Ruthenium-Catalyzed Regioselective α-Alkylation of Ketones: The First Alkyl-Group Transfer from Trialkylamines to the α-C Atom of Ketones

Full text of DOI:10.1002/1521-3773(20010302)40:5<958::AID-ANIE958>3.0.CO;2-4

COMMUNICATIONS
[
8] a) G. Gonzalez, P. Lahuerta, M. Martinez, E. Peris, M. Sanau, J. Chem.
Soc. Dalton Trans. 1994, 545; b) F. Estevan, G. Gonzalez, P. Lahuerta,
M. Martinez, E. Peris, R. van Eldik, J. Chem. Soc. Dalton Trans. 1996,
Ruthenium-Catalyzed Regioselective a-
Alkylation of Ketones: The First Alkyl-Group
Transfer from Trialkylamines to the a-C Atom
of Ketones**
1
045.
9] P. Lahuerta, J. Pay a , M. A. Pellinghelli, A. Tiripiccio, Inorg. Chem.
992, 31, 1224.
[
1
[
[
10] R. D. Holmes-Smith, R. D. Osei, S. R. Stobart, J. Chem. Soc. Perkin.
Trans. 1 1983, 861.
11] T. Maschmeyer, R. D. Oldroyd, G. Sankar, J. M. Thomas, I. J.
Shannon, J. A. Klepetko, A. F. Masters, J. K. Beattie, C. R. A. Catlow,
Angew. Chem. 1997, 109, 1713; Angew. Chem. Int. Ed. Engl. 1997, 36,
Chan Sik Cho,* Bok Tae Kim, Myung Jin Lee,
Tae-Jeong Kim, and Sang Chul Shim*
Homogeneous ruthenium-catalyzed organic reactions have
been introduced for a wide variety of organic transformations
and syntheses.[ In the course of our continuing studies on
transition metal-catalyzed synthesis of N-heterocyclic com-
pounds, we recently developed and reported a ruthenium-
1
639.
12] a) F. J. Feher, D. A. Newman, J. F. Waltzer, J. Am. Chem. Soc. 1989,
11, 1741; b) T. Maschmeyer, M. C. Klunduk, C. M. Martin, D. S.
Shephard, J. M. Thomas, B. F. G. Johnson, Chem. Commun. 1997,
847; c) J. M. Thomas, G. Sankar, M. C. Klunduk, M. P. Attfield, T.
Maschmeyer, B. F. G. Johnson, R. G. Bell, J. Phys. Chem. B 1999, 103,
809; d) H. C. L. Abbenhuis, Chem. Eur. J. 2000, 6, 25.
13] V. Ruffieux, G. Schmid, P. Braunstein, J. Ros e , Chem. Eur. J. 1997, 3,
00.
1]
[
1
1
[2]
catalyzed synthetic approach for the formation of indoles
and quinolines[ by alkyl-group transfer from trialkylamines
3]
8
[
[
[
[4]
to anilines (amine-exchange reaction ). While studying the
9
ruthenium-catalyzed heteroannulation between 4-aminoace-
tophenone and triallylamine, we found unexpectedly that
careful analysis of the crude reaction mixture revealed a small
amount of 1-(2-ethyl-3-methylquinolin-6-yl)pentan-1-one
14] F. A. Cotton, R. A. Walton, Multiple Bonds Between Metal Atoms, 2nd
ed., Oxford University Press, Oxford, 1993.
15] Crystal data for endo-5: C75
H
104
O
20
P
2
Rh
2
Si
8
, M
w
ˆ 1818.06, pink plate,
Å
0
3
.30  0.18  0.10 mm, triclinic, space group P1, a ˆ 12.003(1), b ˆ
4.795(1), c ˆ 10.306(1) Š, a ˆ 91.76(1), b ˆ 98.82(1), g ˆ 86.19(1)8,
(
2%) in addition to the expected product 1-(2-ethyl-3-
3
� 3
Vˆ 4243.0(6) Š , Z ˆ 2,
1
calcd ˆ 1.423 gcm
; Rigaku R-Axis IIC
methylquinolin-6-yl)ethanone [Eq. (1); dppm ˆ bis(diphe-
diffractometer, 2qmax ˆ 50.368, MoKa radiation, l ˆ 0.71073 Š, Tˆ
nylphosphanyl)methane].[ Presumably, the former quino-
3a]
1
80(2) K; of 24851 measured reflections, 14357 were independent
and 10214 observed with I > 2s(I), 0 ꢀ h ꢀ 14, � 41 ꢀ k ꢀ 41, � 12 ꢀ
l ꢀ 12; R ˆ 0.0506, wR ˆ 0.1100, GOF ˆ 0.993 for 967 parameters,
�
3
D1max ˆ 0.811 eŠ . The structure was solved by direct methods
2
(
(
SHELXS-97) and developed by least-squares refinement on jF j
SHELXL97). All non-hydrogen atoms were refined anisotropically,
and hydrogen atoms were placed in calculated positions. Crystallo-
graphic data (excluding structure factors) for the structure reported in
this paper have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication no. CCDC-149158. Copies
of the data can be obtained free of charge on application to CCDC, 12
Union Road, Cambridge CB21EZ, UK (fax: (‡44)1223-336-033;
e-mail: deposit@ccdc.cam.ac.uk).
