An efficient of Grignard-type procedure for the preparation of gem-diallylated compound

Article abstract of DOI:10.1016/j.tetlet.2007.07.008

An efficient and a new procedure for the conversion of various carboxylic acid derivatives into the corresponding gem-diallylated compound under mild reaction condition has been developed. The triallylaluminum mediated Grignard-type addition of carboxylic acid derivative was utilized as a key operation to affect the transformation. The procedure is operationally simple, giving good to excellent product yields for a broad range of substrates. The chemoselectivity and regioselectivity of triallylaluminum were also demonstrated.

Full text of DOI:10.1016/j.tetlet.2007.07.008

Tetrahedron Letters 48 (2007) 6348–6351
An efficient of Grignard-type procedure for the preparation of
gem-diallylated compound
Kao-Hsien Shen, Chun-Wei Kuo and Ching-Fa Yao*
Department of Chemistry, National Taiwan Normal University 88, Sec. 4, Tingchow Road, Taipei 116, Taiwan, ROC
Received 17 January 2007; revised 2 July 2007; accepted 3 July 2007
Available online 10 July 2007
Abstract—An efficient and a new procedure for the conversion of various carboxylic acid derivatives into the corresponding gem-
diallylated compound under mild reaction condition has been developed. The triallylaluminum mediated Grignard-type addition of
carboxylic acid derivative was utilized as a key operation to affect the transformation. The procedure is operationally simple, giving
good to excellent product yields for a broad range of substrates. The chemoselectivity and regioselectivity of triallylaluminum were
also demonstrated.
ꢀ 2007 Elsevier Ltd. All rights reserved.
The allylation of carbonyl derivative is of great interest
in carbon–carbon bond formation, due to the versatil-
ity of homoallylic alcohol as synthetic intermediate.1
Monoallylation and gem-diallylation typically give
homoallylic alcohol and diallyl alkyl carbinol, which
have potential for the use in the synthesis of variety of
compounds, including hydroxyl lactone and spirolac-
tone.2 Different types of metal including In, Sm, Mg,
Zn, and Si have been used for this purpose.3 Reports
of the gem-diallylation of the derivative of carboxylic
acid using organoaluminum reagent are relatively rare.
It has been reported that aldehyde, ketone, and imine
can be efficiently allylated in the presence of catalytic
amount of a metal salt, such as PbBr2 and TiCl4, where-
in aluminum acts as an electron pool and the metal salt
functions as an electron transfer catalyst.4 However,
gem-diallylation reaction of the derivative of carboxylic
acid, especially acyl azide, has not been investigated in
great detail.5 It is noteworthy that, in a study of the
reaction of organometallic compound with iminoether,
organoaluminum compound was reported to react, but
only a few organoaluminum compound was examined
and only the ester derivative were tested as a reactant.6
As a result, based on the available data it is difficult to
evaluate the utility of the reaction with respect to reac-
tion of other carboxylic acid derivatives. Thus, it would
be desirable to develop an efficient method for the gem-
diallylation of a wide variety of substrates with allyl-
aluminum compound in a Grignard-type addition, since
aluminum is an inexpensive and convenient alternative
to conventionally used metal, such as samarium and sil-
icon. In this Letter, we wish to report on a convenient
and an efficient procedure for the gem-diallylation of
acid chloride, acid anhydride, acid azide, and ester using
triallylaluminum 1 in excellent to good yields.
Allylaluminum reagents are typically prepared by cou-
pling a commercially available organoaluminum chlo-
ride such as Me2AlCl with an appropriate Grignard or
lithium regent.7 However, we used a different method
for the preparation of triallylaluminum 1, following a
procedure reported in the literature.8,9 Triallylaluminum
was prepared by reacting allyl bromide and pure elemen-
tal Al in refluxing ether, followed by the concentration
of the reaction mixture (Scheme 1). We previously
reported that triallylaluminum reacts with aldehydes,
ketones, aldimines and ketimines in excellent yields.10
Herein, we report on the efficient gem-diallylation of a
variety of carboxylic acid derivatives with triallylalumi-
num 1 in ether solution, to yield various 4-hydroxy-
penta-1,6-dienes 3 (Scheme 2).
In a preliminary experiment, benzoyl chloride was
reacted with triallylaluminum (0.9 mmol) in anhydrous
ether
2 Al
AlBr3
(CH2=CHCH2)3Al
+
+
3 CH2=CHCH2Br
reflux
1
*
Corresponding author. Tel./fax: +886
cheyaocf@scc.ntnu.edu.tw
2 2930 9092; e-mail:
Scheme 1.
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.07.008

