One-pot catalytic C-C double bond cleavage of α,β-enones aided by alkyl group-immobilized silica spheres

Article abstract of DOI:10.1016/j.tetlet.2009.10.103

Catalytic C-C double bond cleavage of α,β-enones with a 1-alkene and H₂O was carried out in the presence of a (Ph₃P)₃RhCl catalyst, 2-amino-3-picoline, cyclohexylamine, benzoic acid, and alkyl group-immobilized silica spheres. Upon completion of the reaction, the corresponding ketones were obtained without needing a further hydrolysis step. In this reaction, alkyl group-immobilized silica spheres act as a water reservoir for hydrolysis of an intermediate ketimine and as a phase divider between the organic solution and H₂O.

Full text of DOI:10.1016/j.tetlet.2009.10.103

Tetrahedron Letters 51 (2010) 160–163
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
One-pot catalytic C–C double bond cleavage of a,b-enones aided by alkyl
group-immobilized silica spheres
*
Dong Hun Lee, Eun-Ae Jo, Jung-Woo Park, Chul-Ho Jun
Department of Chemistry and Center for Bioactive Molecular Hybrid, Yonsei University, Seoul 120-749, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Catalytic C–C double bond cleavage of a,b-enones with a 1-alkene and H2O was carried out in the pres-
Received 17 September 2009
Revised 22 October 2009
Accepted 22 October 2009
Available online 27 October 2009
ence of a (Ph3P)3RhCl catalyst, 2-amino-3-picoline, cyclohexylamine, benzoic acid, and alkyl group-
immobilized silica spheres. Upon completion of the reaction, the corresponding ketones were obtained
without needing a further hydrolysis step. In this reaction, alkyl group-immobilized silica spheres act
as a water reservoir for hydrolysis of an intermediate ketimine and as a phase divider between the
organic solution and H2O.
This Letter is dedicated to the memory of
the late Professor Chi Sun Han (1926–2009)
of Yonsei University
Ó 2009 Elsevier Ltd. All rights reserved.
C–H bond activation by transition-metal catalysts is of current
interest in organic synthesis in terms of atom economy.1 We have
successfully developed a Rh(I)-catalyzed C–H bond activation
using 2-aminopyridine derivatives or benzylamine as a chelating
auxiliary to induce facile cyclometallation.2 In the course of our
studies on chelation-assisted C–H bond activation, the Rh(I)-cata-
lyzed hydroiminoacylation of an alkyne with an allylamine or an
aldehyde, followed by retro-Mannich type fragmentation of the
the aldimine survives even in the presence of H2O during the reac-
tion. Therefore, the aldimine B undergoes hydroiminoacylation
with 1-alkene (3a) mediated by the cocatalyst system of
(Ph3P)3RhCl (4) and 2-amino-3-picoline (5) to afford ketimine 7.
This type of transimination/hydroiminoacylation protocol has been
utilized in the efficient conversion of aldimine to ketimine.6 Now
the ketimine 7 is readily hydrolyzed by additional H2O giving ke-
tone 9a with regeneration of cyclohexylamine (2), which can be in-
volved in the catalytic cycle. Based on this it can be said that
without additional H2O no catalytic reaction takes place since
cyclohexylamine cannot be regenerated.
resulting
a
,b-unsaturated ketimine was found.3,4 We have also
,b-enone using amine
developed a C–C double bond cleavage of
a
and acid to produce ketones after hydrolysis step.5 For example,
the reaction of 4-phenyl-but-3-en-2-one (1a), 3,3-dimethyl-1-bu-
tene (3a), and cyclohexylamine (2, 200 mol % based upon 1a) was
carried out at 130 °C for 4 h in the presence of the catalyst system
of (Ph3P)3RhCl (4), 2-amino-3-picoline (5), and benzoic acid (6) to
give acetone and ketimine 7, which was hydrolyzed separately by
acidic H2O giving the corresponding ketone 9a in a 49% isolated
yield (Scheme 1a). This reaction requires greater than 100 mol %
However, addition of H2O afforded a very low yield of 9a (33%
isolated yield, Scheme 1b) from the reaction of 1a with 3a and
O
Cy
Ph
C
N
C
Ph
Me
(1a)
(Ph3P)3RhCl (4, 5 mol%)
t
-C4H9
of cyclohexylamine based on the starting
a,b-enone, and a further
5
2-amino-3-picoline ( , 20 mol%)
+
7
O
C
benzoic acid (6, 15 mol%)
toluene, 130 ºC, 4 h
Cy-NH2 (2, 2 eq)
hydrolysis step for the resulting ketimine 7 to liberate ketone (9a).
