Allylation of carbonyl compounds mediated by Aluminum/Fluoride salts in water

Article abstract of DOI:10.1002/cjoc.201090115

A novel mediator (Al/KF) has been developed and employed in the Barbier-type alkylations of various aldehydes and ketones with alkyl halide in water. The carbonyl compounds could be effectively converted into corresponding homoallylic alcohol in good yiel

Full text of DOI:10.1002/cjoc.201090115

FULL PAPER
Allylation of Carbonyl Compounds Mediated by
Aluminum/Fluoride Salts in Water
Yuan, Shizhen*(袁仕祯)
Liu, Jin(刘瑾)
Xu, Ling(徐玲)
Zhu, Shaofeng(朱绍峰)
Anhui Key Laboratory of Advanced Building Materials, Anhui University of Architecture,
Hefei, Anhui 230022, China
A novel mediator (Al/KF) has been developed and employed in the Barbier-type alkylations of various alde-
hydes and ketones with alkyl halide in water. The carbonyl compounds could be effectively converted into corre-
sponding homoallylic alcohol in good yields only when allyl bromides or substituted allyl bromides were used as
halides. Aromatic aldehydes could afford homoallylic alcohols in high yields, unfortunately, the allylation of aro-
matic aldehyde substituted by nitro- or amino-group could not proceed smoothly, and the allylation yields of ke-
tones and aliphatic carbonyl compounds were lower under the same condition. The diastereoselectivity and regiose-
letivity of the reaction have also been studied, the predominant products preferred the erythro- or anti-isomer in
dominant γ-adduct by using Al/KF mediated allylation of benzaldehydes with cinnamyl bromide and ethyl
4-bromo-2-butenoate in water.
Keywords aluminum, allylation reaction, fluoride salt, aqueous media
Introduction
der condition of nitrogen atmosphere.9f Because nano-
aluminum is easily oxidized to Al2O3, in practice, it is
inconvenient for nano-aluminum to be used for Bar-
bier-Grignard reaction in water.
The challenge here is to find ways to overcome the
well-known insolubility of aluminum oxide in water,
which has been so far restricting use of aluminum in
aqueous media. It has been reported that mercury could
corrode a thin film of Al2O3 to form aluminum amalgam
in water15a,15b and trace amount of fluoride anion in wa-
ter dramatically increased the corrosion of aluminum
metal.14b,15c,15d
Recently, there have been some reports on the use of
metal fluorides or a combination of complex and fluo-
ride anion for allylation of carbonyl compounds as aux-
iliaries in water.16
In continuation of our work on allylation of carbonyl
compounds with allyl bromide in aqueous media by
using aluminum powder, we draw our attention to the
possibility to use fluoride salt to activate aluminum
metal to implement allylation of carbonyl compounds in
water.
Barbier-Grignard reaction is one of the most impor-
tant reactions for the formation of carbon-carbon bond.
Recently, there has been a considerable interest in de-
veloping organometallic reactions in water of which
allylation of aldehydes and ketones to give homoallylic
alcohols has been regarded widely.1 This reaction has
been achieved by using metals such as Mn/Cu,2 Sn,3
Zn,4 Bi,5 In,6 Mg,7 Ga,8 Al,9 or organometallic com-
pounds such as diallylmercury, allylmercury bromide,10
palladium complexes,11 allyltributylstannanes12 and
tetraallylgermane.13
Previously indium and gallium subsequently were
reported to mediate Barbier-Grignard and pinacol cou-
ple type reactions in water.6,8 Aluminum locates in the
same group with indium and gallium in the periodic
table. Of these metals, aluminum is the most highlight-
ing metal used for pinacol coupling reaction in basic
aqueous media.14 However, it is very difficult to use
aluminum to mediate Barbier-Grignard type reactions as
indium and gallium in water. Maybe aluminum forms
readily a thin film of insoluble Al2O3, which can not be
dissolved in acidic aqueous solution but dissolved in
basic aqueous solution, and as an armor to prevent itself
from further Barbier-Grignard reaction of carbonyl
compounds with allylic halide in water or acidic solu-
tion.
