Rhodium-catalysed 1,4-addition of diarylindium hydroxides to α,β-unsaturated carbonyl compounds

Article abstract of DOI:10.1039/b511779h

Diarylindium(III) hydroxides react with α,β-unsaturated carbonyl compounds in the presence of a rhodium catalyst to afford the 1,4-addition products in high yield. This reaction demonstrates the utility of diarylindium(III) hydroxide as an aryl source with rhodium catalysts. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b511779h

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Rhodium-catalysed 1,4-addition of diarylindium hydroxides to
a,b-unsaturated carbonyl compounds
Tomoya Miura and Masahiro Murakami*
Received (in Cambridge, UK) 19th August 2005, Accepted 15th September 2005
First published as an Advance Article on the web 13th October 2005
DOI: 10.1039/b511779h
carbonyl group was not observed. The reaction pathway is
Diarylindium(III) hydroxides react with a,b-unsaturated carbo-
nyl compounds in the presence of a rhodium catalyst to afford
the 1,4-addition products in high yield. This reaction demon-
strates the utility of diarylindium(III) hydroxide as an aryl
source with rhodium catalysts.
assumed to proceed as follows: the transmetalation between
organoindium reagent 2a and a rhodium catalyst produces the
arylrhodium intermediate A. Then, 1,4-addition of A to cyclohex-
2-en-1-one (1a) occurs to afford the rhodium enolate B, which is
hydrolysed by water to afford the product 3aa and
hydroxorhodium(I).
The transmetalation between a main-group organometallic reagent
and a transition metal catalyst is an important method to endow
the original organometallic reagent with a different character of
reactivities toward organic substrates. Indeed, a number of metal-
mediated synthetic reactions involve the transmetalation as a key
elementary step.1 Recently, the rhodium-catalysed addition reac-
tions of organometallic reagents to unsaturated functionalities
have emerged as a new and useful method for the formation of
carbon–carbon bonds under mild conditions.2 An organorhodium
intermediate generated by transmetallation from various organo-
metallics like organo-boron, -silicon and -tin is reactive enough to
add to a,b-unsaturated carbonyl compounds in a 1,4-fashion.3
On the other hand, organoindium(III) reagents have attracted
much attention as a carbon nucleophile source due to their high
chemoselectivity and low toxicity.4 In addition, organoindium(III)
reagents have a synthetic advantage in that they are readily
prepared from conventional organo-lithium and -magnesium
reagents and then directly employed in an ensuing reaction
without a need of anhydrous conditions because of their stability
in aqueous media. These desirable properties led us to examine the
rhodium-catalysed reaction of organoindium(III) reagents with
unsaturated organic functionalities. Herein, we report the
rhodium-catalysed 1,4-addition reaction of organoindium reagents
to a,b-unsaturated carbonyl compounds in aqueous media,
together with its extension to an asymmetric version.5,6 This
reaction demonstrates the utility of diarylindium(III) hydroxide as
an aryl source with rhodium catalysts.
When diphenylindium chloride was used instead of dipheny-
lindium hydroxide in dry THF, 3aa was obtained in ca. 10% yield,
although most of 1a was consumed. These contrasting results can
be explained by assuming that anionic ligands play an important
role in transmetalation of the Rh(I) species with an
indium(III)-phenyl linkage, and that a hydroxide anion is preferred
over a chloride anion in terms of the electron-donating ability, as
with the case of arylboronic acids.9
Results of the 1,4-addition of diarylindium hydroxides 2a–2e to
various a,b-unsaturated compounds 1a–1j (1 : 2 5 1 : 2) are
summarised in Table 1.{ The catalytic process worked well with a
sterically and electronically diverse array of diarylindium hydro-
xides 2b–2e to give the corresponding products 3ab–3ae (entries 1–
4). Reactions of enones 1b–1g, including cyclic enones, afforded
the b-phenylated ketones 3ba–3ga in good yield (entries 5–10).
Next, the 1,4-addition of 2a to a,b-unsaturated esters, amides and
nitriles was examined to expand the scope of the reaction. The
reaction with methyl crotonate (1h) was also successful (entry 11).