K.-H. Shen et al. / Tetrahedron Letters 48 (2007) 6348–6351
6349
Table 2. Reaction of derivates of carboxylic acids with triallylalumi-
num 1 to generate gem-bisallylated alcohols 3a
O
HO
R
ether
20 oC, 30 min
(CH2=CHCH2)3Al
+
R
X
OH
O
ether
20 oC, 30 min
1
2
R1
(CH2=CHCH2)3Al
+
R1
X
3
R = aryl, alkyl
1
2
3
X = Cl, OR', OCOR', N3
Entry
2
R1
Ph
4-ClC6H4
2-ClC6H4
Benzyl
Et
X
3
Yieldsb (%)
Scheme 2.
1
2
3
4
5
6
7
2a
2b
2c
2d
2e
2f
Cl
Cl
Cl
Cl
Cl
Cl
Cl
3a
97
98
97
98
98
94
92
3b
3c
3d
3e
3f
ether at 20 ꢁC, to give the corresponding gem-diallyl-
ation product in 60% yield after 30 min. In order to
increase the product yield, we gradually increased the
amount of triallylaluminum and the results are shown
in Table 1. From Table 1, it is evident that 1.2 mmol
of triallylaluminum is essential for obtaining a maxi-
mum yield.
1-Adamantyl
2-Thienyl
2g
3g
8
2h
3h
98
CH2COCl
S
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
2i
Ph
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OC6H5
OCOCH3
OCOPh
OCOPr
OCOPri
N3
3a
3i
98
98
96
98
97
98
98
91
98
96
98
98
98
98
81
88
98
88
92
2j
4-MeC6H4
2-MeC6H4
4-ClC6H4
2-ClC6H4
Benzyl
2-Thienyl
Pr
CH3
t-Bu
Ph
CH3
Ph
Pr
i-Pr
Ph
4-ClC6H4
Benzyl
1-Adamantyl
With this encouraging result in hand, we then investi-
gated other derivatives of carboxylic acids including acid
chlorides, carboxylic esters, acid anhydrides, and acyl
azides under the optimized conditions and the results
are summarized in Table 2. The corresponding gem-di-
allylated products are produced in good to excellent
yields, starting from a relatively wide variety of deriva-
tives. Both aromatic and aliphatic substrates are con-
verted smoothly to the corresponding gem-diallylated
products in good to excellent yields.
2k
2l
3j
3b
3c
3d
3g
3k
3l
2m
2n
2o
2p
2q
2r
3m
3a
3l
2s
2t
2u
2v
2w
2x
2y
2z
2aa
3a
3k
3n
3a
3b
3d
3f
Both aromatic and aliphatic substrates were converted
to the corresponding diallyl alkyl carbinols in excellent
yields. The results clearly show that a substituent on
the phenyl ring, whether electron-donating or electron-
withdrawing, had almost no influence on the reactions.
Further, the position of the substituent on the phenyl
ring does not affect the product yields. For example, 4-
methylbenzoylate 2j (entry 10) and 4-chlorobenzoylate
2l (entry 12) afforded allylated products in excellent
yields. Similarly, the use of the corresponding 2-substi-
tuted benzoyl chloride 2c (entry 3) and 2-substituted
benzoylate 2k and 2m (entries 11 and 13) also resulted
in excellent yields. Sterically hindered acid anhydrides
such as methyl pivalate 2r (entry 18) and isobutyric
anhydride 2w (entry 23) also afforded good yields of
products.
N3
N3
N3
28
2ab
3h
84
CH2CON3
S
a All reactions were carried out with substrate (1.0 mmol) and tri-
allylaluminum (1.2 mmol) in ether (3 mL) at 20 ꢁC under nitrogen for
30 min.
b Isolated yields for pure products.
obtained with 1-adamantanecarbonyl chloride 2f (entry
6) and 1-adamantanecarbonyl azide 2aa (entry 27) dem-
onstrates the versatile nature of triallylaluminum as an
efficient gem-allylating agent for a wide range of sub-
strates and these types of sterically rigid structures are
helpful in studying face selectivity.12
It is noteworthy that this is the first example of the gem-
diallylation of 1-adamantanecarbonyl chloride and
azide with an organometallic reagent. The higher yield
As above, triallylaluminum has been employed with car-
boxylic esters to give the corresponding gem-diallyl alkyl
carbinols. Moreover, this reagent would react with lac-
tones such as c-butylactone 4 and d-valerlactone 5 to
give the corresponding gem-diallyl alkyl carbinols 6
and 7 in 81% and 84% yields, respectively (Table 3,
entries 1 and 2). Furthermore, this reagent would react
with cyclic anhydrides such as succinic anhydride 8
and glutaric anhydrides 9 to generate the corresponding
gem-diallylated esters in good yields, and the product
yields are 94% and 71%, respectively (Table 3, entries
3 and 4).
Table 1. Effect of the loading of triallylaluminum in a reaction with
benzoyl chloridea
O
OH
ether
20 oC, 30 min
(CH2=CHCH2)3Al
+
Ph
Ph
Cl
1
2a
3a
Entry
1
3ab (%)
1
2
3
0.9
1.0
1.2
60
72
97
a All reactions were carried out with benzoyl chloride (1.0 mmol), ether
(3 mL) and triallylaluminum at 20 ꢁC under nitrogen for 30 min.
b Isolated yield for pure products.
The regioselectivity of triallylaluminum was confirmed
by extending the scope of this reagent to cinnamoyl

