Manganese-catalyzed insertion of aldehydes into a C-H bond

Article abstract of DOI:10.1002/anie.200702256

(Chemical Equation Presented) Mn gets in the game: In the presence of a manganese catalyst and a stoichiometric amount of hydrosilane, aldehydes insert into C-H bonds of aromatic rings of compounds with directing groups (see scheme). This first example of a manganese-catalyzed chemical transformation through C-H bond activation gives silyl ethers in good to excellent yields and can also be applied to asymmetric transformation.

Full text of DOI:10.1002/anie.200702256

Communications
DOI: 10.1002/anie.200702256
À
C H Activation
À
Manganese-Catalyzed Insertion of Aldehydes into a C H Bond**
Yoichiro Kuninobu,* Yuta Nishina, Takahiro Takeuchi, and Kazuhiko Takai*
Transition metals of the fourth row are abundant and cheap
compared to those of the fifth and sixth rows. Therefore, by
introducing new reactivities with fourth-row metal complexes,
it might be possible to replace fifth- and sixth-row metals in
some fundamental and important reactions. Catalytic
Grignard-type addition of nucleophiles to aldehydes is one
À
Scheme 1. Stoichiometric insertion of aldehyde into a C H bond.
TBAF= tetra-n-butylammonium fluoride
such reaction. Grignard reagents are usually prepared from
organic halides and magnesium metal,[1] but this procedure
results in the unwanted formation of stoichiometric amounts
of metal salts. One way to solve this problem is to generate the
To recycle the manganese complex, 2.0 equiv of triethyl-
silane (4) was added to the reaction mixture from the
beginning. As a result, silyl ether 5a was obtained in 93%
yield with 5 mol% [MnBr(CO)5].[8,9] We examined the
catalytic activity of several metal complexes using the
reaction between 1a, 2a, and 4 as a probe. A different
manganese complex, [Mn2(CO)10], showed similar catalytic
activities (82% yield of 5a). However, the reaction did not
proceed at all with the following metal complexes: [MnCl2],
[Mn(acac)3] (acac = acetylacetonate), [{ReBr(CO)3(thf)}2],[6]
[ReBr(CO)5], [Ru3(CO)12], [RuH2(CO)(PPh3)3], [RhCl-
(PPh3)3], and [Ir4(CO)12].[10]
nucleophiles by C H bond activation;[2] however, it has been
À
À
difficult to promote nucleophilic addition after the C H
activation step. Although nucleophilic addition of species
À
generated by C H activation has been reported using
ruthenium,[3] rhodium,[4] palladium,[5] and rhenium[6] catalysts,
it has been difficult to catalyze such reactions using fourth-
row transition-metal complexes.[7] We report herein that
1) complexes of manganese, a fourth-row transition metal,
À
can be employed for C H bond activation of aromatic
À
compounds; 2) insertion of aldehydes into C H bonds occurs
to give benzyl alcohols; and 3) catalytic transformation is
achieved with the manganese complex by the addition of
Et3SiH.
At the next stage, we investigated several aldehydes
(Table 1). Aromatic aldehydes with an electron-donating or
À
We initially investigated stoichiometric C H bond acti-
Table 1: Reactions between 1a and several aldehydes.[a]
vation and insertion of aldehydes with the manganese
complex [MnBr(CO)5]. A mixture of 1-methyl-2-phenyl-1H-
imidazole (1a) and [MnBr(CO)5] in toluene was heated at
1008C for 5 min, at which point a solution of benzaldehyde
(2a) was added. The mixture was heated at reflux for 10 h to
give alcohol 3 in 52% yield (Scheme 1). Although stoichio-
Entry
Substrate
R
Product
Yield [%][b]
À
metric C H bond activation and insertion of the aldehyde
1
2
2b
2c
2d
2e
p-(MeO)C6H4
p-(CF3)C6H4
o-MeC6H4
nC8H17
5b
5c
5d
5e
87 (89)
87 (89)
59 (60)
75 (79)
occured with [MnBr(CO)5], only a trace amount of 3 was
produced with a catalytic amount of the manganese complex.