[
16] a) A. R. Chakravarty, F. A. Cotton, D. A. Tocher, J. H. Tocher,
Organometallics 1985, 4, 8; b) F. Estevan, P. Lahuerta, J. Perez-Prieto,
M. Sanau, S.-E. Stiriba, M. A. Ubeda, Organometallics 1997, 16, 880;
c) D. F. Taber, S. C. Malcolm, K. Bieger, P. Lahuerta, M. Sanau, S.-E.
Stiriba, J. Perez-Prieto, M. A. Monge, J. Am. Chem. Soc. 1999, 121,
line was formed by alkylation of the latter.[5] These observa-
tions led us to seek a general method for the ruthenium-
catalyzed a-alkylation of ketones with trialkylamines. In sharp
contrast to the aforementioned amine-exchange reaction, alkyl-
group transfer from trialkylamines to the a-carbon atom of
ketones is unprecedented. Here we report on a general method
for alkyl-group transfer from trialkylamines to the a-carbon
atom of ketones in the presence of a ruthenium catalyst.
First, we examined the alkylation of acetophenone (1a)
with tributylamine (2a) with various ruthenium catalyst
precursors [Eq. (2)]. Typically, 1a was treated with an
8
60.
[
[
[
17] M. O. Farrell, C. H. van Dyke, L. J. Boucher, S. J. Metlin, J. Organo-
met. Chem. 1979, 172, 367.
18] a) L. T. Zhuralev, Colloids Surf. 1993, 74, 71; b) P. Basu, D. Panayotov,
J. T. Yates, Jr., J. Am. Chem. Soc. 1988, 110, 2074.
19] P and Rh contents of the modified silica supports are estimates based
on the assumption of complete adsorption since varying contents of
physisorbed water severely affected the accuracy of elemental analysis
data. Thus, an inaccuracy of Æ10% has to be considered.
[*] Dr. C. S. Cho, Prof. Dr. S. C. Shim, B. T. Kim, M. J. Lee,
Prof. Dr. T.-J. Kim
Department of Industrial Chemistry
College of Engineering
Kyungpook National University
Taegu 702-701 (Korea)
Fax : (‡82)53-959-5586
E-mail: scshim@kyungpook.ac.kr
[
**] This work was supported by the Basic Research Program of the Korea
Science and Engineering Foundation (2000-2-12200-001-3). C.S.C.
gratefully acknowledges a Post-Doctoral Fellowship of Kyungpook
National University (2000).
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
958
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4005-0958 $ 17.50+.50/0
Angew. Chem. Int. Ed. 2001, 40, No. 5

COMMUNICATIONS
Given these results, several ketones and amines were
screened with these catalysts (Table 2). Alkyl aryl ketones 1a
and 1b were readily alkylated with a variety of trialkylamines
2
a ± 2e to afford a-alkylated ketones 3a ± 3 f in moderate to
[6]
good yields. No a,a-dialkylation was observed. A fivefold
excess of amine relative to the substrate was required for the
reaction of 1b, in which case the reaction became slower and
the yield was lower.[ Higher reaction rate and yield were
observed with the benzo-fused cyclic ketone 1-indanone (1c).
To test for regioselectivity, dialkyl ketones 1d and 1e were
employed, and alkylation took place exclusively at the less
hindered methyl group.[ The reaction of 4-phenylcyclohex-
anone (1 f) with 2a gave not only 2-butyl-4-phenylcyclohex-
anone (3p) but also a small amount of 2,6-dibutyl-4-phenyl-
cyclohexanone (13% yield). The reaction of a,b-unsaturated
ketones such as trans-4-phenyl-3-buten-2-one with 2a gave no
alkylated product, and the starting material was recovered.
