Generation of allylic indium by hydroindation of 1,3-dienes and one-pot reaction with carbonyl compounds

Article abstract of DOI:10.1021/ol061797n

A hydroindation of 1,3-dienes by dichloroindium hydride (HInCl₂) generates allylic indiums that react with carbonyl or imine moieties in a one-pot treatment. The former reaction proceeds in a radical manner, and the latter is ionic allylation.

Full text of DOI:10.1021/ol061797n

ORGANIC
LETTERS
2
006
Vol. 8, No. 20
553-4556
Generation of Allylic Indium by
Hydroindation of 1,3-Dienes and
One-Pot Reaction with Carbonyl
Compounds
4
†
†
†
,‡
Naoki Hayashi, Hiroyuki Honda, Makoto Yasuda, Ikuya Shibata,* and
Akio Baba*
,
†
Research Center for EnVironmental PreserVation, Osaka UniVersity,
-4 Yamadaoka, Suita, Osaka 565-0871, Japan, and Department of Applied Chemistry,
2
Graduate School of Engineering, Osaka UniVersity, 2-1 Yamadaoka, Suita,
Osaka 565-0871, Japan
shibata@epc.osaka-u.ac.jp; baba@chem.eng.osaka-u.ac.jp
Received July 21, 2006
ABSTRACT
2
A hydroindation of 1,3-dienes by dichloroindium hydride (HInCl ) generates allylic indiums that react with carbonyl or imine moieties in a
one-pot treatment. The former reaction proceeds in a radical manner, and the latter is ionic allylation. Moreover, both reactions require no
additives such as radical initiators, Lewis acids, or transition metal catalysts.
Much attention has been paid to the generation of charac-
teristic allylic metals and their reactions with various
electrophiles. In particular, an important subject is the
include subsequent one-pot allylations by the generated metal
3a,b
species without any additives. Borohydrides are plausibly
the most versatile reagents, but control of the reactivity is
1
3
a
generation of multisubstituted active allylic metals, which
can lead to tertiary or quaternary carbon centers by reactions
with carbon electrophiles. One of the practical methods is a
hydrometalation of 1,3-dienes. This method provides an
atom-economical reaction system and can be applied to
various substituted allylic species. A conventional method
by transmetalation using allylic metals such as the Grignard
not so easy. Recently, allylic indium reagents have been
recognized because of their environmentally benign character
4
that includes water tolerance. However, there is no report
about the generation of allylic indiums by the hydroindation
of 1,3-dienes.
(3) (a) Brown, H. C.; Liotta, R.; Kramer, G. W. J. Org. Chem. 1978,
reagent is not appropriate for this purpose.1a,2 Although a
43, 1058-1063. (b) Collins, S.; Dean, W. P.; Ward, D. G. Organometallics
1
1
988, 7, 2289-2293. (c) Kira, M.; Hino, T.; Sakurai, H. Tetrahedron Lett.
989, 30, 1099-1102. (d) Satoh, M.; Nomoto, Y.; Miyaura, N.; Suzuki,
number of reports have been presented for the hydrometa-
lation of 1,3-dienes, most required the assistance of transition
A. Tetrahedron Lett. 1989, 30, 3789-3792. (e) Kobayashi, S.; Nishio, K.
Synthesis 1994, 457-459. (f) Masuyama, Y.; Tsunoda, M.; Kurusu, Y. J.
Chem. Soc., Chem. Commun. 1994, 1451-1452. (g) Gao, Y.; Urabe, H.;
Sato, F. J. Org. Chem. 1994, 59, 5521-5523. (h) Kobayashi, S.; Nishio,
K. J. Org. Chem. 1994, 59, 6620-6628. (i) Sell, M. S.; Klein, W. R.; Rieke,
R. D. J. Org. Chem. 1995, 60, 1077-1080. (j) Takai, K.; Matsukawa, N.;
Takahashi, A.; Fujii, T. Angew. Chem., Int. Ed. 1998, 37, 152-155. (k)
Takai, K.; Toratsu, C. J. Org. Chem. 1998, 63, 6450-6451. (l) Bareille,
L.; Gendre, P. L.; Moise, C. Chem. Commun. 2005, 775-777. More
recently, the generation of allylic indium from diene by Ni catalyst was
reported. See: (m) Hirashita, T.; Kambe, S.; Tsuji, H.; Araki, S. Chem.
Commun. 2006, 2595-2597.
3
metal catalysts. Moreover, there are a few methods that
†
Department of Applied Chemistry, Graduate School of Engineering.
Research Center for Environmental Preservation.
‡
(
1) (a) Yamamoto, Y.; Asao, N. Chem. ReV. 1993, 93, 2207-2293. (b)
Roush, W. R. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming,
I., Eds.; Pergamon Press: Oxford, UK, 1991; Vol. 2, Chapter 1.1, p 1.
(
2) (a) Thomas, E. J. Chem. Commun. 1997, 411-418. (b) Marshall, J.
A. Chem. ReV. 1996, 96, 31-47. (c) Nishigaichi, Y.; Takuwa, A.
Tetrahedron 1993, 49, 7395-7426.
1
0.1021/ol061797n CCC: $33.50
© 2006 American Chemical Society
Published on Web 09/02/2006