Results and discussion
Our initial study was started by reacting benzalde-
hyde with allyl bromide in the presence of aluminum
under various conditions. The results are summarized in
Table 1.
We have reported that nano-aluminum could achieve
allylation of carbonyl compounds in aqueous media un-
*
E-mail: yuanshzh@mail.hf.ah.cn; Tel.: 0086-0551-3828100
Received June 30, 2009; revised October 23, 2009; accepted December 17, 2009.
578
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 578— 582

Allylation of Carbonyl Compounds
Table 1 Allylation of benzaldehyde with allyl bromide mediated by nano-Al under various conditions
Entry
Reaction media
H2O/2.0 mmol Al
Allylation yielda,b/%
Benzyl alcohol yielda,b/%
1c
2d
3
4
5
6
7
8
9
10
11
12
13
14d
—
77
—
—
—
54
62
79
75
41
43
87
86
83
—
11
—
—
—
23
17
9
13
33
39
7
0.5 mol•L－ 1 KF/2.0 mmol Al
0.5 mol•L－ 1 KCl/2.0 mmol Al
0.5 mol•L－ 1 KBr/2.0 mmol Al
0.5 mol•L－ 1 KI/2.0 mmol Al
0.5 mol•L－ 1 LiF/2.0 mmol Al
0.5 mol•L－ 1 NaF/2.0 mmol Al
0.5 mol•L－ 1 RbF/2.0 mmol Al
0.5 mol•L－ 1 CsF/2.0 mmol Al
0.5 mol•L－ 1 FeF3/2.0 mmol Al
0.5 mol•L－ 1 CuF2/2.0 mmol Al
1.0 mol•L－ 1 KF/2.0 mmol Al
2.0 mol•L－ 1 KF/2.0 mmol Al
1.0 mol•L－ 1 KF/2.0 mmol Al
9
12
a The isolated yields are reported. b The pure product was identified by IR, 1H, 13 C NMR and HRMS. c The quantities of solvents all were
5.0 mL and all reaction times are 18 h. d The reaction temperature was room temperature but Entry 14 at 40 ℃.
It was found that aluminum could not activate the
allylation in distilled water (Entry 1, Table 1). Compar-
ing the series KF, KCl, KBr and KI, only the addition of
KF led to allylation reaction (Entries 2— 5, Table 1).
Using the series of alkali metal fluoride salts under oth-
erwise identical reaction conditions, the allylation yields
were more similar to that of KF using RbF and CsF as
corrosive agent (Entries 8, 9, Table 1), but it declined
when LiF and NaF were used as additives (Entries 6, 7,
Table 1).
When the high valence fluoride salts such as FeF3,
CuF2 led to allylation reaction, the yields of benzyl al-
cohol were obviously increased as by-products (Entries
10, 11, Table 1). Interestingly, a higher concentration of
KF helped to increase yields of allylation reaction (En-
tries 12, 13, Table 1). This may be that ex＋cess KF read-
ily forms a K3[AlF6] complex with Al3 , which can
avoid producing suspension of insoluble Al(OH)3 to
cover aluminum powder to stop further allylation reac-
tion. However, raising reaction temperature has hardly
increased allylation yields (Entry 14, Table 1).
The benzaldehyde bearing a trifluoromethyl or
chloro group proceeded to give corresponding desired
products in higher yields (Entries 6— 8, Table 2). The
benzaldehyde bearing a methyl, methoxy, or methyl-
ene-dioxy group gave allylation products in lower yields
(Entries 2— 4, Table 2). This experimental result indi-
cated that the transition states of reaction may be elec-
tronegative. But the benzaldehyde bearing a p-nitro or
p-N,N-dimethylamino group gave rise to the formation
of benzyl alcohol almost in quantitative yields (Entries 5,
9, Table 2). Heteroaromatic aldehyde also proceeded
smoothly in good yield (Entry 11, Table 2). Acetophe-
none also gave the corresponding allylation product in
56% yield (Entry 12, Table 2). However, the most ali-
phatic aldehydes and ketones were not allylated effi-
ciently under the current conditions (Entries 13, 14, Ta-
ble 2).
