1143. IR (KBr): 3292, 2958, 2123, 1756 cm-1. 2e: colorless needles; mp 47 °C. 1H NMR (CDCl3): δ = 2.09 (s, 3 H), 2.69 (s, 2 H), 4.36 (s, 2 H), 6.97-7.01 (m, 3 H), 7.24-7.31 (m, 2 H). 13C NMR (CDCl3): δ = 21.2, 65.7, 73.4, 74.9, 77.7, 115.4, 121.9, 129.5, 158.4, 168.1. HRMS-EI: m/z [M+] calcd for C14H12O3: 228.0787; found: 228.0786. IR (KBr): 3281, 2132, 1767 cm-1.

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Reaction of 2; General Procedure: A 20-mL round-bottomed flask, containing a magnetic stirring bar, catalyst (0.015 mmol), 2 (0.3 mmol) and MeOH (5 mL) was fitted with a Dimroth condenser capped with a rubber septum. After being stirred for a certain period at 60 °C, the mixture was diluted with EtOAc (20 mL) and washed with aq 3% NaHCO3 (20 mL). The organic layers were separated, the aqueous layer was extracted with EtOAc (30 mL), and combined organic layers were dried with MgSO4 and concentrated in vacuo. The crude product was purified by column chromatography on silica gel. The fraction eluted with hexane-EtOAc (100:1-50:1 and 10:1) afforded 3 and 4, respectively. 3a: colorless oil. 1H NMR (CDCl3): δ = 1.69-1.78 (m, 1 H), 1.91-2.00 (m, 1 H), 2.22 (s, 3 H), 2.43 (dd, J = 4.4, 16.8 Hz, 1 H), 2.58-2.62 (m, 2 H), 2.80 (dd, J = 9.6, 16.8 Hz, 1 H), 2.99-3.07 (m, 1 H), 3.66 (s, 3 H), 7.15-7.32 (m, 5 H). 13C NMR (CDCl3): δ = 29.5, 32.8, 33.1, 34.9, 47.4, 51.7, 126.2, 128.2, 128.5, 140.9, 172.7, 210.5. HRMS-EI: m/z [M+] calcd for C14H18O3: 234.1256; found: 234.1252. IR (KBr): 1736, 1712 cm-1. 3b: colorless oil. 1H NMR (CDCl3): δ = 2.06 (s, 3 H), 2.28 (dd, J = 4.4, 17.0 Hz, 1 H), 2.54 (dd, J = 8.4, 13.6 Hz, 1 H), 2.70 (dd, J = 10.0, 17.0 Hz, 1 H), 2.87 (dd, J = 7.2, 13.6 Hz, 1 H), 3.18-3.25 (m, 1 H), 3.55 (s, 3 H), 7.07-7.24 (m, 5 H). 13C NMR (CDCl3): δ = 30.3, 35.0, 37.6, 49.6, 51.6, 126.7, 128.6, 128.8, 138.1, 172.6, 210.6. HRMS-EI: m/z [M+] calcd for C13H16O3: 220.1100; found: 220.1097. IR (KBr): 1738, 1205 cm-1. 3c: colorless oil. 1H NMR (CDCl3): δ = 0.81 (t, J = 6.8 Hz, 3 H), 1.14-1.38 (m, 13 H), 1.49-1.56 (m, 1 H), 2.16 (s, 3 H), 2.28 (dd, J = 4.4, 16.8 Hz, 1 H), 2.67 (dd, J = 10.0, 16.8 Hz, 1 H), 2.88-2.95 (m, 1 H), 3.58 (s, 3 H). 13C NMR (CDCl3): δ = 14.0, 22.6, 26.8, 29.1, 29.3, 29.5, 29.5, 31.3, 31.8, 34.9, 47.9, 51.6, 173.0, 210.9. HRMS-EI: m/z [M+] calcd for C14H26O3: 242.1882; found: 242.1893. IR (KBr): 2928, 1739, 1715 cm-1. 3d: colorless oil. 1H NMR (CDCl3): δ = 0.81 (t, J = 6.8 Hz, 3 H), 1.17-1.21 (m, 6 H), 1.25-1.38 (m, 1 H), 1.50-1.59 (m, 1 H), 2.16 (s, 3 H), 2.28 (dd, J = 4.4, 16.8 Hz, 1 H), 2.67 (dd, J = 10.0, 16.8 Hz, 1 H), 2.88-2.95 (m, 1 H), 3.58 (s, 3 H). 