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References and notes
[Fe]
FeCl3
H
O
1. Alonso, F.; Beletskaya, I. P.; Yus, M. Chem. Rev. 2004, 104, 3079–3159.
2. Ma, S. Pure Appl. Chem. 2006, 78, 197–208.
..
+
3. Hashmi, A. S. K. Angew. Chem., Int. Ed. 2000, 39, 3590–3593.
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O
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2006, 12, 6356–6365.
Scheme 2.
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8. Qian, H.; Han, X.; Widenhoefer, R. A. J. Am. Chem. Soc. 2004, 126, 9536–9537.
9. Hensen, K.; Mahaim, C.; Hölderich, W. F. Stud. Surf. Sci. Catal. 1997, 105B, 1133–
1140.
10. Hensen, K.; Mahaim, C.; Hölderich, W. F. Appl. Catal., A 1997, 149, 311–329.
11. Oe, Y.; Ohta, T.; Ito, Y. Synlett 2005, 179–181.
12. Gligorich, K. M.; Schultz, M. J.; Sigman, M. S. J. Am. Chem. Soc. 2006, 128, 2794–
2795.
13. Matsukawa, Y.; Mizukado, J.; Quan, H.; Tamura, M.; Sekiya, A. Angew. Chem.,
Int. Ed. 2005, 44, 1128–1130.
14. (a) Bolm, C.; Legros, J.; Le Paih, J.; Zani, L. Chem. Rev. 2004, 104, 6217–6254; (b)
Rueping, M.; Nachtsheim, B. J.; Scheidt, T. Org. Lett. 2006, 8, 3717–3719; (c)
Komeyama, K.; Morimoto, T.; Takaki, K. Angew. Chem. Int. Ed. 2006, 45, 2938–
2941; (d) Kischel, J.; Jovel, I.; Mertins, K.; Zapf, A.; Beller, M. Org. Lett. 2006, 8,
19–22; (e) Díaz, D. D.; Miranda, P. O.; Padrón, J. I.; Martín, V. S. Curr. Org. Chem.
2006, 10, 457–476; (f) Iovel, I.; Mertins, K.; Kischel, J.; Zapf, A.; Beller, M.
Angew. Chem., Int. Ed. 2005, 44, 3913–3917; (g) Komeyama, K.; Morimoto, T.;
Nakayama, Y.; Takaki, K. Tetrahedron Lett. 2007, 48, 3259–3261; (h) Rosenfeld,
D. C.; Shekhar, S.; Takemiya, A.; Utsunomiya, M.; Hartwig, J. F. Org. Lett. 2006, 8,
4179–4182.
of nucleophile follows Markovnikov’s rule. Finally monoterpenes
were converted into terpinol derivatives.
In the absence of catalyst, the reaction failed to give the desired
product. The products were characterized by 1H NMR, IR and mass
spectrometry and also by comparison with authentic samples.15
The advantages of this procedure include mild conditions as well
as short reaction times, easy work-up and good yields. There was
no considerable difference in yields when comparing
a-pinene,
b-pinene, limonene and isolimonene. In the case of isolimonene,
no racemization was observed. No chlorination of monoterpenes
was observed under the reaction conditions. However, aromatic
alcohols failed to give the desired product under the reaction
conditions. Among various Lewis acids such as TiCl4, SnCl4 and
BF3.OEt2 tested, FeCl3 was found to be superior in terms of conver-
15. Lemechko, P.; Grau, F.; Antoniotti, S.; Duñach, E. Tetrahedron Lett. 2007, 48,
5731–5734.