3
4[c]
5[c]
2 f
5 f
56 (57)
[*] Dr. Y. Kuninobu, Y. Nishina, T. Takeuchi, Prof. Dr. K. Takai
Division of Chemistry and Biochemistry
Okayama University
6[d]
7
2g
2h
5g
5h
66 (67)
48 (50)
Tsushima, Okayama 700-8530 (Japan)
Fax: (+81)86-251-8094
E-mail: kuninobu@cc.okayama-u.ac.jp
ktakai@cc.okayama-u.ac.jp
[a] 2 (2.0 equiv); 4 (2.0 equiv). [b] Yield of isolated product. The yield
determined by 1H NMR spectroscopy is reported in parentheses.
[c] 1358C. [d] 48 h.
[**] Financial support by a Grant-in-Aid for Scientific Research on
Priority Areas (No. 18037049, “Advanced Molecular Transforma-
tions of Carbon Resources”) from the Ministry of Education,
Culture, Sports, Science, and Technology of Japan, and for Young
Scientists (B) (No. 18750088) from Japan Society for the Promotion
of Science, and Okayama Foundation for Science and Technology is
gratefully acknowledged. We thank Dr. Teruhiko Nitoda (The MS
Laboratory of Faculty of Agriculture, Okayama University) for
acquiring HR-MS spectra.
an electron-withdrawing group at the para position (2b and
2c) gave the corresponding silyl ethers in 87% yield (Table 1,
entries 1 and 2). Using an aldehyde with a methyl group at the
ortho position (2d), the yield of the silyl ether slightly
decreased, probably because of the steric hindrance (Table 1,
entry 3). By the reactions of alkyl aldehydes 2e and 2 f, the
corresponding silyl ethers 5e and 5 f were formed in 75% and
Supporting information for this article is available on the WWW
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56% yields, respectively (Table 1, entries 4 and 5). Hetero-
aromatic aldehydes 2g and 2h also provided the correspond-
ing silyl ethers 5g and 5h in moderate yields (Table 1,
entries 6 and 7).
To determine the reaction mechanism, we examined the
sequential transformation via intermediate 7 (Scheme 2).
and benzaldehyde (2a) with triethylsilane (4) in the presence
of manganese catalyst [MnBr(CO)5], an asymmetric reaction
proceeded, and a mixture of diastereomers of silyl ethers 9a
and 9b, respectively, was obtained in moderate diastereo-
meric excess (Table 2, entries 1 and 2). When we used
Table 2: Asymmetric reactions of chiral imidazoline 8 with 2 and 4.[a]
Entry
R
R’
Yield of product [%][b]
de [%]
1
2
3
4
Ph (8a)
PhCH2 (8b) Ph (2a)
iPr (8c)
iPr (8c)
Ph (2a)
9a
9b
9c
60
72
80
68
60
30
95
38
Ph (2a)
nC8H17 (2e) 9d
[a] 2 (2.0 equiv); 4 (2.0 equiv). [b] Yield of isolated product.
À
Scheme 2. Manganese-mediated insertion of aldehyde into a C H
bond.
imidazoline 8c bearing an isopropyl group at the stereogenic
center, the corresponding silyl ether 9c was provided in high
yield and diastereomeric excess (Table 2, entry 3). Using alkyl
aldehyde 2e, the diastereomeric excess of silyl ether 9d
decreased to 38% (Table 2, entry 4).
Treatment of 1a with a stoichiometric amount of the
manganese complex in toluene at 1008C for five minutes,
followed by addition of benzaldehyde (2a) and heating to
reflux for ten hours gave the possible intermediate 7. Then
hydrosilane 4 was added to the reaction mixture and further
heating resulted in the formation of silyl ether 5a in 58%
yield. This result indicates that hydrosilane 4 promotes
reductive elimination of manganese by silylation of an
alkoxy moiety.
In summary, we have succeeded in the insertion of an
À
aldehyde into a C H bond of an aromatic compound using a
manganese catalyst, [MnBr(CO)5]. In this reaction, the
polarity of the manganese–carbon bond in the intermediate
manganese complex is an important factor for promoting the
À
The proposed mechanism is as follows (Scheme 3):
1) oxidative addition of an aromatic compound to a manga-
insertion of aldehydes (polar molecules) into the C H bond.
This reaction could be applied to asymmetric transformation
using an aromatic compound with a chiral substituent.
Further insertion reactions, promoted by manganese com-
À
plexes, of polar molecules into a C H bond are currently
being investigated.
