Synthesis of homoallylic alcohols from ketones in water

Article abstract of DOI:10.1080/00397910500377560

Homoallylic alcohols have been prepared in good yields by allylation of ketones with allyl bromide in the presence of stannous chloride dihydrate, zinc iodide, and ammonium chloride in water. Copyright Taylor & Francis LLC.

Full text of DOI:10.1080/00397910500377560

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Synthesis of Homoallylic Alcohols From
Ketones in Water
Jun Wang a & Gu Yuan a
a Key Laboratory of Bioorganic Chemistry and Molecular Engineering
of Ministry of Education, Department of Chemical Biology, College of
Chemistry , Peking University , Beijing, China
Published online: 19 Aug 2006.
To cite this article: Jun Wang & Gu Yuan (2006) Synthesis of Homoallylic Alcohols From Ketones in Water,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
36:3, 401-405, DOI: 10.1080/00397910500377560
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Synthetic Communicationsw, 36: 401–405, 2006
Copyright # Taylor & Francis LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500377560
Synthesis of Homoallylic Alcohols
From Ketones in Water
Jun Wang and Gu Yuan
Key Laboratory of Bioorganic Chemistry and Molecular Engineering
of Ministry of Education, Department of Chemical Biology,
College of Chemistry, Peking University, Beijing, China
Abstract: Homoallylic alcohols have been prepared in good yields by allylation of
ketones with allyl bromide in the presence of stannous chloride dihydrate, zinc
iodide, and ammonium chloride in water.
Keywords: Allylation, aqueous media, stannous chloride, zinc iodide
Homoallylic alcohols are very useful intermediates and are widely used in
organic synthesis.[1] Numerous methods for the synthesis of homoallylic
alcohols have been developed.[2] Recently, the synthesis of homoallylic
alcohols in aqueous media has drawn much interest because the reactions
offer the operational simplicity and the advantages of using an environmen-
tally friendly solvent. Many metals have been used to mediate the carbonyl
allylation in aqueous media, such as indium,[3] zinc,[4] and tin.[5] Some of
the reactions give good yields; however, the use of these zero-valent metals
unavoidably leads to problems because the metal-mediated allylation is a het-
erogeneous reaction in water. For instance, it is often difficult to stir the
reaction mixture and metal oxide or hydroxide precipitation on the surface
of metal may slow or stop the reaction.
Received in Japan July 21, 2005
Address correspondence to Gu Yuan, Key Laboratory of Bioorganic Chemistry and
Molecular Engineering of Ministry of Education, Department of Chemical Biology,
College of Chemistry, Peking University, Beijing 100871, China. Fax: þ86-10-
62751708; E-mail: guyuan@pku.edu.cn
401

402
J. Wang and G. Yuan
Water-soluble reductive metal salts, such as SnCl2, can provide an
alternative way to mediate the coupling between allyl halide and carbonyl
compounds to produce the corresponding homoallylic alcohols in aqueous
media, which can solve these problems when the salt is applied in the
reaction. Nevertheless, SnCl2 cannot efficiently mediate the coupling
between allyl bromide and a carbonyl compound in water stirred at room
temperature. Therefore, some water-soluble catalyst was introduced into the
system to catalyze the reactions, for example TiCl3,[6] Cu(II),[7] or Pd
(II).[8] In addition, the formation of homoallylic alcohols mediated by SnCl2
can also be activated by addition of potassium iodide in water.[9] But most
of the carbonyl compounds used in these reactions to produce homoallylic
alcohols are aldehydes. The allylation of ketones under the same condition
does not successfully proceed because of the inactivity of ketones compared
to aldehydes, so there are few publications describing the direct synthesis of
homoallylic alcohols from ketones in water, except those where ultrasonica-
tion[10] or water-insoluble Cu powder catalyst[11] was applied. Consequently,
it is essential that a new method should be developed to efficiently allylate
ketones with water-soluble salts and catalysts without using other special
appliances under mild conditions.
In this article, we report a mild and simple synthesis of homoallylic
alcohols from ketones by treatment with allyl bromide, SnCl2, ZnI2 and
NH4Cl in water (Scheme 1). The system of zinc iodide and ammonium
chloride has a good solubility in water and can smoothly catalyze the reaction.
The experimental results are summarized in Table 1.
As shown in Table 1, both aliphatic and aromatic ketones can smoothly
be allylated and offer good yields in the reaction. Aromatic ketone (entry 6)
and a,b-unsaturated ketone (entry 8) need longer time to react with allyl
bromide than aliphatic ketones under the condition. Owing to the different
strain of the rings, cyclohexanone (entry 5) provides a higher yield than
cyclopentanone (entry 4). It was noticed that an ester-containing substrate
(entry 7) was successfully allylated without affecting the ester group. Also,
a,b-unsaturated ketone (entry 8) was efficiently allylated, whereas carbon–
carbon double bond was not changed.
In summary, we report here a simple and efficient method to synthesize
homoallylic alcohols in good yields from ketones in water. The reaction
extends the scope of substrates that were used to synthesize homoallylic
alcohols in water. Ketones that often are inert to allylation mediated by
Scheme 1.

