Indium triiodide catalyzed direct hydroallylation of esters

Article abstract of DOI:10.1002/ejoc.201000475

The InI₃-catalyzed hydroallylation of esters by using hydroand allysilanes under mild conditions has been accomplished. Many significant groups such as alkenyl, alkynyl, cyano, and nitro ones survive under these conditions. This reaction system, provided routes to both homoallylic alcohols and ethers, in which either elimination of the alkoxy moiety or of the carbonyl oxygen atom could be freely selected by changing the substituents on the alkoxy moiety and on the hydrosilane. In addition, the hydroallylation of lactones took place without ring cleavage to produce the desired cyclic ethers in high yields.

Full text of DOI:10.1002/ejoc.201000475

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201000475
Indium Triiodide Catalyzed Direct Hydroallylation of Esters
Yoshihiro Nishimoto,[a] Yoshihiro Inamoto,[a] Takahiro Saito,[a] Makoto Yasuda,[a] and
Akio Baba*[a]
Keywords: Indium / Esters / Allylation / Hydrosilane / Allylsilanes
The InI3-catalyzed hydroallylation of esters by using hydro-
moiety or of the carbonyl oxygen atom could be freely se-
and allysilanes under mild conditions has been ac- lected by changing the substituents on the alkoxy moiety and
complished. Many significant groups such as alkenyl, alk-
ynyl, cyano, and nitro ones survive under these conditions.
This reaction system provided routes to both homoallylic
alcohols and ethers, in which either elimination of the alkoxy
on the hydrosilane. In addition, the hydroallylation of lac-
tones took place without ring cleavage to produce the de-
sired cyclic ethers in high yields.
Introduction
Esters have the valuable quality of simultaneous accept-
For many years the addition of an organometallic com- ance of two different kinds of nucleophiles. In order to uti-
pound to a carbonyl group has been one of the most impor- lize this property, an aluminum acetal generated by the hy-
tant reactions in alcohol synthesis.[1] Many elegant reac- droalumination of esters with DIBAL has attracted much
tions have been applied to aldehydes and ketones, whereas attention, because it can react with various organometallics
esters have seldom been employed in selective carbon–car- to furnish the desired secondary alcohols (Scheme 1).[2]
bon bond formation due to a low electrophlicity. Strong Therefore, the combination of DIBAL and nucleophiles is
nucleophiles such as Grignard reagents or organolithium an attractive protocol for the direct transformation of es-
compounds are generally required for addition to esters, ters, but the high reducing properties of DIBAL consider-
often causing undesired side reactions. However, because ably limit the chemoselectivity, and most cases require
esters have several advantages over other carbonyl rea- strong nucleophiles like Grignard reagents or equivalent
gents – availability, preservation, and variety –, a sophisti- amounts of a Lewis acid.[3] In addition, it is difficult to
cated application of them would have a significant value in produce ethers by selectively removing the carbonyl oxygen
organic synthesis.
atom of esters.[4] Instead of hydroalumination, hydro-
Scheme 1. Addition of hydride and nucleophile to ester.
silylation of esters produces the corresponding silyl acetals
that should react with nucleophiles. The transition metal
catalyzed hydrosilylation of esters has been achieved, but
no example yet exists for a carbon–carbon bond formation
by direct use of the resulting silyl acetals.[5] We herein report
the direct hydroallylation of esters by using hydro- and al-
lylsilanes. A catalytic amount of InI3 accelerated this hy-
[a] Department of Applied Chemistry, Center for Atomic and
Molecular Technologies (CAMT), Graduate School of
Engineering, Osaka University,
2-1 Yamada-oka, Suita, 565-0871 Osaka, Japan
Fax: +81-6-6879-7387
E-mail: baba@chem.eng.osaka-u.ac.jp
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000475.
