Indium mediated allylation and propargylation reactions of dimethyl acetals and ketals

Article abstract of DOI:10.1016/S0040-4039(01)00042-9

Indium mediated allylation and propargylation reactions of acetals and ketals with various allyl or propargyl bromides in aqueous media successfully provided the corresponding homoallylic or homopropargylic (and allenylic) alcohol, respectively, in moderate to good yields. Highly chemoselective allylation is also described. The ketal and aryl acetal could be selectively allylated over the aliphatic one in 80-84% yields.

Full text of DOI:10.1016/S0040-4039(01)00042-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 1957–1959
Indium mediated allylation and propargylation reactions of
dimethyl acetals and ketals
Jin Sun Kwon, Ae Nim Pae, Kyung Il Choi, Hun Yeong Koh, Youseung Kim and Yong Seo Cho*
Biochemicals Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang,
Seoul 130-650, South Korea
Received 11 December 2000; accepted 10 January 2001
Abstract—Indium mediated allylation and propargylation reactions of acetals and ketals with various allyl or propargyl bromides
in aqueous media successfully provided the corresponding homoallylic or homopropargylic (and allenylic) alcohol, respectively, in
moderate to good yields. Highly chemoselective allylation is also described. The ketal and aryl acetal could be selectively allylated
over the aliphatic one in 80–84% yields. © 2001 Published by Elsevier Science Ltd.
Indium mediated Barbier type reaction of carbonyl
compounds has attracted considerable interest since
Butsugan and Araki first reported the reaction in 1988.1
Early this year, we reported deketalization and
chemoselective deacetalization reactions with allyl bro-
mide in aqueous media.2 As an extension of the
research, we performed the indium mediated allylation
and propargylation reactions of acetals and ketals in
aqueous media. The overall reaction is a one-pot depro-
tection–allylation/propargylation process (Scheme 1).3
dimethyl acetals of 4-methoxybenzaldehyde (2) and
trans-cinnamaldehyde (3), allylation and propargyla-
tion reactions proceeded more efficiently than benzalde-
hyde dimethyl acetal (1).
Allylation and propargylation reactions of cyclohex-
anone dimethyl ketal were also investigated (Table 2).
All reactions were carried out under the same reaction
conditions mentioned above.3 The reaction of 2,3-
dibromopropene (Entry 4) and methyl 4-bromocroto-
nate (Entry 6), which showed low yields with acetals in
Table 1, did not proceed at all. These results imply that
aliphatic ketals are less reactive than aryl as well as
conjugated acetals.
Firstly, the allylation and propargylation reactions of
dimethyl acetals of benzaldehyde (1), 4-methoxyben-
zaldehyde (2) and trans-cinnamaldehyde (3) with nine
bromides were examined (Table 1). With the exception
of propargylic bromides (Entries 8 and 9), every bro-
mide seemed to have reacted in a g-addition manner.
Propargyl bromide gave mixed products resulting from
a- and g-addition, and 1-bromo-2-butyne provided only
the a-addition product. Compared with benzaldehyde
itself, benzaldehyde dimethyl acetal (1) required a
longer reaction time, and gave the corresponding
product in somewhat lower yields. In the cases of
From our previous work,2 we knew that ketals and
aromatic acetals can be selectively deprotected in the
presence of aliphatic acetals by the action of allyl
bromide in aqueous media. Based on this information,
we carried out a chemoselective allylation reaction.
Scheme 2 illustrates the chemoselective allylation of
[4-(2,2-dimethoxyethyl)phenyl]dimethoxymethane
and 1,1,5,5-tetramethoxy hexane (6). The diacetal of
(4)
In/allylic or
propargylic bromide
R"
O
CH3O
R'
OCH3
R
HO
R'
R
aq. THF
R'
R
R' = H, alkyl or aryl
(acetal or ketal)
R" = allyl, propargyl, allenyl
Scheme 1.
* Corresponding author. Fax: +82-2-958-5189; e-mail: ys4049@kist.re.kr
0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)00042-9

1958
J. S. Kwon et al. / Tetrahedron Letters 42 (2001) 1957–1959
aromatic aldehyde 4 and aliphatic acetal ketal 6 reacted
preferentially with aromatic acetal and ketal under the
same reaction conditions to provide the selective allyla-
good yields while keeping the aliphatic acetal intact.
This method will provide a useful tool for allylation
and propargylation of acetals and ketals without depro-
tection steps in aqueous media.
tion products
respectively.
5 and 7 in 84 and 80% yields,
In conclusion, indium mediated allylation and propar-
gylation reactions of acetals and ketals successfully
provided the corresponding alcohol in the presence of
various allyl or propargyl bromides in aqueous THF in
moderate to good yields, except in a few cases. Further-
more, chemoselective allylations were accomplished in
Acknowledgements
The authors are grateful to the Korea Ministry of
Science and Technology for financial support.
Table 1. Indium mediated allylation and propargylation of acetals of conjugated aldehydesa
a All reactions were carried out on a 0.2–0.4 mmol scale at rt. b Results for benzaldehyde. c Diastereomeric ratio was determined by 1H NMR.
d,e Propargyl:allenyl=1:2. f Propargyl:allenyl.

J. S. Kwon et al. / Tetrahedron Letters 42 (2001) 1957–1959
1959
Table 2. Indium mediated allylation and propargylation of cyclohexanone dimethyl ketala
OH
OCH3
OCH3
Br
OCH3
OCH3
84%
80%
In, aq. THF, 6h, rt
CH3O
CH3O
4
5
7
Br
CH3O OCH3
OH
OCH3
OCH3
OCH3
OCH3
In, aq. THF, 5h, rt
6
Scheme 2.
References
Y.; Kim, Y.; Cho, Y. S. Bull. Korean Chem. Soc. 2000, 21,
453.
1. (a) Araki, S.; Ito, H.; Butsugan, Y. J. Org. Chem. 1988, 53,
1831–1833; (b) Li, C. J.; Chan, T. H. Tetrahedron Lett.
1991, 32, 7017; (c) Chan, T. H.; Li, C. J.; Lee, M. C.; Wei,
Z. Y. Can. J. Chem. 1994, 72, 1181; (d) Paquette, L.
A.; Bennett, G. D.; Isaac, M. B.; Chhatriwalla, A. J.
Org. Chem. 1998, 63, 1836; (e) Cho, Y. S.; Lee, J. E.; Pae,
A. N.; Choi, K. I.; Koh, H. Y. Tetrahedron Lett. 1999, 40,
1725.
3. Typical reaction procedure is as follows: An acetal or ketal
(0.33 mmol) was dissolved in aqueous THF (H2O/THF=
3/1, v/v) followed by the addition of allyl or propargyl
bromide (0.66 mmol) and indium metal (0.39 mmol) at rt.
After an appropriate reaction time (see Tables 1 and 2), the
reaction mixture was filtered through Celite and washed
with ethyl acetate. The filtrate was treated following a usual
aqueous work-up procedure and purified by column chro-
matography on silica gel to furnish the final products.
2. Kwon, J. S.; Lee, J. G.; Pae, A. N.; Choi, K. I.; Koh, H.
.