LETTER
Construction of 1H-Inden-1-one
261
7.76 (d, J = 15.6 Hz, 1 H), 7.47–7.61 (m, 3 H), 7.39 (d,
In summary, a novel approach to construct 1H-inden-1-
one was described. The indenone/indanone skeleton is a
fairly common benzannulated motif in many natural
products.9 Because of their exciting pharmacological
properties, e.g., cytotoxic,10,11 anti-HIV,11 and antibacteri-
al activies,12 much attention has been paid to the synthesis
of these molecules and several synthetic methods have
been developed to construct their skeleton.13 Further
applications of this methodology in natural product syn-
thesis are being pursued in our laboratory.
J = 15.6 Hz, 1 H), 6.92 (d, J = 7.2 Hz, 2 H). 13C NMR (75
MHz, CDCl3): d = 190.6, 161.6, 144.7, 138.4, 132.5, 130.2,
128.5, 128.3, 127.5, 119.7, 114.3, 55.3. ESI-HRMS: m/z
calcd for C16H13O [M + H]+: 221.0966; found: 221.0963.
2-(4-Methoxyphenyl)-3-phenyl-1H-inden-1-one (4c).
1H NMR (300 MHz, CDCl3): d = 7.55 (d, J = 6.3 Hz, 1 H),
7.41–7.43 (m, 5 H), 7.28–7.41 (m, 3 H), 7.20 (d, J = 6.3 Hz,
2 H), 7.09 (d, J = 7.2 Hz, 1 H), 6.78 (d, J = 6.3 Hz, 2 H). 13
NMR (75 MHz, CDCl3): d = 197.0, 159.1, 153.7, 145.5,
133.4, 132.9, 131.8, 131.2, 130.6, 129.1, 128.7, 128.6,
128.4, 123.0, 122.8, 120.9, 113.6, 55.1. ESI-HRMS: m/z
C
calcd for C22H17O2 [M + H]+: 313.1223; found: 313.1225.
3-(4-Methoxyphenyl)-2-phenyl-1H-inden-1-one (4d).
1H NMR (300 MHz, CDCl3): d = 7.56 (d, J = 7.2 Hz, 1 H),
7.19–7.38 (m, 11 H), 6.91 (d, J = 8.7 Hz, 2 H), 3.85 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 196.4, 160.4, 155.2, 145.1,
133.2, 131.6, 131.0, 130.2, 129.9, 128.8, 128.1, 127.5,
126.1, 124.7, 122.7, 121.2, 114.1, 55.2. ESI-HRMS: m/z
calcd for C22H17O2 [M + H]+: 313.1223; found: 313.1223.
3-(4-Nitrophenyl)-2-phenyl-1H-inden-1-one (4e).
1H NMR (300 MHz, CDCl3): d = 8.26 (d, J = 8.1 Hz, 2 H),
7.60 (d, J = 7.2 Hz, 1 H), 7.55 (d, J = 8.1 Hz, 2 H), 7.19–7.44
(m, 7 H), 7.07 (d, J = 6.9 Hz, 1 H). 13C NMR (75 MHz,
CDCl3): d = 195.5, 152.2, 147.9, 144.2, 139.5, 134.0, 133.8,
130.1, 129.8, 129.5, 129.4, 128.3, 124.1, 123.5, 120.8. FAB-
MS: m/z = 328.1, 307.2.
Acknowledgment
The authors are grateful for the generous financial support by the
Special Doctorial Program Funds of the Ministry of Education of
China (20040730008), A Hundred Talents Program of CAS, NSFC
(QT program, No.20372026) and the Key Grant Project of Chinese
Ministry of Education (No.105169).
References and Notes
(1) (a) Heck, R. F. Org. React. 1982, 27, 345. (b) de Meijere,
A.; Meyer, F. E. Angew. Chem., Int. Ed. Engl. 1994, 33,
2379. (c) Cabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28,
2. (d) Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000,
100, 3009. (e) Amatore, C.; Jutand, A. Acc. Chem. Res.
2000, 33, 314. (f) McClure, K. F.; Danishefsky, S. J. J. Am.
Chem. Soc. 1993, 115, 6094.
4,6-Dimethoxy-3-phenyl-1H-inden-1-one (4f).
1H NMR (300 MHz, CDCl3): d = 7.60 (d, J = 6.9 Hz, 2 H),
7.42–7.48 (m, 3 H), 6.81 (d, J = 1.8 Hz, 1 H), 6.44 (d, J = 1.8
Hz, 1 H), 5.69 (s, 1 H), 3.85 (s, 3 H), 3.68 (s, 3 H). 13C NMR
(75 MHz, CDCl3): d = 196.5, 166.3, 163.1, 136.1, 134.9,
130.9, 129.7, 127.8, 127.6, 122.1, 107.2, 103.2, 102.6, 55.8,
54.3. ESI-HRMS: m/z calcd for C17H14O3Na [M + Na]+:
289.0835; found: 289.0832.
(2) Link, J. Org. React. 2002, 60, 157.
(3) (a) Shibasaki, M.; Vogl, E. M. Adv. Synth. Catal. 2004, 346,
1533. (b) Dounay, A. B.; Overman, L. E. Chem. Rev. 2003,
103, 2945.
(4) Gaudin, J. M. Tetrahedron Lett. 1991, 32, 6113.
(5) Bei, X.; Hagemeyer, A.; Volpe, A.; Saxton, R.; Turner, H.;
Guram, A. S. J. Org. Chem. 2004, 69, 8626.
2-(4-Methoxyphenyl)-3-(4-nitrophenyl)-1H-inden-1-one
(4g).