3382
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 3382–3386

Indium Triiodide Catalyzed Direct Hydroallylation of Esters
droallylation under mild conditions, and significant func- generated by the removal of the carbonyl oxygen atom of
tional groups such as alkenyl, alkynyl, cyano, and nitro ester 2a (Table 1, Entry 11). HSiMe2Ph, however, did not
ones survive under these conditions. Stepwise treatments of undergo such a change and furnished a high yield of
hydro- and allylsilane are not required. Notably, either eli- alcohol 5a (Table 1, Entry 12). Eventually, isopropyl ester
mination of the alkoxy moiety or the carbonyl oxygen atom 3a produced a higher yield of the ether product 7 (Table 1,
could be freely selected by changing the substituents on the Entries 13 and 14). These results apparently indicate that
alkoxy moiety and on the hydrosilane. To the best of our the determination of the product depends on the differences
knowledge, this is the first practical method for the selective in the bulkiness of the alkoxy moiety of the ester and of the
synthesis of alcohols or ethers by the addition of hydride substitutions on the hydrosilane.
and nucleophiles to esters.
We investigated the scope of applicable esters by using a
combination of methyl esters 1 and HSiMe2Ph, which pref-
erentially forms an alcohol 5 (Table 2). High yields of
homoallyl alcohols 5 were obtained from simple aliphatic
esters such as 1b and 1c with the exception of the bulky 1d
(Table 2, Entries 1–3). The reaction with methyl benzoate
(1e) resulted in a moderate yield even in the presence of
20 mol-% InI3, because aromatic esters generally have a
lower electrophilicity than aliphatic ones (Table 2, Entry 4).
Many kinds of functional groups – methoxy, chloro, nitro,
cyano, alkenyl, alkynyl, and hydroxy – that could not sur-
vive in the previous DIBAL method, were able to tolerate
the conditions used in the present study (Table 2, Entries 5–
11).[3] It is noteworthy that α-halo esters were also appli-
cable, as they are good alternatives to the corresponding
unstable aldehydes (Table 2, Entries 12–15). Substituted all-
ylsilanes 4b and 4c also furnished the corresponding
alcohols 5q and 5r, respectively, in satisfying yields in which
the allylations selectively took place in a γ-addition manner
(Table 2, Entries 16 and 17).
Results and Discussion
In order to find the optimal conditions, ester 1a as a
model substrate was treated with allytrimethylsilane (4a)
and various hydrosilanes in the presence of indium catalysts
(Table 1).[6] InCl3 promoted no reaction, but InBr3 and InI3
gave the desired hydroallylation product 5a in 49% and
73% yields, respectively, along with reduction product 6a
(Table 1, Entries 1–3). It is interesting that the use of a
stronger Lewis acid, In(OTf)3, resulted in recovery of the
starting ester 1a (Table 1, Entry 4). Also, typical and strong
Lewis acids such as BF3·OEt2, AlCl3, and TiCl4 were not
effective.[7] HSiEt3 and phenylsilanes, with the exception of
HSiPh3, had a good effect (Table 1, Entries 3 and 5–7). The
amount of by-product 6a was reduced by the slow addition
of hydrosilanes. Finally, the slow addition of HSiMe2Ph to
a mixture of 1a, 4a, and InI3 was selected as the optimal
conditions and resulted in a 96% yield of 5a (Table 1, En-
try 9). Interestingly, in the reaction with HSiEt3, the use of
Next, in order to produce homoallylic ethers 7, the com-
ethyl ester 2a instead of methyl ester 1a caused a change in bination of a bulky ester and a small hydrosilane, isopropyl
the allylation product from alcohol 5a to ether 7, which was ester 3 and HSiEt3, was employed. A variety of esters gave
Table 1. Optimization of the conditions for the hydroallylation of esters.[a]
Entry
Ester
HSi
InX3
Yields [%][d]
6a
5a
7
8
1[b]
2
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
2a
2a
3a
3a
HSiEt3
HSiEt3
HSiEt3
InCl3
InBr3
InI3
In(OTf)3
InI3
InI3
InI3
InI3
InI3
InI3
InI3
0
49
73
0
71
85
5
93
96
90
7
59
3
0
17
25
0
29
15
3
5
4
9
3
0
5
1
0
0
0
0
0
0
0
52
6
58
74
0
2
1
0
0
0
0
0
0
0
29
3
16
4
3
4[b]
5
HSiEt3
HSiMe2Ph
HSiMePh2
HSiPh3
6
7[b]
8[c]
9[c]
10[c]
11
12
13
14[c]
HSiEt3
HSiMe2Ph
HSiMePh2
HSiEt3
HSiMe2Ph
HSiEt3
InI3
InI3
InI3
32
trace
trace
HSiEt3
7
[a] Ester (1 mmol), hydrosilane (2 mmol), allyltrimethylsilane (4a) (4 mmol), InX3 (0.05 mmol), CH2Cl2 (1 mL), room temperature, 30 min.