Homoallylic Alcohols from Ketones
Table 1. Allylation of various ketones in water
Time
403
Yield
(%)a
Entry
Substrates
Products
(h)
1
15
65
73
68
2
3
4
5
15
17
20
16
60
81
6
22
62
7
8
17
20
72
66
aIsolated yield.
SnCl2 in aqueous media were successfully allylated in the reaction. More
kinds of homoallylic alcohols can be prepared by the method.
EXPERIMENTAL
Typical Procedures for the Allylation of Ketones
ZnI2 (0.8 mmol) and NH4Cl (0.8 mmol) were added to a mixture of ketone
(1 mmol) and allyl bromide (1.4 mmol) in water (3 mL). After the mixture

404
J. Wang and G. Yuan
.
was stirred about 1 min, SnCl2 2H2O (1.5 mmol) was added. The mixture was
vigorously stirred at room temperature (308C) for several hours. Then, the
mixture was extracted with diethyl ether directly (3 ꢀ 10 mL). The
combined ether was washed with brine (2 ꢀ 10 mL). After the operation,
the organic layer was dried over anhydrous sodium sulfate, filtered, and
then evaporated. The residue was purified by flash chromatography (silica
1
gel; ether–petroleum ether). The structure of products was identified by H
NMR, 13C NMR, and IR spectra.
Representative Spectroscopic Data
1
Compound 2b: IR (KBr): n 3390, 3077, 1640, 1149; H NMR (300 MHz,
CDCl3): d 5.82–5.91 (m, 1H), 5.09–5.16 (m, 2H), 2.22 (d, J ¼ 7.9 Hz, 2H),
1.65 (br, 1H), 1.51 (q, J ¼ 7.5 Hz, 2H), 1.16 (s, 3H), 0.92 (t, J ¼ 7.4 Hz,
3H); 13C NMR (75 MHz, CDCl3): d 134.1, 118.4, 72.3, 45.7, 34.2, 26.1, 8.1.
Compound 5b: IR (KBr): n 3408, 3075, 2932, 2857, 1639, 1448, 1265, 1140;
1H NMR (300 MHz, CDCl3): d 5.85–5.94 (m, 1H), 5.07–5.17 (m, 2H), 2.22
(d, J ¼ 7.2 Hz, 2H), 1.42–1.63 (m, 10H), 1.29 (br, 1H); 13C NMR (75 MHz,
CDCl3): d 133.7, 118.6, 70.9, 46.7, 37.4, 25.7, 22.1.
1
Compound 6b: IR (KBr): n 3445, 3062, 2978, 1640, 1494, 1446, 1069; H
NMR (300 MHz, CDCl3): d 7.42–7.46 (m, 2H), 7.32–7.37 (m, 2H), 7.21–
7.27 (m, 1H), 5.54–5.68 (m, 1H), 5.09–5.17 (m, 1H), 2.65–2.73 (m, 1H),
2.46–2.54 (m, 1H), 2.07 (br, 1H), 1.55 (s, 3H); 13C NMR (75 MHz,
CDCl3): d 147.6, 133.6, 128.1, 126.6, 124.7, 119.5, 73.6, 48.4, 29.9.
1
Compound 7b: IR (KBr): n 3513, 3078, 2981, 1717, 1641, 1371, 1195; H
NMR (300 MHz, CDCl3): d 5.80–5.90 (m, 1H), 5.05–5.14 (m, 2H), 4.18
(q, J ¼ 7.2 Hz, 2H), 3.45 (s, 1H), 2.39–2.55 (q, J ¼ 15.6 Hz, 2H), 2.29
(d, J ¼ 7.5 Hz, 2H), 1.25–1.32 (m, 6H); 13C NMR (75 MHz, CDCl3):
d 172.9, 133.6, 118.4, 70.6, 60.5, 46.4, 44.3, 26.7, 14.1.
REFERENCES
1. (a) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207; (b) Marshall, J. A. Chem.
Rev. 1996, 96, 31; (c) Chen, G. M.; Brown, H. C.; Ramachandran, P. V. J. Org.
Chem. 1999, 64, 721; (d) Zhang, W. C.; Li, C. J. Tetrahedron 2000, 56, 2403;
(e) Jaber, J. J.; Mitsui, K.; Rychnovsky, S. D. J. Org. Chem. 2001, 66, 4679;
(f) Balskus, E. P.; Mendez-Andino, J.; Arbit, R. M.; Paquette, L. A. J. Org.
Chem. 2001, 66, 6695.
2. (a) Wang, W.; Shi, L.; Huang, Y. Tetrahedron 1990, 46, 3315; (b) Ren, P. D.;
Pan, S. F.; Dong, T. W.; Wu, S. H. Chin. J. Chem. 1996, 14, 462;
(c) Ren, P. D.; Jin, Q. H.; Yao, Z. P. Synth. Commun. 1997, 27, 2761;