6350
K.-H. Shen et al. / Tetrahedron Letters 48 (2007) 6348–6351
Table 3. Reaction of derivates of carboxylic acids with triallylaluminum 1 to generate gem-diallyl alkyl carbinols
Entrya
Substrate
Product
Yieldsb (%)
1
2
4 n = 0
5 n = 1
6
7
81
84
n
HO
HO
O
O
O
n
n
n
3
4
8 n = 0
9 n = 1
10
11
94
71
O
R
O
O
O
5
6
7
8
12 R = Ph, X = Cl
13 R = Ph, X = N3
14 R = Ph, X = OCH3
15 R = CH3, X = OCH3
16
16
16
17
98
96
92
81
O
HO
R
X
a All reactions were carried out with substrate (1.0 mmol) and triallylaluminum (1.2 mmol) in THF (3 mL) at 20 ꢁC under nitrogen for 30 min.
b Isolated yields for pure products.
derivatives such as cinnamoyl chloride 12, cinnamoyl
azide 13, and methyl cinnamate 14 to generate the cor-
responding gem-diallyl alkyl carbinols in excellent yields
(98%, 96% and 92%). The triallylaluminum reagent is
also shown chemoselective when methyl crotonate 15
was used as a substrate, only the 1,2-addition product
was obtained selectively, and no 1,4-addition product
was detected (Table 3, entries 8).
ployed. To the best of our knowledge, this is the first re-
port of the use of triallylaluminum as a reagent for the
gem-diallylation of acid chlorides, acid anhydrides,
and acyl azides. Because of the advantages listed above,
the preparation of gem-diallylated alcohols using tri-
allylaluminum makes this method an attractive alterna-
tive to existing processes.
Compared to other organometallic allylation reagents,
the preparation of triallylaluminum is relatively easy
and the operation procedures are quite simple and con-
venient. For example, the preparation of allylsamarium
reagents from samarium metal and allyl bromide is more
expensive and reactions of allylsamarium are limited to
acid azides, acid chlorides do not react with allylsamar-
ium, 3f and allyltrimethylsilane requires a longer time
(16 h) and lower temperature (À60 ꢁC).12b Similarly,
the preparation of allylzinc is also troublesome, requir-
ing a longer reaction time and the use of allyltin reagents
is environmentally harmful due to its toxic nature.
Spirolactones are important structural units, and
spirobicyclic cores display an important role in the
development of new bioactive substances.2 5,5-Diallyl-
dihydro-furan-2-one 10 and 6,6-diallyl-tetrahydro-pyr-
an-2-one 11 can be easily converted into spirolactones,
which have been reported.11 The preparation of spiro-
lactones uses a sequence involving allylation of cyclic
anhydrides followed by ring closing metathesis (RCM)
(Scheme 3).
Acknowledgements
Financial support provided by the National Science
Council of the Republic of China and National Taiwan
Normal University (96TOP001) is gratefully acknowl-
edged. We also thank Professor Dr. Milton. S. Feather,
for his helpful discussions during the preparation of this
manuscript.
References and notes
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Commun. 2002, 32, 2829; (h) Sormunen, G. J.; Lewis, D.
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Tetrahedron 2002, 58, 5301; (j) Ishino, Y.; Mihara, M.;
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Anjaneyulu, S. Tetrahedron Lett. 2002, 43, 3783.
In conclusion, we report on the development of a simple
and general procedure for the gem-diallylation of deriv-
atives of carboxylic acids using triallylaluminum.13 The
advantages of the reaction are as follows: (1) the reac-
tion is applicable to a wide variety of carboxyl deriva-
tives, (2) the preparation of triallylaluminum is
relatively straightforward, (3) the reaction time is short,
(4) the reaction proceeds at room temperature, (5) the
product yields are high and (6) the reaction proceeds,
even when sterically hindered starting products are em-
n
n
n
RCM
(CH2=CHCH2)3Al
O
O
O
O
O
O
O
spirolactones
10
11
8
n = 0
n = 1
9
Scheme 3.