Replacing amines with imines as alkylating agent was
successful and gave the expected products [Eqs. (3) and (4)].
equimolar amount of 2a in dioxane in the presence of a
ruthenium catalyst precursor (5 mol%) at 1808C for 40 h to
afford 1-phenylhexan-1-one (3a). Table 1 shows that RuCl3 ´
nH O/PPh and [RuCl (PPh ) ] are the systems of choice for
7]
2
3
2
3 3
Table 1. Ruthenium-catalyzed a-butylation of 1a with 2a [Eq. (2)].[a]
Entry
Catalyst precursor
Conversion [%]
Yield [%]
of 3a
8]
of 1a[
b]
[b]
1
2
3
4
5
6
7
RuCl
RuCl
3
3
´ nH
´ nH
2
O/3PPh
3
77
32
90
23
25
4
70
19
69
10
4
O/1.5dppm[
c]
2
[RuCl
[RuH
[Ru (CO)12
[Cp*RuCl
(CO)][
[Cp*RuCl(CO)(PEt
2
(PPh
3 3
) ]
) ]
3 4
2
(PPh
3
]
d]
2
3
0
)][d]
3
1
[
a] Reaction conditions: 1a (1 mmol), 2a (1 mmol), ruthenium catalyst
(
5 mol%), 1,4-dioxane (10 mL), 1808C, 40 h, under Ar. [b] Determined by
5
GLC. [c] dppm ˆ bis(diphenylphosphanyl)methane. [d] Cp* ˆ h -C
5 5
Me .
effective alkylation (entries 1 and 3). The difference between
conversion and product yield could be due to reductive
amination of the ketone to give a secondary amine as side
product.
Table 2. Ruthenium-catalyzed a-alkylation of ketones 1 with trialkyl-
amines 2.[
a]
Ketone
R
3
N
Product
Yield
Here both yields and the type of the product depend upon the
imine employed. For instance, imines 4 gave a single
alkylation product, while imine 5 yielded two products (3a
and 3e) that resulted from the transfer of the alkyl or the
alkylidene substituent on nitrogen. The formation of 3e may
be explained by the generation of (benzyl)(butyl)amine by
reduction of the PhCˆN bond under the reaction conditions
[
b]
[%]
2
2
2
2
2
a R ˆ Bu
3a R ˆ Bu
61
73
77
b R ˆ hexyl
c R ˆ iBu
3b R ˆ hexyl
3c R ˆ iBu
d R ˆ isopentyl
e R ˆ benzyl
3d R ˆ isopentyl 67
3e R ˆ benzyl
30
32[c]
employed. In fact, in a separate experiment the alkylation of
2
a
3 f
1
a with N-butylbenzylamine afforded 3a and 3e in 11% and
2
2
2
2
a
b
c
3g R ˆ Bu
3h R ˆ hexyl
3i R ˆ iBu
83
89
83
38% yields, respectively.
In summary, we have developed a novel ruthenium-
catalyzed highly regioselective a-alkylation of ketones with
an array of trialkylamines and imines. The present ruthenium-
catalyzed alkylation is a first example of alkyl-group transfer
from trialkylamines and imines to the a-carbon atom of
ketones. The reaction mechanism[
d
3j R ˆ isopentyl 88
2
2
2
2
a
b
c
3k R ˆ Bu
3l R ˆ hexyl
3m R ˆ iBu
70
78
75
9, 10]
and synthetic applica-
d
3n R ˆ isopentyl 78
tions are currently under investigation.
2
2
a
a
3o
3p
81[d]
Experimental Section
48[e,f]
Typical procedure: 1a (0.24 g, 2.0 mmol), 2a (0.37 g, 2.0 mmol), RuCl
nH (0.026 g, 0.10 mmol), PPh (0.079 g, 0.30 mmol), and dioxane
10 mL) were placed in a 50-mL autoclave and allowed to react under
argon at 1808C for 40 h. The reaction mixture was filtered through a short
silica gel column (CHCl ), washed with 50 mL of 5% HCl and dried over
Na SO . Removal of the solvent left an oil, which was purified by column
3
´
2
O
3
(
[
a] Reaction conditions: 1 (2 mmol), 2 (2 mmol), RuCl
3
´ nH
2
O (5 mol%),
3
PPh
3
(15 mol%), 1,4-dioxane (10 mL), 1808C, 40 h, under Ar. [b] Yield of
2
4
isolated product. [c] Carried out in a molar ratio of 2a:1b ˆ 5:1. [d] Yield
chromatography (ethyl acetate:hexane 1:15) to give 1-phenylhexan-1-one
(3a) in 61% yield.
determined by GLC. [e] Mixture of diastereoisomers (1:5). [f] 2,6-Dibutyl-
4-phenylcyclohexanone (isomer ratio 81:13:6) was also isolated in 13%
yield.