1H NMR (300 MHz, CDCl3): d = 8.27 (d, J = 8.7 Hz, 2 H),
7.56–7.60 (m, 3 H), 7.36–7.41 (m, 1 H), 7.25–7.32 (m, 1 H),
7.15 (d, J = 9.0 Hz, 2 H), 7.02 (d, J = 6.9 Hz, 1 H), 6.79 (d,
J = 9.0 Hz, 2 H), 3.79 (s, 3 H). 13C NMR (75 MHz, CDCl3):
d = 196.0, 159.7, 150.6, 147.8, 144.6, 140.0, 133.7, 133.5,
131.2, 130.1, 129.6, 129.0, 124.1, 123.4, 121.9, 120.4,
113.9, 55.2. IR (KBr): 1710, 1602, 1512, 1456, 1343, 1292,
1250, 1177 cm–1. FAB-MS: m/z = 356.9, 341.9.
(6) General Reaction Procedure.
Compound 3 (1 mmol) was dissolved in DMF (5 mL);
K2CO3 (200 mol%), Pd(OAc)2 (5 mol%) and PPh3 (15
mol%) were added in turn. The reaction was heated to 80 °C
and stirred for 24 h. The reaction mixture was extracted with
Et2O (3 × 20 mL), washed with brine, dried with Na2SO4,
filtered and evaporated under reduced pressure. The product
4 was purified by column chromatography on silica gel using
PE–EtOAc as eluent.
2,3-Dihydro-4,6-dimethoxy-3-(4-methoxyphenyl)-2-
propylideneinden-1-one (4h).
(7) Spectroscopic Data.
1H NMR (300 MHz, CDCl3): d = 7.03 (d, J = 11.7 Hz, 2 H),
6.92 (s, 1 H), 6.73–6.83 (m, 3 H), 6.56 (s, 1 H), 4.92 (s, 1 H),
3.88 (s, 3 H), 3.79 (s, 3 H), 3.64 (s, 3 H), 1.94–2.15 (m, 2 H),
0.88 (t, J = 7.5, 7.5 Hz, 3 H). 13C NMR (75 MHz, CDCl3):
d = 193.9, 161.3, 157.8, 157.5, 141.5, 140.4, 139.5, 136.1,
134.1, 129.1, 113.3, 106.1, 96.4, 55.7, 55.5, 55.0, 44.1, 22.4,
12.3. MS (EI): m/z (%) = 338 (14) [M+], 245 (43), 166 (72),
138 (100).
4,6-Dimethoxy-3-(3,5-dimethoxyphenyl)-2-(4-methoxy-
phenyl)-1H-inden-1-one (2).
1H NMR (300 MHz, CDCl3): d = 7.10 (d, J = 8.7 Hz, 2 H),
6.85 (s, 1 H), 6.73 (d, J = 8.7 Hz, 2 H), 6.49 (d, J = 2.1 Hz,
2 H), 6.43 (s, 2 H), 3.85 (s, 3 H), 3.76 (s, 3 H), 3.69 (s, 6 H),
3.60 (s, 3 H). 13C NMR (75 MHz, CDCl3): d = 196.6, 162.4,
160.1, 158.6, 156.5, 154.6, 136.9, 134.0, 130.9, 130.5,
123.5, 114.2, 108.0, 103.9, 102.6, 100.9, 55.8, 55.6, 55.3,
55.1. ESI-HRMS: m/z calcd for C26H25O6 [M + H]+:
433.1646; found: 433.1648.
(8) (a) Iida, H.; Yuasa, Y.; Kibayashi, C. J. Org. Chem. 1980,
45, 2938. (b) Steinhoff, B. A.; Fix, S. R.; Stahl, S. S. J. Am.
Chem. Soc. 2002, 124, 766. (c) Schultz, M. J.; Park, C. C.;
Sigman, M. S. Chem. Commun. 2002, 14, 3034.
2,3-Diphenyl-1H-inden-1-one (4a).
1H NMR (300 MHz, CDCl3): d = 7.58 (d, J = 6.0 Hz, 1 H),
7.40–7.42 (m, 4 H), 7.35–7.39 (m, 2 H), 7.24–7.26 (m, 6 H),
7.14 (d, J = 6.0 Hz, 1 H). 13C NMR (75 MHz, CDCl3): d =
196.5, 155.3, 145.2, 133.4, 132.6, 130.7, 129.9, 129.6,
129.3, 128.9, 128.7, 128.5, 128.0, 127.7, 126.3, 122.9,
121.2. ESI-HRMS: m/z calcd for C21H15O [M + H]+:
283.1117; found: 283.1114.
(d) Mueller, J. A.; Sigman, M. S. J. Am. Chem. Soc. 2003,
125, 7005.
(9) (a) Ito, T.; Tanaka, T.; Iinuma, M.; Nakaya, K.; Takahashi,
Y.; Sawa, R.; Murata, J.; Darnaedi, D. J. Nat. Prod. 2004,
67, 932. (b) Ernst-Russell, M. A.; Chai, C. L. L.; Wardlaw,
J. H.; Elix, J. A. J. Nat. Prod. 2000, 63, 129. (c) Fillion, E.;
Fishlock, D. J. Am. Chem. Soc. 2005, 127, 13144.
3-(4-Methoxyphenyl)-1H-inden-1-one (4b).
1H NMR (300 MHz, CDCl3): d = 8.00 (d, J = 7.2 Hz, 2 H),
Synlett 2006, No. 2, 259–262 © Thieme Stuttgart · New York