[b] Ͼ90% of 1a was recovered. [c] 2 mmol of allyltrimethylsilane was used. Hydrosilane (2 mmol, 1  of CH2Cl2 solution) was added in
1
90 min, and the mixture was stirred for 10 min. [d] Yields were determined by H NMR analysis.
Eur. J. Org. Chem. 2010, 3382–3386
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3383

Y. Nishimoto, Y. Inamoto, T. Saito, M. Yasuda, A. Baba
SHORT COMMUNICATION
Table 2. Selective synthesis of homoallyl alcohol 5 by using various (Scheme 2). As expected, both lactones were effectively al-
methyl esters 1.[a]
lylated without ring cleavage to produce the desired cyclic
ethers 10 and 12 in 79% and 97% yields, respectively.
Table 3. Selective synthesis of homoallylic ethers 7 by using iso-
propyl esters 3.[a]
[a] To the mixture of 1 (1 mmol), allylsilane (2 mmol), InI3
(0.05 mmol), and CH2Cl2 (1 mL), the hydrosilane (2 mmol, 1  of
CH2Cl2 solution) was slowly added in 90 min, and the mixture was
then stirred for 10 min. [b] Yields were determined by 1H NMR
analysis. Values in parentheses indicate isolated yield in different
batch conditions on different scales. [c] Diastereomer ratio: 70:30.
[d] Diastereomer ratio: 62:38.
Scheme 2. Hydroallylation of lactones. Yields were determined by
1H NMR analysis. Values in parentheses indicate isolated yields in
different batch reactions on different scales.
A putative mechanism is illustrated in Scheme 2. First,
[a] To the mixture of 1 (1 mmol), allylsilane (2 mmol), and InI3
InI3-catalyzed hydrosilylation of an ester takes place to gen-
(0.05 mmol), the hydrosilane (2 mL, 1  of CH2Cl2 solution) was
erate silyl acetal 13.[8] In the successive allylation, there are
added in 90 min, and the mixture was stirred for 10 min. [b] Yields
1
two possible routes: one produces alcohol product 5 and
the other produces ether product 7.[4,9] The determination
of the route mainly depends on the steric hindrance of the
alkoxy and siloxy groups. In the case of the methyl ester 1/
HSiMe2Ph system, InI3 interacts with the small methoxy
were determined by H NMR analysis. Values in parentheses indi-
cate isolated yield in different batch reactions and on different
scales. [c] Diastereomer ratio: 59:41. [d] InI3 (0.2 mmol); hydrosi-
lane (2 mmol, 1  of CH2Cl2 solution) was added in 150 min, and
the mixture was stirred for 30 min. [e] Hydrosilane (2 mmol, 1  of
CH2Cl2 solution) was added in 150 min, and the mixture was
stirred for 30 min. [f] Diastereomer ratio: 58:42. [g] Allylsilane group rather than the large siloxy one, and the nucleophilic
(4 mmol). [h] Diastereomer ratio: 53:47. [i] InBr3 (0.05 mmol).
attack of an allylsilane promotes the elimination of the
methoxy group to give homoallyl alcohol 5 [Scheme 3,
Equation (2)]. By contrast, in the isopropyl ester 3/HSiEt3
the corresponding homoallyl ethers 7 in high yields and in system, the hindered isopropoxy group accelerates the inter-
high selectivities, as shown in Table 3. In addition, we ac- action between InI3 and the siloxy group to provide the
complished the hydroallylation of lactones 9 and 11 ether product 7 [Scheme 3, Equation (3)].
3384
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 3382–3386

Indium Triiodide Catalyzed Direct Hydroallylation of Esters
Scheme 3. Putative mechanism.
vol. 2 (Eds.: R. H. Crabtree, D. M. P. Mingos), Elsevier, Ox-
ford, UK, 2007.