Subsequently, Barbier-type alkylations were tested
by using the reaction of benzaldehyde with different
halides under above-mentioned condition. The results
are summarized in Table 3.
After a comprehensive survey of the reaction condi-
tions, it was found that allylation of benzaldehyde (1.0
mmol) with allyl bromide (1.6 mmol) could provide the
high yield of homoallylic alcohols by us－ing aluminum
powder (2.0 mmol) in aqueous 1.0 mol•L 1 KF at room
temperature. Subsequently, a variety of aldehydes and
ketones were examined using this allylation method
(Scheme 1). The results are listed in Table 2.
As shown in Table 3, no alkylation product was ob-
served when ethyl bromide and benzyl bromide were
used as reactants (Entries 1, 2, Table 3). Nevertheless,
Barbier-type alkylation was effective for the cinnamyl
bromide (Entry 3, Table 3).
In order to evaluate the regio- and stereoselectivity,
we studied the stereoselective reaction of the allylation
of benzaldehyde by using cinnamyl bromide and ethyl
4-bromo-2-butenoate in Al/KF (aq.). The results of the
regio- and stereoselectivities are presented in Table 4.
From Table 4, it was found that benzaldehyde could
be converted to the corresponding homoallylic alcohol
with high yields, regardless of the use of cinnamyl bro-
mide or ethyl 4-bromo-2-butenoate under this condition.
The predominant products preferred the erythro- or
anti-isomer in dominant γ-adduct (Entries 1, 2, Table 4).
The stereochemical assignments were made by com-
Scheme 1
a: R＝C6H5, R1＝H; b: R＝4-CH3C6H4, R1＝H; c: R＝4-CH3O6H4,
R1＝H; d: R＝3,4-CH2O2C6H3, R1＝H; e: R＝4-(CH3)2NC6H4, R1＝H;
f: R＝4-ClC6H4, R1＝H; g: R＝2-ClC6H4, R1＝H; h: R＝4-F3CC6H4,
R1＝H; i: R＝4-NO2C6H4, R1＝H; j: R＝β-naphthyl, R1＝H; k: R＝
2-furyl, R1＝H; m: R＝C6H5, R1＝CH3; n: R＝H, R1＝H; t: R＝
CH3CH2, R1＝CH3
Chin. J. Chem. 2010, 28, 578— 582
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
579

Yuan et al.
FULL PAPER
Table 2 Allylation reactions mediated by Al/KF in water
Entry
1
Substrate
Product (Yielda,b/%)
Entry
Substrate
Product (Yielda,b/%)
3a (87)
8
3h (95)
2
3
3b (71)
9
3i (— )
3c (67)
3d (65)
10
3j (61)
4
5
6
7
11
12
13
14
3k (63)
3m (56)
3n (42)
3t (37)
3e (—
)
3f (93)
3g (89)
a Products were identified by IR, 1H NMR, 13 C NMR and HRMS. b Isolated yields.
Table 3 Barbier-type alkylations of benzaldehyde mediated by Al/KF (aq.) with different halides
Entry
Halide
CH3CH2Br
Time/h
72
Yielda,b/%
Reaction condition
1
2
3
—
—
73
Al/1.0 mol•L－ 1 KF/r.t.
Al/1.0 mol•L－ 1 KF/r.t.
Al/1.0 mol•L－ 1 KF/r.t.
PhCH2Br
72
PhCH＝ CHCH2Br
18
a Identified by IR, 1H NMR, 13 C NMR and HRMS. b Isolated yields.
