Direct Synthesis of Ketones from Primary Alcohols and 1-Alkenes

Full text of DOI:10.1002/(SICI)1521-3773(19980202)37:1/2<145::AID-ANIE145>3.0.CO;2-0

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Direct Synthesis of Ketones from Primary
Alcohols and 1-Alkenes**
CH3
3a
4a
1a
PhCHO
N
N
C
Chul-Ho Jun,* Chan-Woo Huh, and Sang-Jin Na
–H2O
6
2a
H
Ph
Activation of the aldehydic carbon ±hydrogen bond by tran-
sition metal complexes has received much attention in organic
synthesis because of its potential to convert aldehydes into
ketones by hydroacylation.[1] Although intramolecular hydro-
acylation has been studied in detail,[2] only a few methods have
been reported for transition metal catalyzed intermolecular
hydroacylation.[3] Recently, we developed a direct chelation-
assisted intermolecular hydroacylation.[4] Primary and secondary
alcohols can be oxidized to aldehydes and ketones through
hydrogen transfer by a transition metal catalyst. In the course
of this oxidation, hydrogen atoms are transferred to hydrogen
acceptors such as ketones or alkenes to produce alcohols and
alkanes, respectively.[5,6] If oxidation by transition metal medi-
ated hydrogen transfer and hydroacylation occur consecu-
tively with the aid of identical catalysts and olefins, it should
be possible to prepare ketones directly from primary alcohols
and alkenes. We describe here a one-pot synthesis of a ketone
from a primary alcohol and a 1-alkene using a transition metal
catalyst together with 2-aminopyridine derivatives. To the
best of our knowledge, this is the first example of a direct
ketone synthesis from a primary alcohol and a 1-alkene.
Benzyl alcohol (1a) was treated with 1-pentene (2a) at
1308C for 72 h using as catalyst a mixture of [chlorotris(tri-
phenylphosphane)rhodium(i)] (3a, 10 mol% based upon 1a)
and 2-amino-3-picoline [4a, 100 mol%; Eq. (a)]. Hexano-
7
2a
3a
CH3
H2O
5a
N
N
–4a
C
Ph
8
Scheme 1. Mechanism for the direct synthesis of ketones from primary
alcohols and 1-alkenes by oxidation and hydroacylation.
7 and H2O. Formation of an aldimine from a primary alcohol
and a primary amine in the presence of a transition metal
catalyst is presumed to be the key step in N-alkylation of
primary amines with primary alcohols.[7] Subsequent hydro-
iminoacylation of 2a with 7 leads to ketimine 8, as reported
earlier.[8] Hydrolysis of 8 by H2O, formed through the reaction
of 4a with 6, affords ketone 5a as the final product. Direct
synthesis of 5a from 2a and 6 by chelation-assisted hydro-
acylation has already been reported.[4] Since 2a must serve
both as a hydrogen acceptor in the first step and as a
hydroacylation substrate in the second step, the amount of 2a
should be at least twice that of 1a.[9]
To determine the intermediates, p-methoxybenzyl alcohol
(1b) was allowed to react at 1308C for 72 h with allylbenzene
(9) under cocatalysis with 3a (10 mol%) and 4a (100 mol%).
This resulted in a mixture of p-methoxy-g-phenylbutanophe-
none (10), anisaldehyde (11), anisole (12), and propylbenzene
(13) in 63, 2, 8, and 61% yield, respectively, based upon 1b
[Eq. (b)].[10] Compound 13 is the hydrogenation product of 9,
10 mol% [Rh(PPh3)3Cl] 3a
PhCH2OH
+
100 mol% 2-amino-3-picoline 4a
2a
1a
130oC, 72 h
1
:
10
(a)
O
Ph
5a
74 %
10 mol% 3a
Ph
CH3O
CH2OH
+
2
100 mol% 4a
phenone (5a) was isolated in 74% yield after chromatogra-
phy. The reaction proceeded quite well without a solvent. A
possible mechanism for this one-pot synthesis of 5a from 1a
and 2a is illustrated in Scheme 1. The first step must be
oxidation by hydrogen transfer, in which primary alcohol 1a is
converted into aldehyde 6 via complex 3a. Hydrogen atoms
generated from 1a must be transferred to 2a to afford
pentane.[6] The aldehyde then reacts with 4a to form aldimine
130oC, 72 h
1b
9
O
C
Ph
CH3O
Ph
+
(b)
13 ( 61 %)
10 ( 63 %)
CH3O
+
CH3O
CHO
+
[*] Prof. Dr. C.-H. Jun, C.-W. Huh, S.-J. Na
Department of Chemistry
Yonsei University
Seoul 120-749 (Korea)
12 ( 8 %)
11 ( 2 %)
Fax: Int. code ‡ (82)2-364-7050
e-mail: junch@alchemy.yonsei.ac.kr
[**] This work was supported by the Korean Science and Engineering
Foundation (grant-in-aid 961-0306-054-2) and the Korean Ministry of
Education (project no. BSRI-96-3422). The authors wish also to thank
IBRD (the International Bank for Reconstruction and Development)
for the purchase of a 250-MHz NMR spectrometer.