sion. For example, a-pinene and benzyl alcohol in the presence of
TiCl4, SnCl4, BF3.OEt2 and FeCl3 gave the product 3a in 45%, 52%,
65% and 80% yields, respectively. Furthermore, we have examined
the possibility of FeCl3 functioning catalytically or at least less than
20 mol %. Though reactions proceeded with 10 mol % FeCl3, long
reaction times (8–12 h) were required to achieve comparable
yields. But best results were obtained with 20 mol % of FeCl3. The
scope and generality of this process are illustrated with respect
to various alcohols and monoterpenes and the results are pre-
sented in Table 1.16
In summary, anhydrous FeCl3 has proved to be a useful and
highly efficient catalyst for the hydroalkoxylation of unactivated
alkenes under mild conditions. In addition to its simplicity and effi-
ciency, this method produces alkoxy monoterpenes in excellent
yields in short reaction times. This method provides an easy access
to a wide range of alkoxy monoterpenes. The use of readily avail-
able FeCl3 makes this method simple, convenient, cost-effective
and practical.
16. General procedure: To a stirred solution of
a-pinene (163 mg, 1.2 mmol) and
benzyl alcohol (108 mg, 1.0 mmol) in dichloromethane (4 mL) was added FeCl3
(32 mg, 0.2 mmol) at 0 °C. The resulting mixture was stirred at room
temperature for the appropriate time (Table 1). After complete conversion as
indicated by TLC, the reaction mixture was quenched with water (5 mL) and
extracted with dichloromethane (3 Â 10 mL). The combined organic layers
were dried over anhydrous Na2SO4 and concentrated in vacuo. The resulting
product was purified by column chromatography to afford pure alkoxy
monoterpene derivative. Spectroscopic data for selected products: 4-(1-
(benzyloxy)-1-methylethyl)-1-methyl-cyclohexene (3a): Liquid, IR (KBr):
m
3027, 2966, 2923, 1721, 1604, 1450, 1378, 1249, 1144, 1059, 912, 734,
696 cmÀ1 1H NMR (300 MHz, CDCl3): d 1.20 (s, 6H), 1.23–1.40 (m, 1H), 1.63 (s,
;
3H), 1.67–2.10 (m, 6H), 4.40 (s, 2H), 5.35 (br s, 1H), 7.14–7.32 (m, 5H). 13C NMR
(CDCl3, 75 MHz): d 22.1, 22.5, 22.9, 23.5, 26.4, 30.6, 41.8, 62.6, 120.4, 126.4,
126.6, 127.7, 129.2, 132.5, 133.4; ESI-MS: m/z: 245 (M+H+), 227, 201, 189, 178,
161, 149, 138. 4-(1-isopropoxy-1-methylethyl)-1-methyl-cyclohexene (3h):
Liquid, IR (KBr):
m
2966, 2924, 1723, 1637, 1495, 1451, 1381, 1220, 1060,
1025, 913, 733, 695 cmÀ1
;
1H NMR (300 MHz, CDCl3): d 1.04–1.08 (d, J = 2.2 Hz,
6H,), 1.09 (s, 6H), 1.12–1.30 (m, 1H), 1.45–1.58 (m, 1H), 1.62 (s, 3H), 1.66–2.05
(m, 5H), 3.70–3.84 (m, 1H), 5.32 (br s, 1H). 13C NMR (CDCl3, 75 MHz): d 23.2,
23.7, 24.1, 24.4, 25.4, 25.6, 27.6, 31.5, 43.4, 63.1, 121.3, 134.4; LC–MS: m/z: 197
(M+H+), 179, 102, 74, 59. 4-(1-methoxy-1-methylethyl)-1-methyl-1-cyclohexene
(3k): Liquid, IR (KBr):
m ;
2923, 2853, 1645, 1539, 1458, 1376, 1079, 760 cmÀ1
1H NMR (200 MHz, CDCl3): d 1.09 (s, 6H), 1.14–1.33 (m, 1H), 1.59–2.06 (m, 9H),
3.16 (s, 3H), 5.34 (br s, 1H). 13C NMR (CDCl3, 75 MHz): d 21.8, 22.3, 23.3, 23.8,
26.8, 29.6, 31.0, 41.4, 48.6, 120.8, 133.9; LC–MS: m/z:169 (M+H+), 140, 111.
Acknowledgement
G.N. and K.V.P. thank CSIR New Delhi for the award of
fellowships.