To decrease the amount of 2 used and to eliminate the separate
hydrolysis step, H2O can be added as a reactant to hydrolyze the
in situ generated ketimine 7 resulting in the formation of 9a di-
rectly (Scheme 1b). A proposed mechanism for this one-pot reac-
tion is depicted in Scheme 2. Cyclohexylamine 2 undergoes
+
t
(a)
+
Me
-C4H9
Me
O
8
3a
, 5 eq)
(
H+
H2O
C
Ph
t
-C4H9
9a
(
)
49 % isolated yield
conjugate addition to the
a,b-enone 1a, and the subsequent ret-
4
5
ro-Mannich type fragmentation of the resulting b-aminoketone A
generates a mixture of aldimine B and ketone 8. Since aldimine
is not much susceptible for hydrolysis compared with ketimine,
(3 mol%), (20 mol%)
1a + 3a
6
(5 eq)
(15 mol%)
2
Cy-NH2 ( , 50 mol%)
(b)
9a
33 % isolated yield
+
H2O (1 eq)
toluene, 130 ºC, 4 h
Scheme 1. (a) Retro-Mannich fragmentation and subsequent hydroacylation of 1a
with 3a, and 2 equiv of 2 in the presence of 4–6. (b) Reactions of 1a with 3a, a
catalytic amount of 2, and H2O in the presence of 4–6.
* Corresponding author. Tel.: +82 2 2123 2644; fax: +82 2 3147 2644.
E-mail address: junch@yonsei.ac.kr (C.-H. Jun).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.10.103

D. H. Lee et al. / Tetrahedron Letters 51 (2010) 160–163
161
O
Si OH
O
Si
O
O
O
C
Cy NH2
(2)
O
C
Ph
Me
Ph
t-C4H9
Si O
O
9a
(
)
(1a)
silica ball
Sc(OTf)3
(5 mol%)
OH
µ
Si
n-C15H31
(10 m)
(a)
separate
hydrolysis step
Si
O
O
H2O
+
11a
MeCN/MC
rt, 12 h
(0.40 mmol g-1
)
H2O
Cy
H
Cy
O
N
N
n-C18H37
Si
n-C15H31
10a
C
C
Ph
Me
Ph
t-C4H9
A
O
C
7
8
Me
Cy
Me
+
t-C4H9
retro-Mannich
fragmentation
O
C
3a
(
)
n-C18H37
11a
, 100 mg)
N
B
O
C
(1a)
Ph
4
(Ph3P)3RhCl ( )
2-amino-3-picoline (5)
(
Ph
9a
t-C4H9
C
Ph
H
4
(3 mol%)
(30 mol%)
(15 mol%)
Me
, 92 % isolated yield
5
+
4 hours
after the reaction for
O
6
2
(b)
Scheme 2. Proposed mechanism for retro-Mannich fragmentation and subsequent
hydroacylation of 1a with 3a and H2O in the presence of 2, 4–6.
t-C4H
9 (3a)
50 mol%
)
(
8
+
+
toluene, 130 ºC
C
H2O (1 eq)
Me
Me
H2O (100 mol %) in the presence of 2 (50 mol %), 4 (3 mol %), 5
(20 mol %), and 6 (15 mol %).7 To overcome this problem, it is nec-
essary to separate the H2O and organic solution phase ( Fig. 1).
Herein, we wish to report the efficient one-pot amine-assisted C–
Scheme 3. (a) Preparation of 11a through the immobilization reaction of 10a onto
silica spheres under Sc(OTf)3 catalysis. (b) Representative reaction of 1a with 3a and
H2O in the presence of 2, 4–6, and 11a.
C double bond cleavage of a,b-enones aided by alkyl group-immo-
Table 1
bilized silica spheres. Since the alkyl group-immobilized silica
spheres act as both a phase separator and a reservoir for water,
the activity of the transition-metal catalyst is maintained even in
the presence of water, and a separate hydrolysis step is avoided.
