Solvent- and catalyst-free gem-bisallylation of carboxylic acid derivatives with allylzinc bromide

Article abstract of DOI:10.1016/j.tetlet.2008.07.097

A rapid and efficient procedure for the solvent-free synthesis of gem-bisallylation products has been achieved by allylzinc bromide with carboxylic acid derivatives in the absence of any catalysts at room temperature.

Full text of DOI:10.1016/j.tetlet.2008.07.097

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Tetrahedron Letters 49 (2008) 5697–5699
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Tetrahedron Letters
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Solvent- and catalyst-free gem-bisallylation of carboxylic acid
derivatives with allylzinc bromide
Yu-Juan Wei a, Heng Ren a, Jin-Xian Wang a,b,
*
a Institute of Chemistry, Department of Chemistry, Northwest Normal University, 967 Anning Road (E), Lanzhou 730070, PR China
b State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A rapid and efficient procedure for the solvent-free synthesis of gem-bisallylation products has been
achieved by allylzinc bromide with carboxylic acid derivatives in the absence of any catalysts at room
temperature.
Received 14 December 2007
Revised 17 July 2008
Accepted 18 July 2008
Available online 23 July 2008
Ó 2008 Elsevier Ltd. All rights reserved.
The addition reaction of organometallics and carbonyl com-
pounds provides a fundamental methodology in synthetic organic
chemistry.1 Monoallylation and gem-bisallylation typically give
homoallylic alcohol and bisallyl alkyl carbinol, which have poten-
tial for use in the synthesis of variety of compounds including
hydroxyl lactone and spirolactone.2 Various carbonyl compounds
are widely used as convenient starting materials for such transfor-
mations. Usually, homoallylic alcohols were obtained utilizing
these methods, but little attention has been paid to the geminal
bisallylation of carbonyl compounds.3 The bisallylation reaction
has been just developed in recent 10 years, and different methods
have been developed based on the use of a variety of metals such
as In,4 Sm,5 Zn,6 and Al.7
Organozinc reagents have been known for more than 150
years.8 However, their applications in organic synthesis were lim-
ited to very specific reactions due to their moderate reactivity.
These reagents were soon replaced by the more reactive organo-
magnesium and organolithium reagents which found broad appli-
cations in organic synthesis. However, it became clear that this
high reactivity has some drawbacks, such as low chemoselectivity
and only allowing R groups bearing relatively few functionalities. It
was noticed that organozinc reagents could be easily prepared and
have higher functional group compatibility in comparison with
organolithium and Grignard reagents. Furthermore, the low reac-
tivity of organozinc reagents could be increased by adding transi-
tion metal catalyst.9–11 Today, organozinc compounds are one
of the most useful organometallic reagents. The applications of
organozinc compounds range from asymmetric synthesis, prepara-
tion of biologically relevant molecules, and new materials in com-
binatorial chemistry.
The elimination of volatile organic solvents in organic syntheses
is the most important goal in ‘green’ chemistry. Recently, solvent-
free reactions have received increasing attentions because of the
advantages: short reaction time, high yield, low costs, reduced pol-
lution, and simplicity in process and handling.12 As environmen-
tally friendly ‘green’ synthesis has become more important,
chemists have been searching for solvent-free reactions under mild
conditions.13
Research work on organozinc halides has been performed in our
laboratory over the past few years.14 With our increasing interests
in efficient, economic, and environmentally friendly reactions, we
have explored the reaction of organozinc reagents under solvent-
free conditions. In this Letter, we wish to report a convenient, envi-
ronmentally friendly, and efficient gem-bisallylation of acid chlo-
ride, acid anhydride, and ester using allylzinc bromide under
solvent-free conditions.
The gem-bisallylation reaction of benzoyl chloride (1a) and
allylzinc bromide (2) was selected as model reaction for optimizing
reaction conditions. The results are summarized in Table 1. It was
found that the best result for formation of 4-phenylhepta-1,6-dien-
4-ol (3a) could be obtained when the relative molar ratio of 2:1a
was increased to 4:1 (Table 1, entry 3). Although 3a could be ob-
tained in the presence of THF as solvent, the reaction proceeded
more smoothly and efficiently under solvent-free conditions. It is
evident that the molar ratio of 4 (2/1a) is essential for obtaining
a maximum yield under solvent-free conditions.
With these encouraging results listed in Table 1, we investi-
gated the gem-bisallylation reactions further with a number of car-
boxylic acid derivatives including acid chlorides, carboxylic esters,
and acid anhydrides under the conditions established above. The
results are summarized in Table 2.
From the results shown in Table 2, it can be seen that most of
the reactions proceeded smoothly at room temperature in good
to excellent yields. In general, bisallylation of aromatic acid
* Corresponding author. Tel.: +86 931 7970567; fax: +86 931 7768159.
E-mail address: wangjx@nwnu.edu.cn (J.-X. Wang).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.07.097

