Metal zinc-promoted gem-bisallylation of acid chlorides with allyl chlorides in the presence of chlorotrimethylsilane

Article abstract of DOI:10.1016/S0040-4039(02)01437-5

Treatment of acid chlorides (2) with allyl chlorides (1) in the presence of zinc dust and a catalytic amount of chlorotrimethylsilane (TMSCl) in THF brought about highly facile and effective coupling to give the corresponding gem-bisallylation products, 4-hydroxy-penta-1,6-dienes (3), in good to excellent yields. These reactions are assumed to proceed through allylzinc intermediates generated in situ.

Full text of DOI:10.1016/S0040-4039(02)01437-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 6601–6604
Metal zinc-promoted gem-bisallylation of acid chlorides with
allyl chlorides in the presence of chlorotrimethylsilane
Yoshio Ishino,* Masatoshi Mihara and Manabu Kageyama
Osaka Municipal Technical Research Institute, 1-6-50, Morinomiya, Joto-ku, Osaka 536-8553, Japan
Received 7 June 2002; revised 1 July 2002; accepted 12 July 2002
Abstract—Treatment of acid chlorides (2) with allyl chlorides (1) in the presence of zinc dust and a catalytic amount of
chlorotrimethylsilane (TMSCl) in THF brought about highly facile and effective coupling to give the corresponding gem-bisallyl-
ation products, 4-hydroxy-penta-1,6-dienes (3), in good to excellent yields. These reactions are assumed to proceed through
allylzinc intermediates generated in situ. © 2002 Elsevier Science Ltd. All rights reserved.
The reaction of organometallics and carbonyl com-
pounds provides a fundamental methodology in syn-
thetic organic chemistry. Aldehydes, ketones, esters and
acid halides are widely used as convenient starting
materials for such transformations. Allylation and gem-
bisallylation of these are most interesting processes
since these are useful methods for the preparation of
homoallylic alcohols, b,g-unsaturated ketones, and so
on.1 Various metals such as In, Sm, Mg, sonoelectro
produced Zn, Sn, Al, and so on have been used for this
purpose.2 Among these, however, the bisallylation reac-
tions of carboxylic esters and acid chlorides has scarcely
been investigated.3 The synthetic utility of these meth-
ods may be considerably limited because special equip-
ment, expensive reagents, and multi-step procedure are
required. In addition, some of these procedures entail
problems of corrosive and effluent pollution. Therefore,
the development of new allylmetals was explored to
overcome these difficulties. Recently, we have reported
that metallic zinc with chlorotrimethylsilane (TMSCl)
markedly facilitates the olefination of aldehydes and
ketones by reaction with gem-dihalides.4
In this letter, we report a mild, efficient, and convenient
zinc metal-promoted gem-bisallylation reaction of acid
chlorides (1) with allyl chlorides (2) in the presence of
TMSCl to provide various 4-hydroxy-penta-1,6-dienes
(3) in THF (Scheme 1). To our knowledge, gem-bisallyl-
ation of acid chlorides with allyl chlorides using zinc
metal without any pre-treatment has not yet been
reported.5 The present method using these easily avail-
able reagents is also characterized by high operational
simplicity, convenient one-pot, and inexpensive
method. The 4-hydroxy-penta-1, 6-dienes can be easily
converted to many important building blocks for natu-
ral and bioactive product synthesis.6
R3
R2 R3
R2
R3
R4
R5
R5
Cl
Zn/TMSCl
THF
R5
R1
R1
R1
X
+
R2
HO
R5
HO
R2
R4
+
R4
R4
R4
R3
R5
3(γ)
R2
2a R2=R3=R4=R5=H
1a R1=Ph, X=COCl
1b R1=2-Furyl, X=COCl
1c R1=PhCH=CH, X=COCl 1i R1=Ph, X=COOEt
1d R1=MeCH=CH, X=COCl 1j R1=Ph, X=COOCOPh
1e R1=Me, X=COCl
1f R1=Et, X=COCl
1g R1=n-Pr, X=COCl
1h R1=t-Bu, X=COCl
R3
2b R3=R4=R5=H, R2=Me
2c R2=R3=R5=H, R4=Me
2d R2=R3=R4=H, R5=Me
2e R4=R5=H, R2=R3=Me
2f R3=R4=R5=H, R2=Ph
3(α)
1k R1=Ph, X=CN
Scheme 1.