Table 4 Regio- and stereo-selectivities in the Al/KF-mediated allylation of reactions
3u: R＝Ph, 3v: R＝CO2C2H5
Yielda/%
Entry
Halide
Reaction condition
α (Z∶ E)b
16 (69∶ 31)
17 (67∶ 33)
γ (syn∶ anti)/(erythro/threo)b
57 (73∶ 27)/(erythro/threo)
64 (41∶ 59)/(syn/anti)
1
2
Al/1.0 mol•L－ 1 KF/r.t./18 h
Al/1.0 mol•L－ 1 KF/r.t./18 h
a Isolated yield. b The ratio of α to γ was determined by 1 H NMR.
1
parison of H NMR spectra with those of the same or
[HP5890 (II)/HP 5972, EI] data were obtained at the
Center of Analytical Configuration of University of
Science and Technology of China. Flash chroma-
tographic sheets employed were purchased from Anhui
Liangchen Silicon Material Co. Ltd. and all materials
were purchased from Aldrich and used directly as re-
ceived.
similar compounds (3u,3c,4c,17 3v8a,18).
Experimental
All IR (Perkin-Elmer, 2000 FTIR), 1H NMR (CDCl3,
500 MHz), 13 C NMR (CDCl3, 125.7 MHz) and MS-GC
580
www.cjc.wiley-vch.de
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 578— 582

Allylation of Carbonyl Compounds
General allylation reaction procedures
8632.
(b) Paquette, L. A.; Bennett, G. D.; Chhatriwalla, A.; Isaac,
M. J. Org. Chem. 1997, 62, 3370.
(a) Nokami, J.; Otera, J.; Sudo, T. Organometallics 1983, 2,
191.
(b) Nokami, J.; Otera, J.; Sudo, T.; Okawara, R. Chem. Lett.
1984, 869.
(c) Tan, X. H.; Hou, Y. Q.; Huang, C.; Liu, L.; Guo, Q. X.
Tetrahedron 2004, 60, 6129.
(d) Ricardo, L.; Guimarães, R.; Lima, D.; Barros, M. E.;
Cavalcanti, L.; Hallwass, F.; Navarro, M.; Bieber, L.;
Malvestiti, I. Molecules 2007, 12, 2089.
(a) Petrier, C.; Luche, J. L. J. Org. Chem. 1985, 50, 910.
(b) Petrier, C.; Einhorn, J.; Luche, J. C. Tetrahedron Lett.
1985, 26, 1445.
(c) Sjöholm, R.; Rairama, R. L.; Ahonen, M. C. J. Chem.
Soc., Chem. Commun. 1994, 1217.
(a) Wada, M.; Ohki, H.; Akiba, K. Y. Bull. Chem. Soc. Jpn.
1990, 63, 1738.
(b) Matsumura, N.; Doi, T.; Mishima, K.; Kitagawa, Y.;
Okumura, Y.; Mizuno, K. ITE Lett., Batt. New Tech. Med.
2003, 4, 473.
(a) Li, C. J.; Chan, T. H. Tetrahedron Lett. 1991, 32, 7017.
(b) Chan, T. H.; Li, C. J. J. Chem. Soc., Chem. Commun.
1992, 747.
(a) Zhang, W. C.; Li, C. J. J. Org. Chem. 1999, 64, 3230.
(b) Wada, M.; Fukuma, T.; Morioka, M.; Takahashi, T.;
Miyoshi, N. Tetrahedron Lett. 1997, 38, 8045.
(a) Wang, Z. Y.; Yuan, S. Z.; Li, C. J. Tetrahedron Lett.
2002, 43, 5097.
(b) Takai, K.; Ikawa, Y. Org. Lett. 2002, 4, 1727.
(c) Wang, Z. Y.; Yuan, S. Z.; Zha, Z. G.; Zhang, Z. D. Chin.