while 11 is an oxidation product of 1b and 12 the decarbon-
ylation product of 11. Establishment of the presence of 11 and
13 confirms that hydrogen transfer occurs from the primary
alcohol to the 1-alkene.
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Table 2. Results of the hydroacylation of 1-pentene (2a) with benzyl
alcohol (1a) to give hexanophenone (5a) in the presence of RhCl3 ´ xH2O
and PPh3 as catalyst system, as well as various amines (100 mol%).[a]
In the catalytic reaction of 1a and 2b with RhCl3 ´ H2O (3b)
and PPh3 under the same reaction conditions as above,
heptanophenone (5b) was obtained in much higher yield
(84%) than in the reaction with 3a. The reason is not clear,
but the active catalyst 3a might be freshly generated in situ by
the reaction of 3b with PPh3.[11]
Entry
Amine
Yield[%][b]
1
54
To clarify the influence of 4a, this substance was introduced
in various concentrations into the hydroacylation of 2a with 4-
biphenylmethanol (1c). Reaction occurred at 1308C in the
course of 72 h with the catalytic system composed of 3b
(10 mol%) and PPh3 (Table 1). No ketone was obtained in the
absence of 4a, as expected. The yield of decarbonylation
product 15 decreased with increasing concentration of 4a.
This suggests that a high concentration of 4a retards the
decarbonylation of aldehyde generated from alcohol by
increasing the probability of carbon ± hydrogen bond cleavage
of carboxaldimine, which is present in higher concentration.
2
3
91
9
4
5
63
0
Table 1. Influence of the concentration of 2-amino-3-picoline (4a) on the
reaction of 4-biphenylmethanol (1c) with 1-pentene (2a).[a]
CH2OH
6
7
3
0
50 mol% PPh3
+
2a
10 mol% RhCl3 · xH2O 3b
4a, 130°C, 72 h
Ph
1c
1
: 10
O
CHO
C3H7
+
+
Biphenyl
[a] A mixture of 1a (0.48 mmol), 2a (4.8 mmol), 3b (0.048 mmol), PPh3
(0.24 mmol), and an amine (0.48 mmol) was heated for 40 h at 1308C.
[b] Isolated 5a.
Ph
Ph
5i
14
15
Entry 4a[mol%]
Yield(5i)[%]
5i[b]
14[b]
15[b]
1
2
3
4
20
50
100
200
21
55
67
88
55
86
92
9
4
0
0
36
10
8
Catalytic reactions of various primary alcohols and 1-
alkenes with 3b (3.3 mol% based upon alcohol) and PPh3
(16.5 mol%) as well as 4b (100 mol%) at 1308C for 12 h were
also examined (Table 3). The resulting hydroacylated ketones
100
0
[a] A mixture of 1c (0.48 mmol), 2a (4.8 mmol), 3b (0.048 mmol), PPh3
(0.24 mmol), and various amounts of 4a was heated for 72 h at 1308C.
[b] Relative amounts determined by gas chromatography.