K.-H. Shen et al. / Tetrahedron Letters 48 (2007) 6348–6351
6351
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1999, 99, 1387; (c) Gung, B. W. Chem. Rev. 1999, 99, 1377.
13. General procedures for diallylation of derivatives of car-
boxylic acid: A typical experimental procedure is described
for the gem-diallylation of benzoyl chloride 2a with
triallylaluminum 1. To a stirred solution of benzoyl
chloride 2a (1.0 mmol) in ether (3 mL), the triallylalumi-
num reagent 1 (1.2 mmol, 0.6 M · 2 mL) was added
rapidly at 20 ꢁC under nitrogen. After 30 min., the mixture
was quenched by adding ice cold dilute HCl(aq) at 0 ꢁC.
The reaction mixture was extracted with Et2O (3 · 25 mL)
and the combined ether layers were dried over anhydrous
MgSO4. The mixture was filtered and then the solvent was
evaporated under reduced pressure to give a quantitative
yield of 3a. The crude product was passed through a small
plug of silica to give pure 3a as colorless oil in 98% yield.
All spectral data are consistent with those reported in the
literature. A similar procedure was followed for the
gem-diallylation of carboxylic esters, anhydrides, and
acyl azides. 4-Adamantan-1-yl-hepta-1,6-dien-4-ol (3f):
1H NMR (400 MHz, CDCl3): d 1.60–1.69 (m, 12H), 1.73
(br s 1H), 1.95–1.99 (m, 3H), 2.29 (dd, 2H, J = 14.2,
6.4 Hz), 2.37 (dd, 2H, J = 14.2, 6.4 Hz), 5.05–5.09 (m,
4H), 5.86–5.96 (m, 2H); 13C NMR (100 MHz, CDCl3): d
28.6, 36.3, 37.0, 39.0, 40.0, 75.9, 117.7, 135.5; GC/MS: m/z
246 (M+); HRMS Calcd for C17H26O [M+], 246.1984;
found, 246.1981.
8. Triallylaluminum 1 was prepared according to the proce-
dures described in Ref. 10.
9. The concentration of triallylaluminum 1 was determined
by the following methods: (a) Gilman, H.; Haubein, A. H.
J. Am. Chem. Soc. 1944, 66, 1515; (b) Bergbreiter, D. E.;
Pendergrass, E. J. Org. Chem. 1981, 46, 219; (c) Bowen,
M. E.; Aavula, B. R.; Mash, E. A. J. Org. Chem. 2002, 67,
9087.
10. Shen, K.-H.; Yao, C.-F. J. Org. Chem. 2006, 71,
3980.
11. (a) Sabitha, G.; Reddy, C. S.; Babu, R. S.; Yadav, J. S.
Synlett 2001, 1787; (b) Michaut, M.; Santelli, M.; Parrain,
J.-L. J. Organomet. Chem. 2000, 606, 93; (c) Michaut, M.;
Santeli, M.; Parrain, J.-L. Tetrahedron Lett. 2003, 44,
2157.