Conclusions
[2]
For references on the use of DIBAL, see: a) J. M. Takacs,
M. A. Helle, F. L. Seely, Tetrahedron Lett. 1986, 27, 1257–1260;
b) S. D. Burke, D. N. Deaton, R. J. Olsen, D. M. Armistead,
B. E. Blough, Tetrahedron Lett. 1987, 28, 3905–3906; c) S.
Kano, Y. Yuasa, T. Yokomatsu, S. Shibuya, Chem. Pharm. Bull.
1989, 37, 2867–2869; d) T. Ibuka, H. Habashita, A. Otaka, N.
Fujii, J. Org. Chem. 1991, 56, 4370–4382; e) S. Kiyooka, M.
Shirouchi, J. Org. Chem. 1992, 57, 2–4; f) R. Polt, M. A. Pe-
terson, L. DeYoung, J. Org. Chem. 1992, 57, 5469–5480; g) S.
Kiyooka, M. Shirouchi, Y. Kaneko, Tetrahedron Lett. 1993, 34,
1491–1494; h) T. Ishihara, H. Hayashi, H. Yamanaka, Tetrahe-
dron Lett. 1993, 34, 5777–5780; i) T. Ishihara, A. Takahashi,
H. Hayashi, H. Yamanaka, T. Kubota, Tetrahedron Lett. 1998,
39, 4691–4694; j) T. H. Hoye, L. C. Kopel, T. D. Ryba, Synthe-
sis 2006, 1572–1574; k) T. Yamazaki, R. Kobayashi, T. Kita-
zume, T. Kubota, J. Org. Chem. 2006, 71, 2499–2502. For refer-
ences on the use of other metal hydrides, see: l) D. L. Comins,
J. J. Herrick, Tetrahedron Lett. 1984, 25, 1321–1324; m) S. Hal-
louis, C. Saluzzo, R. Amouroux, Synth. Commun. 2000, 30,
313–324.
The InI3-catalyzed hydroallylation of an ester by using
hydro- and allylsilanes has been accomplished, providing
routes to both homoallylic alcohols and ethers. The deter-
mination of the route depended on the combination of the
alkoxy moiety of the ester and the substituents of the hydro-
silane. In addition, this reaction system has a high chemo-
selectivity, and various functional groups survived (nitro,
cyano, alkenyl, alkynyl, hydroxy). Further application and
study of the details of this reaction mechanism are ongoing.
Experimental Section
Typical Procedure for the Hydroallylation of 1b (Table 2, Entry 1):
Dimethylphenylsilane (2 mmol, 1  of CH2Cl2 solution) was slowly
(90 min) added to a suspended solution of InI3 (0.05 mmol), 1b
(1 mmol), and allyltrimethylsilane (2 mmol) in dichloromethane
(1 mL) by using a syringe pump at room temperature. The reaction
mixture was stirred for 10 min and then quenched with TBAF
(5 mmol of a 1  THF solution). The resulting mixture was poured
into 1  aq. HCl (10 mL) and extracted with Et2O. The organic
layer was dried with MgSO4, and the solvent was removed under
reduced pressure to afford the crude product, which was analyzed
by NMR spectroscopy.
[3]
For the reaction of functional groups with DIBAL, see: P. Gal-
atsis in Encyclopedia of Reagents for Organic Synthesis (Ed.:
L. A. Paquette), John Wiley & Sons, Chichester, England,
2004.
D. Sames, Y. Liu, L. DeYoung, R. Polt, J. Org. Chem. 1995,
60, 2153–2159.
[4]
[5]
For transition metal catalysed deoxygenative hydrogenation of
esters by hydrosilylation, see: a) S. C. Berk, K. A. Kreutzer,
S. L. Buchwald, J. Am. Chem. Soc. 1991, 113, 5093–5095; b)
S. C. Berk, S. L. Buchwald, J. Org. Chem. 1992, 57, 3751–3753;
c) K. J. Barr, S. C. Berk, S. L. Buchwald, J. Org. Chem. 1994,
59, 4323–4326; d) Z. Mao, B. T. Gregg, A. R. Culter, J. Am.