O
Me
Various types of amine derivatives were examined with the
catalytic system consisting of 3b and PPh3 (Table 2). Among
2-aminopyridine derivatives, 2-amino-4-picoline (4b) showed
the greatest catalytic activity, and 2-amino-6-picoline (4c) the
least. This may be because of steric hindrance by the 6-methyl
group (see 16). The nitrogen atom in the pyridinyl group
would coordinate to the metallic center with difficulty in this
case, so that the metal and carbon ± hydrogen bonds in the
aldimine would not be brought into sufficiently close prox-
imity. 2-Aminomethylpyridine (4e) showed no catalytic
activity, perhaps due to the formation of a less-favored six-
membered ring metallacyclic complex such as 17, or to the
instability of the N-alkylaldimine compared with the more
conjugated N-arylaldimine. Even N,N-dimethylurea (4 f),
which lacks the 2-aminopyridine moiety, provided a hydro-
acylated product in 3% yield, possibly via intermediate 18.
This clearly demonstrates that formation of the five-mem-
bered metallacyclic intermediate is a prerequisite for this
reaction. No hydroacylated product was detected with
triethylamine (4g).
N
Me
N
N
CH3
N
N
L2
Rh
Rh
H
N
Rh
L2
L2
Ph
Cl
Ph
H
H
Cl
Cl
Ph
18
17
16
were linear, not branched systems.[12] There appear to be no
limitations with respect to the 1-alkene component. Even the
sterically hindered 1-alkene 3,3-dimethyl-1-butene (2d) pro-
vided 5d in fairly good yield (85%). All the benzylic alcohols
1a ± 1d provided good results, although yields with aliphatic
primary alcohols like 1e were low (22%).
We thus present a general synthesis for ketones starting
from 1-alkenes and primary alcohols with the catalytic
assistance of 2-aminopyridine derivatives and transition metal
complexes. This newly developed synthesis achieves the
generality required for a practical organic synthetic proce-
dure.
146
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COMMUNICATIONS
Table 3. Ligand-supported intermolecular hydroacylation of 1-alkenes 2 with primary alcohols 1.[a]
[1] a) J. Schwartz, J. B. Cannon, J. Am. Chem.
Soc. 1974, 96, 4721; b) C. F. Lochow, R. G.
Miller, ibid. 1976, 98, 1281; c) P. Isnard, B.
Denise, R. P. A. Sneeden, J. Organomet.
Chem. 1982, 240, 285.
O
R'
3.3 mol% 3b, 16.5 mol% PPh3
R
CH2OH
+
R
R'
100 mol% 4b, 130oC, 12h
1
2
5
1
:
10
[2] a) R. W. Barnhart, B. Bosnich, Organome-
tallics 1995, 14, 4343; b) R. W. Barnhart, X.
Wang, P. Noheda, S. H. Bergens, J. Whelan,
B. Bosnich, J. Am. Chem. Soc. 1994, 116,
1821; c) Y. Taura, M. Tanaka, K. Funakoshi,
K. Sakai, Tetrahedron Lett. 1989, 30, 6349; d)
D. P. Fairlie, B. Bosnich, Organometallics
1988, 7, 946; e) D. P. Fairlie, B. Bosnich, ibid.
1988, 7, 936; f) B. R. James, C. G. Young, J.
Chem. Soc. Chem. Commun. 1983, 1215; g)
D. Milstein, ibid. 1982, 1357; h) R. C. Larock,
K. Oertle, G. F. Potter, J. Am. Chem. Soc.
1980, 102, 190; i) R. E. Campbell, Jr., C. F.
Lochow, R. G. Miller, ibid. 1980, 102, 5824; j)
K. Sakai, J. Ide, O. Oda, N. Nakamura,
Tetrahedron Lett. 1972, 13, 1287.
[3] a) T. Kondo, M. Akazome, Y. Tsuji, Y.
Watanabe, J. Org. Chem. 1990, 55, 1286; b)
Y. Tsuji, S. Yoshii, T. Ohsumi, T. Kondo, Y.
Watanabe, J. Organomet. Chem. 1987, 331,
379; c) T. B. Marder, D. C. Roe, D. Milstein,
Organometallics 1988, 7, 1451; d) K. P. Vora,
C. F. Lochow, R. G. Miller, J. Organomet.
Chem. 1980, 192, 257.