* Corresponding author. Tel.: +81-6-6963-8057; fax: +81-6-6963-8049; e-mail: ishino@omtri.city.osaka.jp
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01437-5

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Y. Ishino et al. / Tetrahedron Letters 43 (2002) 6601–6604
reaction of 1a with crotyl chloride (cis:trans=1:6.2, 2b)
and 3-chloro-1-betene (2d) gave 3b and 3d in 84 and
71% yield, respectively, as a mixture of Z and E isomers
of a and g products. The reaction of 1a with prenyl
chloride (2e) gave selectively a 1:1 monoallylation
product, phenyl prenyl ketone (4e), as a g product. In
the case of cinnamyl chloride (2f), the desired product
3f was obtained in 60% yield as a mixture of a and g
products (a:g=4:1), but the product resulting from the
a attack predominates. For a large number of acid
chlorides, e.g. aryl, alkyl, a,b-unsaturated, and hetero-
aromatic acid chlorides, the reaction with allyl chloride
(2a) did not show any significant effect on the product
yields.
The reactions were usually carried out at 60°C for 4 h
in anhydrous THF containing powdered metallic zinc
(60 mmol), a catalytic amount of TMSCl (3 mmol),
acid chlorides (10 mmol), and allyl chlorides (30
mmol).7 Commercially available zinc dust (purity; 95%)
was used without any pre-treatment. Detailed studies
on the reaction of benzoyl chloride (1a) with allyl
chloride (2a) to 4-phenyl-4-hydroxy-hepta-1,6-diene
(3a) showed that this catalytic cross-coupling is consid-
erably influenced by the molar ratio of 2/1, Zn/1, and
the solvents used, as shown in Table 1.
Noteworthy is the fact that none of the products 3a was
obtained when the reaction was run in the ratio of
2a/1a=1 (entry 1), while increasing the ratio let the
bisallylation reaction proceed smoothly to give 3a in
excellent yields. Though 4-hydroxy-penta-1,6-diene (3a)
was obtained in the absence of TMSCl, the reaction
proceeded more smoothly and efficiently by the addi-
tion of TMSCl. Allyl chloride showed the same satis-
factory reactivity compared with allyl bromide. As
shown in Table 1, the best result for formation of
product 3a was obtained when the relative proportion
of 1a:2a:Zn:TMSCl was 1:2:6:0.3. Also, THF was
found to be a much better solvent for this reaction than
other aprotic solvents such as DMF and DCE.
Table 2. Reaction of benzoylchloride (1a) and allyl chlo-
rides (2) in the presence of Zn/TMSCl
Yield(%)a
Entry
2
Products
1
2
(2a)
(2b)
3a
92
84
Cl
3bb
Cl
3
4
3c
Cl
Cl
97
71
(2c)
(2d)
A combination of zinc metal and a catalytic amount of
TMSCl has been found to promote the transformation
of various acid chlorides with allyl chlorides to the
corresponding cross-coupling gem-bisallylation prod-
ucts under mild reaction conditions. To demonstrate
the efficiency and scope of the present method, we
applied this catalytic system to a variety of allyl chlo-
rides. For the allyl chlorides as coupling partners, the
presence of various alkyl and aryl substituents at the a,
b, and g positions did not exhibit any significant effect
on the yield. The results are summarized in Tables 2
and 3.
3db
4ec
5
6
(2e)
(2f)
86
60
Cl
3fb
Cl
Ph
a; Isolated yield.
b; Stereoisomeric mixture of α- and γ-addition and E- and Z-isomers.
c;
Under the optimized conditions, 1a was treated with
allyl chloride (2a) and methallyl chloride (2c) to pro-
duce 3a and 3c in 92 and 97% yield, respectively. The
Ph
4e
O
Table 1. Zinc-promoted reaction of benzoylchloride (1a) and allylchloride (2a) in the presence of TMSCla
Molar ratio of
Entry
Solvent
2a/1a
Zn/1a
TMSCl/1a
Yield of 3a (%)b
1
2
3
4
5
6
7
8
THF
THF
THF
THF
THF
THF
DMF
DCEe
1
2
3
3
3
3
3
3
6
6
6
6
3
6
6
6
0.3
0.3
0.3
0.3
0.3
0
0c
85
92
91d
63
80
63
0
0.3
0.3
a General reaction conditions: 1a 10 mmol was used in THF 40 ml at 60°C for 4 h.