We have recently developed the generation and synthetic
use of dihaloindium hydrides (HInX ). Indium hydride has
2
promoted at the γ-position of the resulting allylic indium
(eq 1). Internal dienes such as cyclohexadiene and 1,4-
diphenyl-1,3-butadiene were found to be inert to the hydro-
indation because predominant reduction of aldehyde by
5
effected not only some ionic reductions6 of carbonyl
compounds but also radical reactions such as dehalogenation
and hydroindation of alkynes.7 In the course of our
investigation, dihaloindium hydrides were found to promote
radical conjugate addition to 1,3-dienes. Herein we report
the generation of allylic indium species and subsequent one-
pot allylation of aldehydes, ketones, and imines to produce
tertiary and quaternary carbon centers, in which both steps
require no promoters. This is the first example of radical
hydroindation of 1,3-dienes to furnish multisubstituted allylic
indiums.
,8
2
HInCl took place instead of allylation.
Next, we investigated the reactions of diene 1a with
various electrophiles under the optimized conditions. The
reactions with benzaldehyde derivatives bearing either
electron-donating or electron-withdrawing substituents gave
the corresponding products in good yields (entries 2-6 in
2
First, to optimize the reaction conditions, 2,3-dimethyl-
1
,3-butadiene (1a) was treated with HInCl
the effective transmetalation between InCl
2
generated from
9
3
3
and Bu SnH,
and subsequently benzaldehyde (2a) was added to the
resulting mixture under various conditions. In this system,
the generation of a prenyl type of indium species is expected
to produce the adduct 3a possessing a quaternary carbon
center. Under the optimized conditions, treating 2 equiv of
Table 2). The reducible functionalities such as Cl, NO , and
Table 2. Allylation of Various Electrophilesa
HInCl
temperature, a quantitative yield of 3a was obtained (entry
in Table 1). The selective formation of 3a plausibly
2
with an excess amount of the 1,3-diene at room
3
Table 1. Hydroindation of 1,3-Diene and One-Pot Allylation
a
Diene (4 mmol), HInCl2 (2 mmol), electrophile (1 mmol), THF solvent
(
2 mL). b HInCl2 (3 mL) and THF solvent (3 mL) were used. The period
c
of reaction between allylic indium and 2h was 16 h. The period of reaction
suggests that 1,4-addition of indium hydride to the 1,3-diene
between allylic indium and 2i was 16 h. d The period of reaction between
1a took place and the subsequent allylation of aldehyde was
1a with HInCl2 was 14 h.
(
4) (a) Cintas, P. Synlett 1995, 1087-1096. (b) Marshall, J. A.
Chemtracts: Org. Chem. 1997, 10, 481-496. (c) Li, C.-J.; Chan, T.-H.
Tetrahedron 1999, 55, 11149-11176. (d) Araki, S.; Hirashita, T. In Main
Group Metals in Organic Synthesis; Yamamoto, H., Oshima, K., Eds.;
Wiley-VCH: Weinheim, 2004; Vol. 1, pp 323-386.
methoxycarbonyl groups tolerated the conditions. Moreover,
aliphatic aldehyde 2g also afforded allylated product 3g in
8
2
8% yield (entry 7). Although 3 equiv of HInCl and a long
(5) Baba, A.; Shibata, I. Chem. Rec. 2005, 5, 323-335.
(
6) (a) Miyai, T.; Inoue, K.; Yasuda, M.; Shibata, I.; Baba, A.
reaction period were needed, aromatic ketone 2h gave
moderate yields (entries 8). Imine 2j also reacted in moderate
yield after a long reaction period (entry 10). Unfortunately,
aliphatic ketone 2i gave a low yield (entry 9). We speculated
that these results depended on the low nucleophilicity of
sterically demanding γ-disubstitued allylic indium species
generated in situ.
In the next stage we examined the reactions of 1,3-
butadiene (1d) in which the formation of less substi-
tuted crotyl indium was expected to lead to facile reaction
Tetrahedron Lett. 1998, 39, 1929-1932. (b) Shibata, I.; Kato, H.; Ishida,
T.; Yasuda, M.; Baba, A. Angew. Chem., Int. Ed. 2004, 43, 711-713.
(
7) (a) Inoue, K.; Sawada, A.; Shibata, I.; Baba, A. Tetrahedron Lett.
2
001, 42, 4661-4663. (b) Inoue, K.; Sawada, A.; Shibata, I.; Baba, A. J.
Am. Chem. Soc. 2002, 124, 906-907. (c) Hayashi, N.; Shibata, I.; Baba,
A. Org. Lett. 2004, 6, 4981-4983. (d) Hayashi, N.; Shibata, I.; Baba, A.
Org. Lett. 2005, 7, 3093-3096.
(
8) Takami, K.; Yorimitsu, H.; Oshima, K. Org. Lett. 2002, 4, 2993-
2
995.
9) Here we selected the InCl3/Bu3SnH system, which generates HInCl2
(
effectively compared to other hydride sources such as NaBH4 and Et3SiH.
In the case of other hidride sources, slow generation of HInCl2 and side
reactions became problematic.
4554
Org. Lett., Vol. 8, No. 20, 2006