Received: October 2, 2000 [Z15884]
Angew. Chem. Int. Ed. 2001, 40, No. 5
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4005-0959 $ 17.50+.50/0
959

COMMUNICATIONS
[
1] Recent reviews: a) M. A. Bennet, T. W. Matheson in Comprehensive
Organometallic Chemistry, Vol. 4 (Eds.: G. Wilkinson, F. G. A. Stone,
E. W. Abel), Pergamon, Oxford, 1982, pp. 931 ± 965; b) S. Murai, F.
Kakiuchi, S. Sekine, Y. Tanaka, A. Kamatani, M. Sonoda, N. Chatani,
Pure Appl. Chem. 1994, 66, 1527 ± 1534; c) S.-I. Murahashi, Angew.
Chem. 1995, 107, 2670 ± 2693; Angew. Chem. Int. Ed. Engl. 1995, 34,
Half-Metallocene Tantalum Complexes
Bearing Methyl Methacrylate (MMA) and
1,4-Diaza-1,3-diene Ligands as MMA
Polymerization Catalysts**
2
9
3
443 ± 2465; d) T. Naota, H. Takaya, S.-I. Murahashi, Chem. Rev. 1998,
8, 2599 ± 2660; e) S.-I. Murahashi, H. Takaya, Acc. Chem. Res. 2000,
3, 225 ± 233.
Yutaka Matsuo, Kazushi Mashima,* and Kazuhide Tani
Well-defined organometallic complexes were recently re-
ported to be single-site catalysts for the polymerization of
[
2] a) C. S. Cho, H. K. Lim, S. C. Shim, T. J. Kim, H.-J. Choi, Chem.
Commun. 1998, 995 ± 996; b) C. S. Cho, J. H. Kim, S. C. Shim,
Tetrahedron Lett. 2000, 41, 1811 ± 1814.
[1]
various monomers. While enolate complexes of zirconi-
um,[
2±5]
yttrium, and samarium,
[6]
[7, 8]
as well as aluminum
[
3] a) C. S. Cho, B. H. Oh, S. C. Shim, Tetrahedron Lett. 1999, 40, 1499 ±
1
500; b) C. S. Cho, B. H. Oh, S. C. Shim, J. Heterocycl. Chem. 1999, 36,
[9]
[10]
enolate complexes with Schiff base or porphyrin ligands,
have been reported to be active initiators for the polymer-
ization of polar olefinic monomers such as methyl acrylate
(MA) and methyl methacrylate (MMA), enolate complexes
of other transition metals have not been utilized. We sought a
new metal enolate complex that can initiate polymerization of
these polar monomers. Since Group 5 metals tolerate polar
functional groups and are less oxophilic than the metals of
Groups 3 and 4, we chose half-metallocene complexes of
tantalum, cationic alkyl and alkylidene derivatives of which
have already been applied in the living polymerization of
1
175 ± 1178; c) C. S. Cho, J. S. Kim, B. H. Oh, T.-J. Kim, S. C. Shim,
N. S. Yoon, Tetrahedron 2000, 56, 7747 ± 7750; d) C. S. Cho, B. H. Oh,
J. S. Kim, T.-J. Kim, S. C. Shim, Chem. Commun. 2000, 1885 ± 1886.
4] For transition metal-catalyzed amine-exchange reactions, see a) N.
Yoshimura, I. Moritani, T. Shimamura, S.-I. Murahashi, J. Am. Chem.
Soc. 1973, 95, 3038 ± 3039; b) S.-I. Murahashi, T. Hirano, T. Yano, J.
Am. Chem. Soc. 1978, 100, 348 ± 350; c) Y. Shvo, R. M. Laine, J. Chem.
Soc. Chem. Commun. 1980, 753 ± 754; d) B.-T. Khai, C. Concilio, G.
Porzi, J. Organomet. Chem. 1981, 208, 249 ± 251; e) B.-T. Khai, C.
Concilio, G. Porzi, J. Org. Chem. 1981, 46, 1759 ± 1760; f) A. Arcelli,
B.-T. Khai, G. Porzi, J. Organomet. Chem. 1982, 231, C31 ± C34; g) S.-I.
Murahashi, K. Kondo, T. Hakata, Tetrahedron Lett. 1982, 23, 229 ±
[
2
1
32; h) R. M. Laine, D. W. Thomas, L. W. Cary, J. Am. Chem. Soc.