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5698
Y.-J. Wei et al. / Tetrahedron Letters 49 (2008) 5697–5699
Table 2 (continued)
Table 1
Optimized conditions via gem-bisallylation reaction of 1a and 2a
Entry
R
X
Productb
Yieldc (%)
70
O
OH
8
CH3
Cl
HO
N2
3h
ZnBr
+
H3C
Cl
r.t. 30 min
2
1a
3a
OH
OH
Entry
Solvent
Molar ratio of 2/1a
Yield of 3ab (%)
9
10
11
C2H5
BrCH2
Ph
Cl
3i
74
81
88
C2H5
1
2
3
4
5
6
7
8
None
None
None
THF
CH2Cl2
C6H6
Et2O
2
3
4
4
4
4
4
4
68
87
96
91
96
95
92
0
Br
Br
3j
DMF
a
OH
Reaction conditions: at room temperature under nitrogen for 30 min.
Isolated yield.
b
OCH3
3a
Table 2
gem-Bisallylation reaction of derivatives of carboxylic acids with allylzinc bromidea
OH
H3C
12
13
m-CH3–C6H4
OC2H5
3e
92
68
O
solvent-free
r.t. 30 min
R
ZnBr
+
R
X
HO
3
2
1
OH
R= aryl, alkyl
X= Cl,Br,OR', OCOR'
Ph
OCH2Ph
3a
Entry
R
X
Productb
Yieldc (%)
96
OH
OH
1
C6H5
Cl
3a
Br
Br
14
15
16
BrCH2
BrCH2
CH2CH
OCH3
OC2H5
OCH3
3j
92
89
68
OH
OH
2
p-Cl–C6H5
Cl
3b
83 (91)d
3j
Cl
OH
Cl
OH
3k
3k
3
4
5
6
o-Cl–C6H5
Cl
Cl
Cl
Cl
3c
88
77
92
82
OH
OH
17
18
CH2CH
OC2H5
OCOPh
66
90
p-CH3O–C6H4
m-CH3–C6H4
C6H5–CH'CH
3d
H3CO
H3C
OH
OH
Ph
3a
3e
3f
O
OH
19
3l
70
O
O
O
O
a
Reaction conditions: carboxylic acid derivatives (2.0 mmol), allylzinc bromide
(8.0 mmol), solvent-free, at room temperature under nitrogen for 30 min.
HO
b
All products were characterized by IR, 1H NMR, 13C NMR, and MS.
O
7
2-Furyl
Cl
3g
92
c
Isolated yield.
d
The reaction temperature was reduced with a ice-water bath (about at 0–5 °C).