J. Chem. 2003, 21, 1231.
(a) Tanaka, H.; Yamashita, S.; Hamatani, T.; Ikemoto, Y.;
Torii, S. Synth. Commun. 1987, 17, 789.
(b) Wada, M.; Ohki, H.; Akiba, K. Y. J. Chem. Soc., Chem.
Commun. 1987, 708.
(c) Tanaka, H.; Nakahata, S.; Watanabe, H.; Zhao, J.; Ku-
roboshi, M.; Torii, S. Inorg. Chim. Acta 1999, 296, 204.
(d) Takai, K.; Ikawa, Y. Org. Lett. 2002, 4, 1727.
(e) Shen, K. H.; Yao, C. F. J. Org. Chem. 2006, 71, 3980.
(f) Yuan, S. Z.; Liu, J. Chin. J. Chem. 2008, 26, 804.
To a stirred mixture of carbonyl compounds (1.0
mmol), allyl bromide (1.6 mmol) and Al powder (2.0
mmol) at room temperature was gradually added 1.0
3
mol•L－ KF solution (10 mL) for 18 h. After the reac-
1
tion, insoluble materials were filtered off and the filtrate
was extracted with dichloromethane (20 mL× 3). The
extract was washed with water, dried over anhydrous
MgSO4, and then evaporated in vacuo to give a residue.
The pure products were obtained by flash chromatogra-
phy on silica gel eluting with petroleum ether/EtOAc
1
(V∶ V＝ 4∶ 1), and identified by IR, H, 13 C NMR and
4
5
HRMS. All compounds obtained were consistent with
authentic ones in literature.3c,4c,8a,9f,16-18
1
1,2-Diphenyl-3-buten-1-ol (3u): H NMR (CDCl3,
400 MHz) δ: erythro isomers: 1.65 (brs, 1H), 3.81—
3.89 (m, 1H), 4.63 (d, J＝ 5.86 Hz, 1H), 4.97— 5.08 (m,
2H), 5.61— 5.84 (m, 1H), 7.09— 7.38 (m, 10H); threo
isomers: 1.93 (brs, 1H), 3.81— 3.89 (m, 1H), 4.37 (d,
J＝ 7.61 Hz, 1H), 5.16— 5.29 (m, 2H), 5.61— 5.84 (m,
1H), 7.09— 7.38 (m, 10H); 13C NMR (CDCl3, 100 MHz)
δ: erythro isomers: 44.7, 77.0, 115.3, 126.7, 127.4,
128.1, 128.3, 128.9, 129.1, 138.2, 140.3, 141.6; anti
isomers: 46.3, 77.1, 116.2, 126.9, 127.7, 128.3, 128.6,
129.3, 129.8, 138.9, 140.7, 142.1; IR (film) ν: 3381.2,
3075.3, 1647.5 cm － 1; HRMS calcd for C16H16O
224.1042, found 224.1046.
6
7
8
Ethyl 2-(α-hydroxybenzyl)-3-butenoate (3v): 1H
NMR (CDCl3, 400 MHz) δ: syn isomers: 1.28 (t, J＝
7.01 Hz, 3H), 2.47 (brs, 1H), 3.32— 3.54 (m, 1H), 4.21
(q, J＝ 7.32 Hz, 2H), 4.71 (d, J＝ 5.57 Hz, 1H), 4.92—
5.03 (m, 2H), 5.93— 6.01 (m, 1H), 7.36— 7.64 (m, 5H);
threo isomers: 1.28 (t, J＝ 7.01 Hz, 3H), 2.47 (brs, 1H),
3.32— 3.54 (m, 1H), 4.21 (q, J＝ 7.32 Hz, 2H), 4.35 (d,
J＝ 7.53 Hz, 1H), 5.21— 5.35 (m, 2H), 5.93— 6.01 (m,
1H), 7.36— 7.64 (m, 5H); 13 C NMR (CDCl3, 100 MHz)
δ: erythro isomers: 14.20, 42.7, 63.9, 76.0, 115.3, 126.7,
127.4, 128.1, 140.3, 141.6, 171.7; anti isomers: 16.3,
46.3, 67.1, 77.8, 116.2, 126.9, 127.7, 128.6, 142.3,
146.9, 174.2; IR (film) ν: 3385.1, 3072.1, 1687.5,
9
－
1
1573.2, 1293.1, 708.2 cm ; HRMS calcd for C13H16O3
220.1043, found 220.1057.