982, 104, 1763 ± 1765; i) S.-I. Murahashi, N. Yoshimura, T. Tsumiya-
[11]
ethylene and stereoselective ring-opening metathesis poly-
merization of norbornene[ . Here we report a novel tantalum
initiator system and a new approach to generating catalyti-
cally active enolate species from monomer-coordinated com-
plexes. We prepared and characterized new half-metallocene
12]
ma, T. Kojima, J. Am. Chem. Soc. 1983, 105, 5002 ± 5011; j) C. W. Jung,
J. D. Fellmann, P. E. Garrou, Organometallics 1983, 2, 1042 ± 1044.
5] In a separate experiment, we confirmed that 1-(2-ethyl-3-methylqui-
nolin-6-yl)ethanone (0.20 mmol) reacted with tripropylamine
[
(
(
3
1.0 mmol) in the presence of RuCl
0.06 mmol) in dioxane (5 mL) at 1808C for 40 h to afford 1-(2-ethyl-
-methylquinolin-6-yl)pentan-1-one in 51% yield, and SnCl ´ 2H
proved to be unnecessary for the alkylation.
3 2 3
´ nH O (0.02 mmol) and PPh
complexes of tantalum with MMA and 1,4-diaza-1,3-buta-
diene (DAD)[
13, 14]
ligands, and the tantalum ± MMA com-
2
2
O
plexes, upon addition of one equivalent of AlMe , were found
3
[
[
6] For example, 1H NMR (400 MHz) analysis of the crude reaction
mixture of 1a and 2a, after usual workup prior to separation, showed
no signal for the methine proton of an a,a-dialkylated ketone.
to be catalysts for the polymerization of MMA.
Scheme 1 shows the preparation of tantalum ± MMA com-
5
7] Treatment of equimolar amounts of 1b and 2a under the usual
conditions gave 2-methyl-1-phenylhexan-1-one (3 f) in only 5% yield,
and the yield of 3 f was not improved at much longer reaction times.
8] M. Palucki, S. L. Buchwald, J. Am. Chem. Soc. 1997, 119, 11108 ±
plexes from [Cp*TaCl ] (1; Cp* ˆ h -C Me ). Reduction of 1
4
5
5
with sodium amalgam in toluene followed by addition of
MMA afforded the MMA complex [Cp*TaCl (h -supine-
4
2
[
[
MMA)] (2), which was alternatively prepared by treatment
1
1109.
III
[15]
9] J.-E. Bäckvall, R. L. Chowdhury, U. Karlsson, G. Wang in Perspectives
in Coordination Chemistry (Eds.: A. F. Williams, C. Floriani, A. E.
Merbach), VCH, New York, 1992, pp. 463 ± 486.
of the dinuclear Ta complex [{Cp*TaCl } ] (3) with MMA.
2 2
[
16]
The structure of 2 (Figure 1) is essentially the same as that
4
[17]
of [Cp*TaCl (h -supine-MA)].
Reaction of 2 with one
2
[
10] a) B. C. Hamann, J. F. Hartwig, J. Am. Chem. Soc. 1997, 119, 12382 ±
equivalent of the dilithium salt of 1,4-bis(p-methoxyphenyl)-
,4-diaza-1,3-butadiene (p-MeOC H -DAD) or the dilithium
1
1
1
2383; b) H. Muratake, A. Hayakawa, M. Natsume, Tetrahedron Lett.
997, 38, 7577 ± 7580; c) H. Muratake, M. Natsume, Tetrahedron Lett.
997, 38, 7581 ± 7582; d) J. Šhman, J. P. Wolfe, M. V. Troutman, M.
1
6
4
salt of 1,4-dicyclohexyl-1,4-diaza-1,3-butadiene (Cy-DAD) in
THF afforded the half-sandwich DAD complexes of tantalum
Palucki, S. L. Buchwald, J. Am. Chem. Soc. 1998, 120, 1918 ± 1919.
4
and 5, respectively. The 1H NMR spectra of 4 and 5
displayed two doublets at d ˆ 6.67 and 6.84 (J ˆ 3.4 Hz) for 4
[*] Prof. K. Mashima, Y. Matsuo, Prof. K. Tani
Department of Chemistry
Graduate School of Engineering Science
Osaka University
Toyonaka, Osaka 560-8531 (Japan)
Fax : (‡81)6-6850-6296
E-mail: mashima@chem.es.osaka-u.ac.jp
[
**] We thank Professor emeritus A. Nakamura (Osaka University) for
fruitful discussions. The present research was supported in part by a
grant-in-aid for Scientific Research on Priority Areas ªMolecular
Physical Chemistryº from the Ministry of Education, Science, Culture,
and Sports. Y.M. is a research fellow of the Japan Society for the
Promotion of Science, 1998 ± 2000.
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
960
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4005-0960 $ 17.50+.50/0
Angew. Chem. Int. Ed. 2001, 40, No. 5