Indium(III) chloride catalyzed allylation of gem-diacetates: A facile synthesis of homoallyl acetates

Article abstract of DOI:10.1246/cl.2001.18

Indium(III) chloride is found to catalyze efficiently the allylation of gem-diacetates with allyltrimethylsilane at room temperature to afford the corresponding homoallylic acetates in high yields with good regioselectivity.

Full text of DOI:10.1246/cl.2001.18

18
Chemistry Letters 2001
Indium(III) Chloride Catalyzed Allylation of gem-Diacetates:
A Facile Synthesis of Homoallyl Acetates
J. S. Yadav,* B.V. Subba Reddy, Ch. Madhuri, and G. Sabitha
Organic Division I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
(Received October 5, 2000; CL-000906)
the corresponding homoallylic acetates in high yields.7 The
reactions proceeded smoothly at ambient temperature and com-
pleted within 5–10 h of reaction time. The results as summa-
rized in Table 1 clearly reveal the scope and generality of the
reaction with respect to various diacetates. The reactions
underwent quite cleanly without any side reactions and the
mono-allylated products were obtained in 70–90% yield.
However, in the case of acylals derived from electron rich alde-
hydes, bis-allylated products were isolated in 10–15% along
with desired homoallylic acetates. This is because of the low
nucleophilicity of allylsilanes and low electrophilicity of elec-
tron rich aldehydes which requires strong Lewis acids for acti-
vation. Strong Lewis acids promoted carbocation formation
becomes increasingly facile as the aromatic aldehyde increases
Indium(III) chloride is found to catalyze efficiently the
allylation of gem-diacetates with allyltrimethylsilane at room
temperature to afford the corresponding homoallylic acetates in
high yields with good regioselectivity.
Lewis acid promoted carbon–carbon bond forming reac-
tions are of great interest because of their unique reactivity and
selectivity. Among various Lewis acid catalyzed C–C bond
forming reactions, the allylation of carbonyl compounds or their
equivalents with allylsilanes is one of the most useful synthetic
reactions1 in organic synthesis. gem-Diacetates are ambident
substrates containing two types of reactive carbon centers, the
carbon atom of a protected aldehyde function and the carbonyl
group in the ester moieties. In general, carbon nucleophiles
will predominantly attack the former center and displace one of
the acyloxy groups affording substitution products in good
yields.2,3 Even though, gem-diacetates are readily available
from the corresponding aldehydes, these compounds have
received little attention as substrates4 for nucleophilic substitu-
tion reactions. Generally, the homoallylic acetates are prepared
from the addition of allylsilane to aldehydes followed by in situ
acylation with acetic anhydride5 but these procedures involve
longer reaction times and produce a mixture of products con-
taining the homoallylic alcohol, diacetate and double-allylated
product along with desired homoallylic acetates. Further, most
of these Lewis acids are moisture sensitive and they decompose
or deactivate under quenching conditions.
Recently, indium(III) halides have received special atten-
tion as mild Lewis acids in various tranformations6 such as
Mukaiyama aldol reactions, Diels–Alder reactions, Mannich
reactions, Prins-type cyclizations, and Michael reactions in both
aqueous and non-aqueous media. Unlike, traditional Lewis
acids such as TiCl4, SnCl4, BF3·OEt2 and AlCl3, indium(III)
chloride is stable and reusable in water. These unique proper-
ties inherent to InCl3 prompted us to explore this catalyst for
the mono substitution of gem-diacetates with allyltrimethylsi-
lane.
In this communication, we wish to report a mild and highly
efficient procedure for the allylation of gem-diacetates (acylal)
with allyltrimethylsilane using indium(III) chloride as the cata-
lyst (Scheme 1). The reaction of benzylidene 1,1-diacetate with
allyltrimethylsilane in the presence of 10% indium(III) chloride
gave the homoallylic acetate in 90% yield. Similarly, several
aldehyde acylals were reacted with allyltrimethylsilane to give
Copyright © 2001 The Chemical Society of Japan