b Isolated yield.
c Adducts of THF and 1a, such as 4-chlorobutylbenzoates, were obtained in 28% yield.
d Allyl bromide was used instead of allyl chloride.
e 1,2-Dichloroethane

Y. Ishino et al. / Tetrahedron Letters 43 (2002) 6601–6604
6603
Table 3. Reaction of allyl chlorides (2a) with various
acylating agents in the presence of Zn/TMSCl
In conclusion, we have demonstrated that in situ gener-
ated allylzinc reagents from the reaction of zinc with
allyl chlorides in the presence of TMSCl could be
effectively cross-coupled with acid chlorides to give the
corresponding gem-bisallylation products, 4-hydroxy-
penta-1,6-dienes (3), in good to excellent yields. The
present method complements the existing synthetic
method due to some advantageous properties of the
allylzinc reagents such as availability and selectivity,
operational simplicity, and low toxicity.
Yield(%)a
Entry
RCOX
Products 3
Ph
HO
Furyl
O
(3a)
(1a)
92
1
Ph
O
Cl
Cl
(1b)
(1c)
(1d)
(3b)
(3c)
(3d)
43
43
2
3
HO
O
O
Ph
References
Ph
Cl
HO
HO
1. For example: Yamamoto, Y.; Asao, N. Chem. Rev. 1993,
93, 2207; Ranu, B. C.; Majee, A.; Das, A. R. Tetrahedron
Lett. 1995, 36, 4885; Hamann-Gaudinet, B.; Namy, J.-L.;
Kagan, H. B. Tetrahedron Lett. 1997, 38, 6585.
O
4
66
66
66
Cl
2. For example: Durant, A.; Delplancke, J. L.; Libert, V.,
Reisse, J. Eur. J. Org. Chem. 1999, 2845; Machrouhi, F.;
Parlea, E.; Namy, J.-L. Eur. J. Org. Chem. 1998, 2431;
Bubnov, Y. N.; Misharin, M. A.; Ingnatenko, A. V.
Tetrahedron Lett. 1997, 38, 6259; Snowden, R. L.; Muller,
B. L.; Schulte-Elte, K. H. Tetrahedron Lett. 1982, 23, 335;
Tanaka, H.; Nakahata, S.; Watanabe, H.; Zhao, J.; Kuro-
boshi, M.; Torii, S. Inorg. Chim. Acta 1999, 296, 204.
3. (a) Cardillo, G.; Simone, A. D.; Mingardi, A.; Tomasini,
C. Synlett 1995, 1131; (b) Yadav, J. S.; Srinivaa, D.;
Reddy, G. S.; Bindu, K. H. Tetrahedron Lett. 1997, 38,
8745; (c) Inoue, K.; Shimizu, Y.; Shibata, I.; Baba, A.
Synlett 2001, 1659.
O
(3e)
(3f)
5
(1e)
HO
HO
Cl
O
6
7
8
(1f)
Cl
O
(1g)
(3g)
(3h)
66
77
HO
Cl
O
t-Bu
HO
(1h)
Cl
4. Ishino, Y.; Mihara, M.; Nishihama, S.; Nishiguchi, I. Bull.
Chem. Soc. Jpn. 1998, 71, 2669.
(5)
(6)
(7)
9
3a
3a
3a
88
38
43
PhCOOEt
5. A reaction of allylbromide with acid chlorides and Zn
under sonication was reported to provide b,g-unsaturated
ketones: Ranu, B. C.; Majee, A.; Das, A. R. Tetrahedron
Lett. 1996, 37, 1109.
10
11
(PhCO)2O
PhCN
6. Sabitha, G.; Reddy, Ch. S.; Babu, R. S.; Yadav, J. S.
Synlett 2001, 1787.
a; Isolated yield.
7. General procedure for the Zn-promoted cross-coupling of
acyl chlorides with allyl chlorides in the presence of
TMSCl: A dry THF suspension (10 mL) of Zn metal (60
mmol, 3.94 g) and TMSCl (3 mmol, 0.33 g) was stirred
under a nitrogen atmosphere for about 15 min at 50°C.A
mixture of benzoyl chloride (10 mmol, 1.40 g) and allyl
chloride (30 mmol, 2.28 g) in 10 mL of THF was slowly
added to the suspended solution, and the reaction mixture
was then stirred for about 3 h at the same temperature.