Experimental Section
A mixture of aromatic compound 1 or 8 (0.250 mmol), aldehyde 2
(0.500 mmol), hydrosilane 4 (0.500 mmol), [MnBr(CO)5] (3.4 mg,
0.0125 mmol), and toluene (1.0 mL) was stirred at 1158C for 24 h. The
product was isolated by column chromatography on silica gel, using
hexane/ethyl acetate 3:1 as eluent, to give 5 or 9.
Received: May 22, 2007
À
Keywords: aldehydes · asymmetric synthesis · C H activation ·
manganese · silyl ethers
.
Scheme 3. Proposed mechanism for the formation of silyl ethers.
[11]
À
nese center (C H bond activation);
2) insertion of an
[1] For a book of Grignard reactions, see: Grignard Reagents: New
Developments (Ed.: H. G. Richey), Wiley, New York, 2000;
Handbook of Grignard Reagents (Eds.: G. S. Silverman, P. E.
Rakita), Marcel Dekker, New York, 1996.
[2] For a review, see: a) F. Kakiuchi, S. Murai, Top. Organomet.
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Angew. Chem. 1999, 111, 1808 – 1822; Angew. Chem. Int. Ed.
aldehyde into the manganese–carbon (aryl) bond. In this step,
the polarity of the manganese–carbon bond is an important
factor affecting the insertion of the aldehyde (a polar
À
molecule) into the C MnH bond; 3) silyl protection via the
formation of dihydrogen.
This reaction could also be applied to asymmetric trans-
formation.[12] By the reaction of chiral imidazolines 8a and 8b
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Communications
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[9] 4,5-Dihydro-1-methyl-2-phenyl-1H-imidazole 1b also afforded
the corresponding silyl ether 6 in 72% yield.
[3] N. Chatani, Y. Ie, F. Kakiuchi, S. Murai, J. Org. Chem. 1997, 62,
2604 – 2610.
[4] a) P. Hong, H. Yamazaki, K. Sonogashira, N. Hagihara, Chem.
Lett. 1978, 535 – 538; b) M. Tanaka, T. Sakakura, Y. Tokunaga, T.
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[10] For iridium-catalyzed coupling of imidazoles with aldehydes in
the presence of a hydrosilane, see: Y. Fukumoto, K. Sawada, M.
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[11] Another possibility is that the reaction is catalyzed by only a
manganese(I) species. There has been a report on the formation
of manganese(I) complex 10 by treatment of 1a with [Mn-
(CH3)(CO)5], see: A. Suꢀrez, J. M. Vila, M. T. Pereira, E.
Gayoso, M. Gayoso, J. Organomet. Chem. 1987, 335, 359 – 363.
We examined the reaction between 1a, 2a, and 4 using [Mn-
(CH3)(CO)5] as a catalyst. We found that the reaction pro-
ceeded, and 5a was obtained in 85% yield. This result indicates
that the active species of the reaction would be MnI. However, in
the reaction reported herein, the active species derived from
[MnBr(CO)5] will not be the same as that derived from
[Mn(CH3)(CO)5]. Therefore, it is still not clear whether the
real active species is Mn(I) or Mn(III), and further investigation
is required.
[7] Nucleophilic addition with fourth-row metal complexes by
À
catalytic C H activation is still rare. However, there are several
examples of the insertion of nonpolar unsaturated molecules
À
initiated by C H fission with complexes of fourth-row metals,
see: a) Co: G. Halbritter, F. Knoch, H. Kisch, J. Organomet.
Chem. 1995, 492, 87 – 98; b) Ni: Y. Nakao, K. S. Kanyiva, S. Oda,
T. Hiyama, J. Am. Chem. Soc. 2006, 128, 8146 – 8147.
[8] Investigation of hydrosilanes: triethylsilane 93%; diethylme-
thylsilane 59%, dimethylphenylsilane 53%; triphenylsilane
77%. This reaction did not proceed using the following silanes:
diphenylsilane, tris(trimethylsilyl)silane, hexamethyldisilane,
hexamethyldisilazane.
[12] For an example of transition-metal-catalyzed enantioselective
À
functionalization via C H bond activation, see: S. J. OꢁMalley,
K. L. Tan, A. Watzke, R. G. Bergman, J. A. Ellman, J. Am.
Chem. Soc. 2005, 127, 13496 – 13497.
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