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5699
7472; (d) Ranu, B. C.; Majee, A.; Das, A. R. Tetrahedron Lett. 1995, 36, 4885; (e)
Hamann-Gaudinet, B.; Namy, J.-L.; Kagan, H. B. Tetrahedron Lett. 1997, 38, 6585.
2. (a) Bardshiri, E.; Simpson, T. J.; Scott, A. I.; Shishido, K. J. J. Chem. Soc., Perkin
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4. Yoo, J.; Oh, K. E.; Keum, G.; Kang, S. B.; Kim, Y. Polyhedron 2000, 19, 549.
5. Li, Z.; Zhang, Y. Tetrahedron 2002, 58, 5301.
chlorides (Table 2, entries 1–7) gave the corresponding products in
good to excellent yields under solvent-free conditions. Aliphatic
acid chlorides were also bisallylated smoothly under the same
conditions in good yields (Table 2, entries 8–10). It was concluded
that electron-withdrawing or donating groups on the aromatic ring
of aromatic acid chlorides did not seem to affect the reaction sig-
nificantly in the yield of products. But the position of the substitu-
ent on the phenyl ring affects the product yields. For example,
2-chlorobenzoylate (Table 2, entry 3) and 4-chlorobenzoylate
(Table 2, entry 2) afforded allylated products in the yield of 88
and 75%, respectively. And the yields of the gem-bisallylation
reaction of acid chlorides, carboxylic esters, and acid anhydrides
decrease in sequence. For example, benzoyl chloride, benzoic
anhydride, and methyl benzoate reacted with allylzinc bromide
to give the same gem-bisallylated products of 3a in 96%, 90%, and
88% yields, respectively(Table 2, entries 1, 11, 18). Furthermore,
allylzinc bromide would react with cyclic anhydrides such as iso-
benzofuran-1,3-dione to generate the corresponding gem-bisally-
lated esters, and the product yield is 70% (Table 2, entry 19).
In conclusion, we have developed a novel and simple procedure
for the gem-bisallylation of carboxylic acid derivatives using allyl-
zinc bromide under solvent-free and catalyst-free conditions at
room temperature.15 The reaction here has the following advanta-
ges: milder conditions, shorter reaction times, environmentally
benign, and high yield.
6. Ishino, Y.; Mihara, M.; Kageyama, M. Tetrahedron Lett. 2002, 43, 6601.
7. Shen, K-H.; Kuo, C.-W.; Yao, C.-F. Tetrahedron Lett. 2007, 48, 6348.
8. Frankland, E. Liebigs Ann. 1849, 71, 171.
9. Negishi, E. Acc. Chem. Res. 1982, 15, 340.
10. (a) Knochel, P.; Yeh, M. C. P.; Berk, S. C.; Talbert, J. J. Org. Chem. 1988, 53, 2390;
(b) Berk, S. C.; Yeh, M. C. P.; Jeong, N.; Knochel, P. Organometallics 1990, 9, 3053.
11. (a) Knochel, P.; Perea, J. J. A.; Jones, P. Tetrahedron 1998, 54, 8275; (b) Men, X.;
Wang, K.; Wang, J.-X.; Shi, X. Chin. J. Org. Chem. 2004, 24, 825.
12. Rodriguez, B.; Bruckmann, A.; Bold, C. Adv. Synth. Catal. 2007, 349, 2213.
13. Tanaka, K.; Toda, F. Chem. Rev. 2000, 100, 1025.
14. (a) Wang, J.-X.; Fu, Y.; Hu, Y. L. Angew. Chem., Int. Ed. 2002, 41, 2757; (b) Wang,
J.-X.; Wang, K.; Zhao, L.; Li, H.; Fu, Y.; Hu, Y. L. Adv. Synth. Catal. 2006, 348, 1262;
(c) Hu, Y. L.; Yu, J. H.; Yang, S.; Wang, J.-X. Synlett 1998, 1213; (d) Huang, D.;
Wang, J.-X. Synlett 2007, 2272.
15. General experimental procedure for gem-bisallylation of carboxylic acid
derivatives: Organozinc halides RZnX (8.0 mmol) were prepared according to
Knochel’s procedure.10 The solvent (THF) of the RZnX was removed in vacuo,
then carboxylic acid derivatives (2.0 mmol) were added slowly, and the
resulting mixture stirred for 30 min. After complete conversion as indicated by
TLC, the reaction mixture was quenched with aqueous saturated NH4Cl (10 mL)
and extracted with Et2O (3 Â 10 mL). The combined organic extracts were
dried over anhydrous MgSO4 and concentrated. The resulting product was
purified by column chromatograph on silica gel (petroleum/ethyl acetate 40:1)
to afford the pure product. Typical spectra data are as follows: 4-Phenylhepta-
1,6-dien-4-ol (3a) IR (m
/cmÀ1): 3356, 3074, 2924, 1639, 1441, 1340, 1053,
1035, 998, 918; 1H NMR (400 MHz, CDCl3, TMS): d = 7.42–7.22 (m, 5H), 5.66–
5.56 (m, 2H), 5.13–5.07 (m, 4H), 2.72–2.49 (m, 4H), 2.09 (s, 1H), 13C NMR
(100 MHz, CDCl3): d = 133.4, 128.1, 128.1, 126.6, 125.2, 119.2, 75.0, 46.8; EI-MS
(m/z, %): 147 (M+À41, 10.13), 105 (100.00), 77 (53.99), 51 (18.75), 41 (28.91),
Acknowledgments
The work was supported by the Natural Science Foundation of
China (Grants 20272047 and 20572086), the Gansu Natural Sci-
ence Foundation of China (3ZS051-A25-001), and Key Laboratory
of Eco-Environment-Related Polymer Material (Northwest Normal
University), Ministry of Education of China.
39 (28.07). 3,3-Diallylisobenzofuran-1(3H)-one (3l) IR (m
/cmÀ1): 3508, 3079,
2911, 1726, 1642, 1466, 1286, 1080, 997, 923; 1H NMR (400 MHz, CDCl3, TMS):
d = 7.87–7.27 (m, 4H), 5.60–5.50 (m, 2H), 5.06 (t, J = 8.0 Hz, 4H), 2.79–2.64 (m,
4H); 13C NMR (100 MHz, CDCl3): d = 169.8, 151.5, 133.8, 130.6, 129.0, 126.8,
125.6, 121.5, 120.3, 88.2, 42.6; EI-MS (m/z, %): 215 (M++1, 0.48), 214 (M+, 6.2),
173 (100.00), 131 (1.58), 117 (80.76), 76 (38.03), 39 (53.32).
References and notes
1. (a) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207; (b) Li, C. J. Tetrahedron
1996, 52, 5643; (c) Yi, X.-H.; Meng, Y.; Hua, X.-G.; Li, C.-J. J. Org. Chem. 1998, 63,