Crotonamide (1i) and crotononitrile (1j), whose reactivities are
relatively low, afforded the products in moderate yield (entries 12
and 13).
It should be noted that the use of chiral diene ligand 4,
developed by Carreira et al., led to the formation of 3aa in 97%
yield with a good enantioselectivity of 94% ee (eqn 1).10
Initially, diphenylindium hydroxide (2a) was prepared by
treatment of phenylmagnesium bromide (2.0 equiv.) with indium
trichloride (1.0 equiv.) in THF at room temperature for 30 min
followed by hydrolysis (10 min).7 A THF solution of cyclohex-2-
en-1-one (1a, 1.0 equiv.) and [Rh(OH)(cod)]2 (0.05 equiv. in Rh)
(cod 5 cycloocta-1,5-diene) were added successively to the
resulting reaction mixture, which was further stirred for 6 h at
room temperature. The 1,4-addition product 3aa was isolated in
82% yield after aqueous workup (Scheme 1).8 Formation of the
Heck-type unsaturated product or the 1,2-addition product to the
Department of Synthetic Chemistry and Biological Chemistry, Kyoto
University, Katsura, Kyoto, 615-8510, Japan.
E-mail: murakami@sbchem.kyoto-u.ac.jp; Fax: +81 75 383 2748;
Tel: +81 75 383 2747
Scheme 1
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Table 1 Rhodium-catalysed 1,4-addition of diarylindium hydroxides
ð1Þ
In summary, we have developed the rhodium-catalysed 1,4-
addition of organoindium reagents to a,b-unsaturated carbonyl
compounds, demonstrating the utility of diarylindium(III) hydro-
xide as an aryl source with rhodium catalysts.
Yield
Product 3 (%)a
Entry Substrate 1
2 (Ar)
1
2
3
4
1a
2b p-CH3C6H4 3ab
2c o-CH3C6H4 3ac
2d p-CH3OC6H4 3ad
94
99
77
85
This work was supported by Grant-in-Aid for Scientific
Research on Priority Areas 17035044 from The Ministry of
Education, Culture, Sports, Science and Technology (MEXT).
2e p-FC6H4
3ae
Notes and references
5
1b
2a
3ba
91
{ Indium trichloride (221 mg, 1.0 mmol) was placed in an oven-dried, Ar-
purged flask and dissolved with THF (1 mL). Arylmagnesium bromide
(1.0 M THF solution, 2.0 mL, 2.0 mmol) was added dropwise to the
solution at 0 uC. Then, the mixture was stirred at room temperature for
30 min to prepare diarylindium chloride. Water (0.5 mL) was added at 0 uC
to form a white suspension. After the suspension was stirred at room
temperature for 10 min, a solution of substrate 1 (0.5 mmol) in THF
(3.0 mL) and [Rh(OH)(cod)]2 (5.7 mg, 0.0125 mmol, 0.05 equiv of Rh) were
added. The resulting reaction mixture was further stirred for 6 h at room
temperature. Water (10 mL) was added, and the aqueous layer was
extracted with ethyl acetate (15 mL 6 3). The combined organic extracts
were dried over MgSO4. The solvent was removed under reduced pressure
and the residue was purified by preparative thin-layer chromatography
(hexane–ethyl acetate ) to give the product 3.
6
1c
2a
3ca
79
7
1d
1e
1f
2a
2a
2a
2a
2a
3da
3ea
3fa
3ga
3ha
88
73
85b
78
87
1 D. W. Knight in Comprehensive Organic Synthesis, ed. B. M. Trost and
I. Fleming, Pergamon Press, Oxford, 1991, vol. 3, pp. 481–520.
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tallic reagents, see: (a) [B]: Y. Takaya, M. Ogasawara, T. Hayashi,
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see: S. Araki, T. Shimizu, S-J. Jin and Y. Butsugan, J. Chem. Soc.,
Chem. Commun., 1991, 824.
6 For an example of Ni-catalysed 1,4-addition of triphenylindium(III), see:
I. Pe´rez, J. Pe´rez Sestelo, M. A. Maestro, A. Mourin˜o and
L. A. Sarandeses, J. Org. Chem., 1998, 63, 10074.
7 K. Takami, H. Yorimitsu, H. Shinokubo, S. Matsubara and K. Oshima,
Org. Lett., 2001, 3, 1997.
8
9
10
11
12
1g
1h
1i
1j
2a
2a
3ia
3ja
57c
8 The product 3aa was obtained in 62% yield and a small amount of 1a
remained when 1.0 equiv. of PhMgBr and 0.5 equiv. of InCl3 were used.
No reaction was observed without the rhodium catalyst.
9 (a) T. Huang, Y. Meng, S. Venkatraman, D. Wang and C.-J. Li, J. Am.
Chem. Soc., 2001, 123, 7451; (b) T. Hayashi, M. Takahashi, Y. Takaya
and M. Ogasawara, J. Am. Chem. Soc., 2002, 124, 5052.
13
40
10 C. Defieber, J.-F. Paquin, S. Serna and E. M. Carreira, Org. Lett., 2004,
6, 3873. See also: R. Shintani, T. Kimura and T. Hayashi, Chem.
Commun., 2005, 3213 and references therein.
a
b
Isolated yields. 3 equiv of 2a. 1i remained after workup.
c
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