13C NMR (CDCl3): δ = 13.9, 22.3, 26.5, 29.5, 31.2, 31.7, 34.9, 47.9, 51.6, 172.9, 210.9. HRMS-EI: m/z [M+] calcd for C11H20O3: 200.1413; found: 200.1416. IR (KBr): 2932, 1739, 1714 cm-1. 3f: colorless oil. 1H NMR (CDCl3): δ = 0.92 (d, J = 6.8 Hz, 6 H), 1.69-1.78 (m, 1 H,), 1.86-2.01 (m, 2 H), 2.22 (s, 3 H), 2.44 (dd, J = 4.8, 16.8 Hz, 1 H), 2.55-2.66 (m, 2 H), 2.81 (dd, J = 9.6, 16.8 Hz, 1 H), 2.99-3.06 (m, 1 H), 3.80-3.88 (m, 2 H), 7.15-7.31 (m, 5 H). 13C NMR (CDCl3): δ = 19.0, 27.6, 29.5, 32.9, 33.1, 35.2, 47.5, 70.8, 126.2, 128.2, 128.5, 141.0, 172.3, 210.5. HRMS-EI: m/z [M+] calcd for C17H24O3: 276.1726; found: 276.1721. IR (KBr): 2962, 1733, 1160 cm-1. 4a: colorless oil. 1H NMR (CDCl3): δ = 1.41 (d, J = 6.8 Hz, 3 H), 2.54-2.76 (m, 2 H), 2.92 (t, J = 8.0 Hz, 2 H), 4.90 (dq, J = 1.6, 6.8 Hz, 1 H), 5.81 (q, J = 1.6 Hz, 1 H), 7.18-7.34 (m, 5 H). 13C NMR (CDCl3): δ = 18.2, 29.5, 33.1, 80.4, 115.6, 126.7, 128.1, 128.7, 139.7, 172.9, 173.1. HRMS-EI: m/z [M+] calcd for C13H14O2: 202.0994; found: 202.0996. IR (KBr): 2928, 1755, 1639 cm-1. 4b: colorless oil. 1H NMR (CDCl3): δ = 1.38 (d, J = 6.8 Hz, 3 H), 3.48 (dd, J = 1.6, 16.8 Hz, 1 H), 3.68 (d, J = 16.8 Hz, 1 H), 4.86 (br q, J = 6.8 Hz, 1 H), 5.59 (d, J = 1.6 Hz, 1 H), 7.10-7.30 (m, 5 H). 13C NMR (CDCl3): δ = 18.3, 34.6, 79.9, 116.7, 127.3, 128.8, 129.0, 135.5, 172.6, 172.9. HRMS-EI: m/z [M+] calcd for C12H12O2: 188.0837; found: 188.0834. IR (KBr): 2932, 1737, 1639 cm-1. 4c: colorless oil. 1H NMR (CDCl3): δ = 0.84 (t, J = 6.4 Hz, 3 H), 1.17-1.34 (m, 10 H), 1.38 (d, J = 6.8 Hz, 3 H), 1.48-1.58 (m, 2 H), 2.16-2.37 (m, 2 H), 4.89 (dq, J = 1.6, 6.8 Hz, 1 H), 5.72 (d, J = 1.6 Hz, 1 H). 13C NMR (CDCl3): δ = 14.0, 18.2, 22.5, 26.9, 27.9, 29.0, 29.1, 29.1, 31.7, 80.3, 114.8, 173.1, 174.5. HRMS-EI: m/z [M+] calcd for C13H22O2: 210.1620; found: 210.1629. IR (KBr): 2927, 1755, 1639 cm-1. 4d: colorless oil. 1H NMR (CDCl3): δ = 0.84 (t, J = 7.2 Hz, 3 H), 1.26-1.31 (m, 4 H), 1.36 (d, J = 6.8 Hz, 3 H), 1.49-1.57 (m, 2 H), 2.14-2.35 (m, 2 H), 4.87 (dq, J = 1.2, 6.8 Hz, 1 H), 5.70 (d, J = 1.6 Hz, 1 H). 13C NMR (CDCl3): δ = 13.8, 18.2, 22.2, 26.5, 27.8, 31.3, 80.3, 114.8, 173.1, 174.5. HRMS-EI: m/z [M+] calcd for C10H16O2: 168.1150; found: 168.1144. IR (KBr): 2932, 1754, 1638 cm-1. 5: colorless oil; diastereomeric mixture, ratio = 2.3:1. 1H NMR (CDCl3, major diastereomer): δ = 1.66 (s, 3 H), 2.05-2.25 (m, 2 H), 2.66 (s, 1 H), 2.79-2.96 (m, 2 H), 3.40 (s, 3 H), 4.18 (d, J = 2.8 Hz, 1 H), 4.50 (d, J = 2.8 Hz, 1 H), 7.18-7.32 (m, 5 H). 13C NMR (CDCl3, major diastereomer): δ = 24.0, 30.3, 44.4, 50.1, 73.9, 78.8, 80.8, 82.4, 123.1, 126.1, 128.4, 128.5, 141.0, 159.8. HRMS-EI: m/z [M+] calcd for C16H18O3: 258.1256; found: 258.1258. IR (KBr): 3287, 2117, 1687, 1052 cm-1.