The reaction mixture was then poured into 200 mL of
saturated aqueous ammonium chloride solution and the
crude reaction products were extracted using three 100 mL
portions of ether. The combined ethereal solution was
washed with a 100 mL portion of water, and then dried
over anhydrous magnesium sulfate. After removing the
drying agent by filtration, the solvent was evaporated by
distillation. Then, the products were isolated by silica-gel
column chromatography of the resulting residue. All new
compounds, 3 and 4 prepared in this study, were identified
Further applications of the reaction were studied by
using esters (5), acid anhydrides (6), and nitriles (7)
instead of acid chlorides. The reaction of 5, 6, and 7
with allyl chloride lies to the formation of 3a in the
yield of 88, 38, and 43%, respectively. These results well
demonstrated that the allylzinc reagent generated from
the reaction of zinc with allyl chloride in the presence of
a catalytic amount of TMSCl has sufficient reactivity
for some of the unreactive carbonyl and nitrile
compounds.
Although the mechanistic details still remain ambigu-
ous, the reaction may proceed through in situ generated
allylzinc as a reaction intermediate. This in situ gener-
ated allylzinc gave the 1:1 products (allylic ketones) by
the reaction with acid chlorides, and then the 1:1 prod-
ucts react with additional allylzinc smoothly to obtain
the 1:2 cross-coupling products 3.8,9 Elucidation of the
detailed reaction mechanism must await further study.
1
by H and 13C NMR, IR and mass spectroscopes. Typical
spectra data is as follows: 4-hydroxy-4-phenyl-hepta-1,6-
diene (3a) 1H NMR (300 MHz, CDCl3) l 7.26 (m, 5H),
5.53 (m, 2H), 5.06 (d, J=24.4 0 Hz, 2H), 5.05 (s, 1H), 2.53
(q/d, J=13.58/6.06 Hz, 4H), 2.17 (s. 1H); 13C NMR (75

6604
Y. Ishino et al. / Tetrahedron Letters 43 (2002) 6601–6604
MHz, CDCl3) l 135.97, 133.69, 124.07, 118.68, 73.22, 45.39,
30.90; IR (film) 3552, 3075, 2978, 1639, 1446, 999, 702 cm−1
8. (a) Knochel, P. In Active Metals; Fu¨rstner, A., Ed.; VCH:
Weinheim, New York, Basel, Cambridge, Tokyo, 1995; p.
191; (b) Fu¨rstner, A. Angew. Chem., Int. Ed. Engl. 1993, 32,
164; (c) Takai, K.; Kakiuchi, T.; Kataoka, Y.; Utimoto, K.
J. Org. Chem. 1994, 59, 2671; (d) Stadtmu¨ller, H.; Greve,
B.; Lennick, K.; Chair, A.; Knochel, P. Synthesis 1995, 69;
(e) Picotin, G.; Miginiac, P. J. Org. Chem. 1987, 52, 4796.
9. Inthisreaction, therolesofTMSClmaybepostulatedmainly
in two ways, that is, one is activation of zinc metal surface
and the other one is activation of 1 and 2 by coordination
of the Si atom to the carbonyl group and the chlorine atom.
;
HRMS(EI)calcdforC10H16OM+ 188.1201, found188.1197.
4-Hydroxy-4-(2-propenyl)-hepta-1,6-diene (3j) 1H NMR
(300 MHz, CDCl3) l 5.65 (m, 2H), 5.14 (s, 2H), 5.10 (d,
J=10.46 Hz, 2H), 2.29 (s, 2H), 2.29 (d. J=10.03 Hz, 4H),
2.17 (s, 1H), 1.72 (d, J=6.24 Hz, 2H), 1.27 (s, 2H), 0.87 (m,
1H); 13C NMR (75 MHz, CDCl3) l 135.97, 133.69, 124.07,
118.68, 73.22, 45.39, 30.90; IR (film) 3465, 2934, 2921, 1438,
1420, 1363, 1223, 998, 972, 915 cm−1; HRMS (EI) calcd for
C13H16O M+ 152.1201, found 152.1205.