Alcohol
Entry R (1)
1-Alkene
R' (2)
Hydroacylated
product 5
Yield[%][b]
1
Ph (1a)
n-C3H7 (2a)
5a
86
2
3
4
Ph (1a)
Ph (1a)
Ph (1a)
n-C4H9 (2b)
n-C8H17 (2c)
5b
5c
84
66
t-C4H9 (2d)
H (2e)
5d
5e
85
43
5[c] Ph (1a)
6
Ph (1a)
Cyclohexyl (2 f)
C6F5 (2g)
5 f
5g
76
69
[4] C.-H. Jun, H. Lee, J.-B. Hong, J. Org. Chem.
1997, 62, 1200.
7[d] Ph (1a)
[5] a) R. Noyori, S. Hashiguichi, Acc. Chem.
Res. 1997, 30, 97; b) G. Zassinovich, G.
Mestroni, Chem. Rev. 1992, 92, 1051; c)
R. A. W. Johnstone, A. H. Wilby, ibid. 1985,
85, 129; d) G. Brieger, T. J. Nestrick, ibid.
1974, 74, 567.
8
4-MeOC6H4 (1b) n-C3H7 (2a)
5h
77
[6] R. Spogliarich, A. Tencich, J. Kaspar, M.
Graziani, J. Organomet. Chem. 1982, 453.
[7] a) Y. Watanabe, Y. Morisaki, T. Kondo, T.
Mitsudo, J. Org. Chem. 1996, 61, 4214; b) S. I.
Murahashi, K. Kondo, T. Hakada, Tetrahe-
dron Lett. 1982, 23, 229.
[8] a) J. W. Suggs, J. Am. Chem. Soc. 1979, 101,
489; b) C.-H. Jun, J.-S. Han, J.-B. Kang, S.-I.
Kim, J. Organomet. Chem. 1994, 474, 183; c)
C.-H. Jun, J.-B. Kang, J.-Y. Kim, ibid. 1993,
458, 193; d) Tetrahedron Lett. 1993, 34,
6431.
[9] By increasing the ratio of 1a to 2a from 1:1
to 1:2, 1:5, and 1:10, the yield of 5a was also
increased by 44, 68, and 74%, respectively.
We therefore chose a ratio of 1:10 for the
concentrations of 1a to 2a.
9
4-PhC6H4 (1c)
2-Naphthyl (1d)
PhCH2CH2 (1e)
n-C3H7 (2a)
n-C3H7 (2a)
n-C3H7 (2a)
5i
84
10
11
5j
5k
78
22[e]
[a] A mixture of 1 (1.435 mmol), 4b (1.435 mmol), 3b (0.048 mmol), PPh3 (0.239 mmol), and 2
(14.300 mmol) was heated for 12 h at 1308C. [b] Yield of hydroacylated product isolated by column
chromatography (SiO2, hexane/EtOAc, 5/2). [c] Benzene was used as solvent. [d] Toluene
(200 mg) was added as a solvent. [e] With 3a as catalyst. Use of the same molar quantity of 3b and
PPh3 instead of 3a led to the isolation of 5k (10%).
Experimental Section
[10] The yield of 10 is calculated on the basis of hydrogen atoms released
from 1b.
[11] J. A. Osborn, G. Wilkinson, Inorg. Syn. 1967, 10, 67.
[12] Under these reaction conditions, no decarbonylation product was
detected from 1b ± e.
In a typical experiment, a mixture of 1a (155 mg, 1.44 mmol), 4b (155 mg,
1.44 mmol), and PPh3 (62.6 mg, 0.239 mmol) was dissolved in 2a (1000 mg,
14.3 mmol) in a 2.5-mL screw-capped vial. After the mixture had been
stirred for several minutes, complex 3b (10.0 mg, 0.048 mmol) was added,
and the resulting mixture was stirred for 12 h at 1308C. The solution was
concentrated, and the residue obtained was purified by column chroma-
tography (hexane/EtOAc, 5/2) to give 218 mg of 5a (86% yield).
Received: July 2, 1997 [Z10629IE]
German version: Angew. Chem. 1998, 110, 150 ± 152
Keywords: C ± H activation
´ homogeneous catalysis ´
hydroacylations ´ hydrogen transfer ´ metallacycles
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