with ketones. As expected, the subsequent reactions with
aromatic and aliphatic ketones and an imine proceeded
smoothly to give the corresponding allylation products in
good yields (entries 3-5 in Table 3). Even alkyl ketone 2i
the direct reaction of imine with allylic metals generated by
hydrometalation of 1,3-diene.
Table 3. Reaction with 1,3-Butadiene and Isoprenea
To confirm the reaction, the effect of radical inhibitor
(TEMPO) was examined by changing the timing of the
addition (Scheme 1). When TEMPO was added before the
Scheme 1a
a
HInCl /TEMPO/diene/aldehyde ) 2/0.1/4/1 (equiv), THF
2
solvent.
incorporation of 1,3-dienes, only the reduction of benzalde-
hyde (2a) to benzyl alcohol (4) was promoted without the
formation of allylated products. Thus the hydroindation of
the diene was apparently supressed by TEMPO. In contrast,
when TEMPO was added after the completion of hydro-
indation, the allylated product 3a was obtained effectively.
No inhibition of allylation of aldehyde took place. These
results indicate that the present system includes both radical
hydroindation and ionic allylation steps. A plausible reaction
course is shown in Scheme 2. Dichloroindium radical is
a
Diene (4 mmol), HInCl2 (2 mmol), electrophile (1 mmol), THF solvent
b
c
(
2 mL). A excess amount of 1,3-butadiene was used. Byproduct 3s was
obtained in 12% yield.
Scheme 2
gave a higher yield of 69%, whereas little allylation adduct
was obtained from 2,3-dimethyl-1,3-butadiene (entry 9 in
Table 2 vs entry 4 in Table 3). Unfortunately, the stereose-
lectivities are not high, furnishing mixtures of anti and syn
isomers.
In the case of isoprene, the reaction with benzaldehyde
(2a) gave a mixture of expected adduct 3p (75%) along with
2,2-dimethylallylic alcohol 3s (12%) (entry 6). On the other
hand, when ketone 2h and imine 2j were treated, only the
former type of adducts 3q and 3r were obtained (entries 7
and 8). These results indicate that two types of allylic
indiums, A and B, were generated, and both reacted with
aldehyde to give 3p and 3s, respectively, as a result of the
high reactivity of aldehyde (eq 2). In contrast, less reactive
ketone 2h and imine 2j reacted with only the less bulky
species A. As far as we know, this is the first example of
7
a
generated by homolytic cleavage of the In-H bond. Next,
the indium radical adds to the terminal position of 1,3-dienes
to give allylic radical C, which is hydrogenated by HInCl
into allylic indium D along with regeneration of indium
radical. The reaction between the resulting allylic indium
and aldehydes proceeds in an ionic manner. Since the
2
Org. Lett., Vol. 8, No. 20, 2006
4555

nucleophilic addition occurs at the γ-carbon in the allylic
indium, the reactivity depends on the steric hindrance around
the γ-carbon.
Acknowledgment. This research has been carried out at
the “Handai Frontier Research Center” and was supported
by the center of excellence (21COE) program “Creation of
Integrated EcoChemistry” of Osaka University and a Grant-
in-Aid for Scientific Research from the Ministry of Educa-
tion, Science, Sports, and Culture.
In conclusion, we have developed a novel one-pot reaction
in which the generation of allylic indiums by hydroindation
of 1,3-dienes was followed by successive allylation of
electrophiles such as aldehydes, ketones, and imine. The
former proceeds in a radical manner, and the latter includes
an inonic process. Both the hydroindation and allylation steps
required no assistance of either radical initiator, transition
metal catalysts, or Lewis acids. Further applications of
present reaction will be reported in the near term.
Supporting Information Available: Experimental details
and characterization data. This material is available free of
charge via the Internet at http://pubs.acs.org.
OL061797N
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Org. Lett., Vol. 8, No. 20, 2006