10 Loh, T. P.; Xu, J. Tetrahedron Lett. 1999, 40, 2431.
11 Mina Mazzeo, M.; Lamberti, M.; Massa, M.; Scettri, A.;
Pellecchia, C.; Peters, J. Organometallics 2008, 27, 5741.
12 Akiyama, T.; Iwai, J. Tetrahedron Lett. 1997, 38, 853.
13 Annunziata, R.; Benaglia, M.; Cinqnini, M.; Raimondi, L.
Eur. J. Org. Chem. 1999, 3369.
14 (a) Mecairova, M.; Toma, S. Green Chem. 1999, 1, 257.
(b) Li, L. H.; Chan, T. H. Org. Lett. 2000, 2, 1129.
(c) Mecairova, M.; Toma, S.; Babiak, P. Chem. Papers
2001, 55, 302.
Conclusion
In conclusion, this study demonstrated a novel car-
bonyl allylation reaction mediated by aluminum powder
in aqueous KF. The reaction is very efficient and appli-
cable to most aldehydes and ketones. Since aluminum
powder is cheap and easy to handle, this method could
be more valuable for practical application.
(d) Yuan, S. Z.; Wang, Z. Y.; Li, Z. Chin. J. Chem. 2006, 24,
141.
15 (a) Fieser, M.; Fieser, F. L. Reagents for Organic Synthesis,
John Wiley & Sons, New York, 1975, p. 9.
References
1
Anastas, P.; Williamson, T. C. Green Chemistry: Frontiers
in Benign Chemical Synthesis and Processing, Oxford Uni-
versity Press, New York, 1988.
(b) Troyansky, E. I. The Encyclopedia of Reagent for Or-
ganic Synthesis, Ed.: Paquette, L. A., John Wiley & Sons,
2
(a) Li, C. J.; Meng, Y.; Yi, X. H. J. Org. Chem. 1997, 62,
Chin. J. Chem. 2010, 28, 578— 582
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
581

Yuan et al.
FULL PAPER
Chichester, 1995, p. 150.
(c) Tennakone, K.; Wickramanyaka, S. Nature 1987, 325,
202.
(d) Yamamoto, H.; Wadamoto, M. Chem. Asian J. 2007, 2,
692.
17 (a) Coxon, J. M.; Simpson, G. W.; Steel, P. J.; Trenerry, V.
C. Aust. J. Chem. 1984, 37, 65.
(b) Uneyama, K.; Nanbu, H.; Torü, S. Tetrahedron Lett.
1986, 27, 2395.
18 (a) Imai, T.; Nishida, S. Synthesis 1993, 395.
(b) Annunziata, R.; Benaglia, M.; Cinqnini, M.; Raimondi,
L. Eur. J. Org. Chem. 1999, 3369.
(d) Valand, T.; Nilsson, G. Corros. Sci. 1977, 17, 449.
16 (a) Li, L. H.; Chan, T. H. Tetrahedron Lett. 2000, 41, 5009.
(b) Wadamoto, M.; Ozasa, N.; Yanagisawa, A.; Yamamoto,
H. J. Org. Chem. 2003, 68, 5593.
(c) Wadamoto, M.; Yamamoto, H. J. Am. Chem. Soc. 2005,
127, 14556.
(E0906302 Zhao, C.; Dong, H.)
582
www.cjc.wiley-vch.de
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 578— 582