Recently, some organometallic catalytic reactions in aqueous
phase have been studied based on the heterogeneous system.8 We
have developed a new method for the surface-fabrication of the high
density long chain alkyl group-grafted silica, which can be used as a
divider between the organic reaction media and H2O absorbed on
the silica.9 Using this protocol, octadecyl group-functionalized silica
The effect of 2 on the catalytic C–C double bond cleavage of
subsequent hydroacylation with 3
a,b-enone (1) and
1a
3a
(0.2 mmol)
+
4
5
(3 mol%), (30 mol%)
2
6
(50 mol%), (15 mol%)
11 (100 mg)
(1.0 mmol)
9a
+
toluene, 130 ºC, 4 h
H2O (0.2 mmol)
Entry
1
Jctadecyl group-immobilized silica (11)
Isolated yield of 9a (%)
O
spheres 11a (loading rate of octadecyl group = 0.40 mmol gÀ1 10
were prepared by the reaction of silanol group on the surface of silica
ball (10 m in diameter, 11.67 nm pore size, purchased from Kroma-
)
Si
O
Si
O
O
O
Si
n
-C15H31
92
l
O
-1
sil) with octadecyltrimethallylsilane (10a) in the presence of a
Sc(OTf)3 catalyst (OTf = trifluoromethylsulfonate) at room tempera-
ture (Scheme 3a). To prove the effect of 11a, the catalytic reaction of
1a, 3a, and H2O (100 mol %) with the catalyst system of (Ph3P)3RhCl
(4), 2-amino-3-picolone (5), cyclohexylamine (2), and benzoic acid
(6) was carried out in the presence of 11a for 4 h to give the corre-
sponding ketone 9a in a 92% isolated yield without any further
hydrolysis step.11
11a,
(
0.45 mmol g )
Si
O
Si
O
O
O
Si
n-C15H31
11b,
2
3
49
28
Me
O
-1
(
0.71 mmol g )
Me
Si O Si
n
-C15H31
For comparison, other alkyl group-immobilized silica spheres
with different alkyl group loading rates were applied to this reac-
tion under the identical reaction conditions: reaction of 1a with 3a
at 130 °C for 4 h affording 9a (Table 1). Among these modified sil-
ica additives, 11a (loading rate of 0.45 mmol gÀ1) exhibited better
reactivity than 11b (0.71 mmol gÀ1), and 11c (1.06 mmol gÀ1), pre-
pared from octadecylmethyl-dimethallylsilane (10b) and octa-
decyldimethylmethallyl-silane (10c), respectively (entries 2 and
3). Interestingly, when the reaction of 1a with 3a was conducted
O
Me
(11c, 1.06 mmol g-1
)
O
Si O SiMe3
O
Si O
4
20
O
Si
n-C15H31
Si O
a
11a-SiMe
(
)
3
O
O
Si O SiMe3
5
6
30
49
O
silica sphere
(TMS-coated, 1.3 mmol g-1 a
Silica sphere (bare)
2
Cy NH2 ( )
)
Cy
Ph
N
C
+
O
C
a 11a–SiMe3 and TMS-coated silica spheres were prepared by the reaction of 11a or
untreated silica spheres with 1,1,1,3,3,3-hexamethyldisilazane, respectively.
t
-C4H9
Ph
t-C4H9
7
(9a)
2
i) Facile regeneration of
ii) Separation of H2O and
organic solution phase
using 11a–SiMe3, in which the residual silanol groups on 11a were
fully capped with trimethylsilyl groups by treatment of 11a with
1,1,1,3,3,3-hexamethyldisilazane,12 compound 9a was obtained in
a low isolated yield (20%) (entry 4), which suggests that the resid-
ual silanol groups on 11a are essential for the in situ hydrolysis
H2O
Figure 1. Hydrolysis of ketimine on the alkyl group-immobilized silica spheres.