Chem. Soc. 1995, 117, 10139–10140; e) M. C. Hansen, X. Verd-
aguer, S. L. Buchwald, J. Org. Chem. 1998, 63, 2360–2361; f)
T. Ohta, M. Kamiya, K. Kusui, T. Michibata, M. Nobutomo,
I. Furukawa, Tetrahedron Lett. 1999, 40, 6963–6966; g) M. Iga-
rashi, R. Mizuno, T. Fuchikami, Tetrahedron Lett. 2001, 42,
2149–2151; h) M. Yato, K. Homma, A. Ishida, Tetrahedron
Lett. 2001, 42, 5353–5359; i) K. Matsubara, T. Iura, T. Maki,
H. Nagashima, J. Org. Chem. 2002, 67, 4985–4988.
For our studies on indium-catalyzed reaction systems by using
silyl nucleophiles, see: a) T. Miyai, Y. Onishi, A. Baba, Tetrahe-
dron Lett. 1998, 39, 6291–6294; b) T. Miyai, M. Ueba, A. Baba,
Synlett 1999, 182–184; c) T. Miyai, Y. Onishi, A. Baba, Tetrahe-
dron 1999, 55, 1017–1026; d) M. Yasuda, Y. Onishi, T. Ito, A.
Baba, Tetrahedron Lett. 2000, 41, 2425–2428; e) M. Yasuda, Y.
Supporting Information (see footnote on the first page of this arti-
cle): General information and procedures, characterization data of
the prepared compounds.
Acknowledgments
This work was supported by the Ministry of Education, Culture,
Sports, Science and Technology, Japan through Grant-in-Aids for
Scientific Research on Priority Areas [No. 18065015 (“Chemistry
of Concerto Catalysis”) and No. 20036036 (“Synergistic Effects for
Creation of Functional Molecules”)] and for Scientific Research
(No. 21350074).
[6]
[1] a) C. H. Heathcock in Comprehensive Organic Synthesis, vol. 2
(Eds.: B. M. Trost, I. Fleming), Pergamon, Oxford, UK, 1991;
b) P. Knochel in Comprehensive Organometallic Chemistry III,
Eur. J. Org. Chem. 2010, 3382–3386
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3385

Y. Nishimoto, Y. Inamoto, T. Saito, M. Yasuda, A. Baba
SHORT COMMUNICATION
Onishi, M. Ueba, T. Miyai, A. Baba, J. Org. Chem. 2001, 66,
7741–7744; f) Y. Onishi, D. Ogawa, M. Yasuda, A. Baba, J.
Am. Chem. Soc. 2002, 124, 13690–13691; g) Y. Onishi, T. Ito,
M. Yasuda, A. Baba, Eur. J. Org. Chem. 2002, 1578–1581; h)
Y. Onishi, T. Ito, M. Yasuda, A. Baba, Tetrahedron 2002, 58,
8227–8235; i) M. Yasuda, T. Saito, M. Ueba, A. Baba, Angew.
Chem. Int. Ed. 2004, 43, 711–714; j) T. Saito, M. Yasuda, A.
Baba, Synlett 2005, 1737–1739; k) T. Saito, Y. Nishimoto, M.
Yasuda, A. Baba, J. Org. Chem. 2006, 71, 8516–8522; l) T.
Saito, Y. Nishimoto, M. Yasuda, A. Baba, J. Org. Chem. 2007,
72, 8588–85900; m) Y. Nishimoto, M. Yasuda, A. Baba, Org.
Lett. 2007, 9, 4931–4934; n) Y. Nishimoto, M. Kajioka, T.
Saito, M. Yasuda, A. Baba, Chem. Commun. 2008, 6396–6398;
o) A. Baba, M. Yasuda, Y. Nishimoto, T. Saito, Y. Onishi, Pure
Appl. Chem. 2008, 80, 845–854; p) Y. Nishimoto, T. Saito, M.
Yasuda, A. Akio, Tetrahedron 2009, 65, 5462–5471.
See Supporting Information.
N. Sakai, T. Moriya, T. Konakahara, J. Org. Chem. 2007, 72,
5920–5922.
[7]
[8]
[9] K. Maeda, H. Shinokubo, K. Oshima, J. Org. Chem. 1997, 62,
6429–6431.
Received: April 8, 2010
Published Online: May 14, 2010
3386
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 3382–3386