Chemistry Letters 2001
19
in electron density that results in di-allylation. Further, the
reaction of aldehydes with allyltrimethylsilane and acetic anhy-
dride in the presence of 15% indium(III) chloride in
dichloromethane led directly to homo-allylic acetates in high
yields.7b Both activated and unactivated aldehyde acylals were
converted into the corresponding homoallylic acetates in
70–90% yield. However, in the case of aliphatic aldehyde acy-
lals, moderate yields of products were obtained after a long
reaction time (8–10 h) due to their intrinsic lower reactivity.
The ketone acylals did not work under the present reaction con-
ditions. Among various solvents such as CH3NO2, CH2Cl2,
CH3CN, and H2O used for this transformation, CH3NO2 and
CH2Cl2 are found to be effective interms of conversion and
reaction time. Although this reaction proceeds smoothly in
commercial grade dichloromethane, the reaction was unsuc-
cessful in water. Further, we have examined the catalytic activ-
ity of various Lewis acids such as InCl3, YbCl3, BF3·OEt2,
TaCl5, and YCl3 in the allylation reaction. Among these cata-
lysts, InCl3 is found to be the most effective.
In conclusion, we have developed a new and efficient pro-
cedure for the allylation of gem-diacetates with allyltrimethylsi-
lane using indium(III) chloride. The method offers several
advantages like mild reaction conditions, greater selectivity,
high yields of products, regeneration of the catalyst, and simple
experimental/product isolation procedures which makes it a
useful and attractive process for the preparation of homoallyl
acetates.
b) B. M. Trost, C. B. Lee, and J. M. Weiss, J. Am. Chem.
Soc., 117, 7247 (1995).
4
a) M. Sandberg and L. K. Sydnes, Tetrahedron Lett., 39,
6361 (1998). b) F. R. Heerden, J. J. Huyser, D. B. G.
williams, and C. W. Holzapfer, Tetrahedron Lett., 39, 5281
(1998). c) J. S. Yadav, B. V. Subba Reddy, and G. S. Kiran
Kumar Reddy, Tetrahedron Lett., 41, 2695 (2000).
5
6
a) V. K. Aggarwal and G. P. Vennall, Synthesis, 1998,
1822, and references cited therein.
a) T. P. Loh, J. Pei, and M. Lin, Chem. Commun., 1996,
2315. b) T. P. Loh and L. L. Wei, Tetrahedron Lett., 39,
323 (1998). c) G. Babu, and P. T. Perumal, Aldrichimica
Acta., 33, 16 (2000).
7
General Procedure: a) Conversion of gem-diacetate to
homoallylic acetate: a mixture of diacetate (5 mmol)
allyltrimethylsilane (6 mmol) and InCl3 (10% w/w of diac-
etate) in dichloromethane (15 mL) was stirred at room tem-
perature for an appropriate time (Table 1). After comple-
tion of the reaction, as indicated by TLC, the reaction mix-
ture was diluted with water (20 mL) and extracted twice
with dichloromethane (2 × 15 mL). The combined organic
layers were dried over anhydrous Na2SO4, concentrated in
vacuo, and purified by column chromatography on silica
gel (Merck, 100–200 mesh; ethyl acetate–hexane, 1:9) to
afford pure homoallylic acetate.
b) Conversion of aldehyde to homoallylic acetate: A mix-
ture of aldehyde (5 mmol), allyltrimethylsilane (6 mmol),
acetic anhydride (5 mmol) and InCl3 (15% w/w of alde-
hyde) in dichloromethane or nitromethane (15 mL) was
stirred at room temperature for 5–8h. After completion of
the reaction as indicated by TLC, the reaction mixture was
neutralized with aqueous NaHCO3 solution and extracted
twice with dichloromethane (2 × 15mL). The combined
organic layers were dried over anhydrous Na2SO4, concen-
trated in vacuo and purified by column chromatography on
silica gel (Merck, 100–200 mesh; ethyl acetate–hexane,
1:9) to afford pure homoallylic acetates in 75–85% yield.
Representative data for compound 2a: 1H NMR (CDCl3): δ
2.05 (s, 3H), 2.55 (m, 2H), 5.05 (m, 2H), 5.65 (m, 1H),
5.80 (t, 1H, J = 6.8Hz), 7.30 (m, 5H). IR (KBr): ν 3050,
2980, 1740, 1620, 1580, 1230, 970 cm–1.
BVS thanks CSIR, New Delhi for the award of a fellowship.
References and Notes
1
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2
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3
a) B. M. Trost and J. Vercauteren, Tetrahedron Lett., 26,
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