Homoallylic Alcohols from Ketones
405
(d) Zhou, J. Y.; Jia, Y.; Sun, G. F.; Wu, S. H. Synth. Commun. 1997, 27, 1899;
(e) Li, C. J.; Meng, Y.; Yi, X. H.; Ma, J. H.; Chan, T. H. J. Org. Chem. 1998,
63, 7498; (f) Miyamoto, H.; Daikawa, N.; Tanaka, K. Tetrahedron Lett. 2003,
44, 6963.
3. (a) Li, C. J.; Chan, T. H. Tetrahedron 1994, 55, 11149; (b) Cintas, P. Synlett. 1995,
1087; (c) Chan, Y. H.; Yang, Y. J. Am Chem. Soc. 1999, 121, 3228; (d) Loh, T. P.;
Zhou, J. R.; Yin, Z. Org. Lett. 1999, 1, 1855; (e) Hilt, G.; Smolko, K. I.; Waloch, C.
Tetrahedron Lett. 2002, 43, 1437; (f) Podlech, J.; Maier, T. C. Synthesis 2003, 633.
4. (a) Petrier, C.; Luche, J. L. J. Org. Chem. 1985, 50, 910; (b) Deng, D. L.; Lu, Z. H.
Chin. Chem. Lett. 1994, 5, 173; (c) Deng, D. L.; Lu, Z. H.; Wu, K. Chin. J. Org.
Chem. 1996, 16, 462; (d) Marton, D.; Stivanello, D.; Tagliavini, G. J. Org. Chem.
1996, 61, 2731; (e) Yi, X. H.; Haberman, J. X.; Li, C. J. Synth. Commun. 1998, 28,
2999; (f) Zhou, C. L.; Zhou, Y. Q.; Jiang, J. Y.; Xie, Z.; Wang, Z. Y.; Zhang, J. H.;
Wu, J. H.; Yin, H. Tetrahedron Lett. 2004, 45, 5537.
5. (a) Mukaiyama, T.; Harada, T. Chem. Lett. 1981, 1527; (b) Wu, S. H.;
Huang, B. Z.; Gao, X. Synth. Commun. 1990, 20, 1279; (c) Wu, S. H.;
Huang, B. Z.; Zhu, T. M.; Yiao, D. Z.; Chu, Y. L. Acta Chim. Sin. 1990, 48,
372; (d) Chan, T. H.; Yang, Y.; Li, C. J. J. Org. Chem. 1999, 64, 4452.
6. Tan, X. H.; Shen, B.; Deng, W.; Zhao, H.; Liu, L.; Guo, Q. X. Org. Lett. 2003, 5,
1833.
7. Kundu, A.; Prabhakar, S.; Vairamani, M.; Roy, S. Organometallics 1997, 16, 4796.
8. (a) Okano, T.; Kiji, J.; Doi, T. Chem. Lett. 1998, 5; (b) Tan, X. H.; Hou, Y. Q.;
Shen, B.; Liu, L.; Guo, Q. X. Tetrahedron Lett. 2004, 45, 5525.
9. (a) Houllemare, D.; Outurquin, F.; Paulmier, C. J. Chem. Soc., Perkin Trans. 1
1997, 1629; (b) Gremyachinskiy, D. E.; Smith, L. L.; Gross, P. H.;
Samoshin, V. V. Green Chemistry 2002, 4, 317; (c) Samoshin, V. V.;
Gremyachinskiy, D. E.; Smith, L. L.; Bliznets, I. V.; Gross, P. H. Tetrahedron
Lett. 2002, 43, 6329.
10. Wang, J.; Yuan, G.; Dong, C. Q. Chem. Lett. 2004, 33, 286.
11. Tan, X. H.; Shen, B.; Liu, L.; Guo, Q. X. Tetrahedron Lett. 2002, 43, 9373.