162
D. H. Lee et al. / Tetrahedron Letters 51 (2010) 160–163
Table 2
Catalytic C–C double bond cleavage of a,b-enone (1) and subsequent hydroacylation with 3
O
C
(Ph3P)3RhCl (4, 3 mol%)
R1
1,
R2
5
2-amino-3-picoline ( , 30 mol%)
(
0.2 mmol)
2
cyclohexylamine ( , 50 mol%)
+
O
C
benzoic acid (6,15 mol%)
R3
R1
R3
toluene, 130 ºC
(3, 1.0 mmol)
(9)
+
n-C18H37
H2O (0.2 mmol)
(11a, 100 mg)
Entry
a
,b-Unsaturated ketone (1) (R1, R2)
Olefin (3) (R3)
Rxn time
4 h
Yield of 9a (%)
Yield of 9 without using 11aa (%)
1
2
3
4
5
6
7
8
Ph, Me (1a)
n-C4H9 (3b)
n-C6H13 (3c)
c-C6H12 (3d)
C6H5 (3e)
SiMe3 (3f)
SiEt3 (3g)
3a
89(98) (9b)
85(98) (9c)
77(80) (9d)
83(95) (9e)
89(99) (9f)
88(97) (9g)
(82) (9h)
41(51)
47(56)
25(33)
54(58)
30(45)
17(33)
(44)
Me, Me (1b)
Ph, Ph (1c)
45 min
14 h
3a
85(89) (9a)
51(61)
a
Isolated yield. The yields in parentheses are determined by GC.
step. Although the reason for this result is not clear, but we spec-
ulate that H2O bound on the surface of silanol groups readily inter-
acts with ketimine 7 to be hydrolyzed in organic solution as shown
in Figure 1. However, if silanol group on the silica surface is com-
pletely covered with hydrophobic SiMe3 or octadecylmethylsilyl
groups, there is no room for H2O on the silica surface, and H2O
may smear into the interior of the silica network. This fact was also
confirmed by the use of exclusive TMS-coated silica spheres (load-
ing rate: 1.3 mmol gÀ1), prepared by treatment of silica spheres
with 1,1,1,3,3,3-hexamethyldisilazane. With this TMS-coated silica
spheres, only a 30% yield of 9a was isolated (entry 5). When silica
spheres untreated with alkylating reagents were used, only a 49%
isolated yield of 9a was obtained (entry 6). It is known that transi-
tion-metal phosphine complexes can react with silanol groups on
the silica surface to generate inactive metal catalysts due to the
formation of P(V) species of the ligand phosphine.13
reaction alkyl group-immobilized silica spheres act as a water res-
ervoir for hydrolysis of the ketimine and a phase divider for the or-
ganic solution and H2O on the silica. This one-pot catalytic reaction
system is simple and efficient, and practical. Further applications of
this one-pot catalytic system with functional group-immobilized
silica are currently being investigated.
Acknowledgments
This work was supported by a Korea Research Foundation Grant
funded by the Korean Government (MOEHRD) (KRF-2008-313-
C00483), the WCU (World Class University) program through the
Korea Science and Engineering Foundation funded by the Ministry
of Education, Science and Technology (R32-2008-000-10217-0)
and the CBMH. D.H.L. and J.W.P. acknowledge the fellowships from
the BK21 program of the Ministry of Education and Human Re-
sources Development.
The reactions of various a,b-enones (1) with olefins (3) are sum-
marized in Table 2. The reaction of 4-phenyl-but-3-en-2-one (1a), 1-
hexene(3b), andH2Owascarriedoutat130 °C for4 hinthepresence
of 4 (3 mol %), 5 (30 mol %), 2 (50 mol %), and 6 (15 mol %) using the
octadecyl group-immobilized silica spheres (11a) to afford 1-phe-
nylheptan-1-one (9b) in an 89% isolated yield. Under identical reac-
tion conditions without 11a, the reaction of 1a and 3b produced a
41% isolated yield of 9b (Table 2, entry 1). Similar results were ob-
served in thereactionsof other 1-alkenes (3c–g), asfairly good yields
ofthecorrespondingisolatedketones(9c–g)wereobtainedwith11a
(Table 2, entries 2–6); only low yields of the products were obtained
in the absence of C18-immobilized silica 11a. When other substi-
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(3.6 mg, 0.2 mmol), (Ph3P)3RhCl (4, 5.5 mg, 0.006 mmol), 2-amino-3-picoline
(5, 6.5 mg, 0.06 mmol), cyclohexylamine (2, 9.9 mg, 0.1 mmol), and 11a
(100 mg) dissolved in 400 mg of toluene, then the reaction mixture was
stirred at 130 °C for 4 h. After the reaction, a crude mixture was purified by
column chromatography (SiO2, n-hexane/ethyl acetate = 20:1) to give 43.7 mg
(92% yield based on 1a) of 4,4-dimethyl-1-phenylpentan-1-one (9a).
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