Solvent-free chelation-assisted catalytic C-C bond cleavage of unstrained ketone by rhodium(I) complexes under microwave irradiation

Article abstract of DOI:10.1002/adsc.200505233

A highly efficient C-C bond cleavage of unstrained aliphatic ketones bearing β-hydrogens with olefins was achieved using a chelation-assisted catalytic system consisting of (Ph₃P)₃RhCl and 2-amino-3-picoline by microwave irradiation under solvent-free conditions. The addition of cyclohexylamine catalyst accelerated the reaction rate dramatically under microwave irradiation compared with the classical heating method.

Full text of DOI:10.1002/adsc.200505233

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DOI: 10.1002/adsc.200505233
ꢀ
Solvent-Free Chelation-Assisted Catalytic C C Bond Cleavage of
Unstrained Ketone by Rhodium(I) Complexes under Microwave
Irradiation
a
a
a
a
b
´
Jeong-Ae Ahn, Duck-Ho Chang, Young Jun Park, Ye Rim Yon, Andre Loupy,
Chul-Ho Juna,*
a
Center for Bioactive Molecular Hybrid (CBMH) and Department of Chemistry, Yonsei University, Seoul 120-749, South
Korea
Fax: (þ82)-2-3147-2644; e-mail: junch@yonsei.ac.kr
b
´
´
ˆ
´
Laboratoire des Reactions Selectives sur Supports, ICMMO, CNRS UMR 8615, batiment 410, Universite Paris-Sud,
91405 Orsay Cedex, France
Received: June 3, 2005; Accepted: October 13, 2005
Supporting Information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
ꢀ
Abstract: A highly efficient C C bond cleavage of
unstrained aliphatic ketones bearing b-hydrogens
with olefins was achieved using a chelation-assisted
catalytic system consisting of(Ph P)3RhCl and 2-
3
amino-3-picoline by microwave irradiation under
solvent-free conditions. The addition of cyclohexyla-
mine catalyst accelerated the reaction rate dramati-
cally under microwave irradiation compared with
ð1Þ
When the reaction ofbenzylacetone ( 1a, 1 mmol) and
the classical heating method.
norbonylene (2a, 1.2 mmol) was carried out using the
ꢀ
Keywords: C C bond cleavage; chelation-assistance;
microwave heating; Rh(I) complex; solvent-free re-
action
cocatalyst system of(PPh )3RhCl (3, 5 mol %) and 2-
3
amino-3-picoline (4, 20 mol %) at 2008C for 5 min under
MWirradiation[7] in closed vessels (due to the rather low
boiling point ofthe alkene), a 44% yield of2-acetylnor-
bonane (6a)[8] was obtained along with a 40% yield of
styrene, as determined by GC. When the reaction was
performed at 2008C under conventional heating (D) in-
ꢀ
C C bond activation is ofcurrent interest to organome-
tallic chemists.[1] However, there have been very few ex- side a thermostatted oil bath, only a 9% yield of 6a was
ꢀ
amples ofcatalytic C C bond activation in spite ofits
obtained after the same reaction time with similar ramps
usefulness in organic synthesis.[2,3] The substrates are in temperatures (Table 1, entries 1 and 2).
confined mainly to ring-strained molecules and specially
designed model compounds. In the course ofour studies
The reaction is believed to proceed not through direct
C C bond cleavage ofketone 1a by Rh(I) complex 3. In-
ꢀ
on hydroacylation using 2-amino-3-picoline as a tempo- stead, a ketimine intermediate 8a is initially formed in
rary chelating auxiliary,[4] we found a C C bond activa- situ from ketone 1a and 2-amino-3-picoline (4) with
ꢀ
ꢀ
tion ofan unstrained ketone utilizing a chelation-assist-
elimination ofH 2O. Chelation-assisted C C bond cleav-
ed protocol.[5] Forexample, ketone 1reacted with alkene age of 8a by Rh(I) with 2a produces ketimine 9a and al-
2 under the cocatalyst system of(PPh 3)3RhCl (3) and 2- kene 7a (Scheme 1). Subsequent hydrolysis of 9a with
amino-3-picoline (4) to give an alkyl group-exchanged H2O, previously formed by condensation of 1a and 4,
ketone 5 and alkene 6 [Eq. (1)].[5a]
Because this chelation-assisted C C bond cleavage is egy was previously applied to hydroacylation reactions
too sluggish, high temperature and long reaction times in which aldehydes and alkenes were transformed into
were required to continue the reaction. Therefore, we ketones.[9]
leads to ketone 6a. This type ofchelation-assisted strat-
ꢀ
were intrigued to use a solvent-free microwave (MW)-
The beneficial result of MW irradiation compared
accelerated reaction since this method allows easy ac- with conventional heating can be explained as follows.
cess to high temperatures.[6]
In the chelation-assisted catalytic C C bond activation,
ꢀ
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ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
55

Jeong-Ae Ahn et al.
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Scheme 2. Increase ofthe polarity ofthe system during the
progress ofthe reaction from the ground state (GS) towards
the transition state (TS).
20 mol %), the yield of 6a was increased from 9% to
16% under conventional thermal reaction conditions
(Table 1, entries 1 and 3) whereas it increased from
44% to 85% under MWirradiation (entries 2 and 4). Ad-
dition ofcyclohexylamine ( 5a) might lower the enthalpy
ofactivation from ketone and 2-amino-3-picoline to the
corresponding ketimine 8a by generating an intermedi-
ate ketimine 12. This type ofrate enhancement was also
developed in chelation-assisted hydroacylation using a
transimination protocol.[10] In this case, two transition
ꢀ
Scheme 1. Mechanism ofchelation-assisted C C bond activa-
tion of 1a with norbonylene (2a).
the rate-determining step is supposed to be the conden- states are involved as the reaction progresses from the
sation (imine formation) between ketone 1a and 2-ami- ground state (GS) to the intermediate 8a. The polarities
no-3-picoline (4). As shown previously for hydroacyla- ofthese two transition states, TS1 ( 11) and TS2 (13)
tion, MWirradiation accelerates the condensation ofke-
(Scheme 3), are increased when compared with those
tone and 2-amino-3-picoline when compared with clas- ofstarting materials, 1 and 2a, or intermediate 12. More-
sical heating by lowering the energy level ofthe polar
transition state 10 as the polarity ofthe system is in-
creased during the progress ofthe reaction rfom the
ground state (GS) towards the transition state (TS)
over, increasing the polarity ofthe transition state TS1
or TS2 might lower the enthalpy ofactivation by MW ir-
radiation.
Among the primary amines tested, cyclohexylamine
(Scheme 2). It has been reported that the more polar (5a) reveals a better reactivity than aniline (5b) (Table 2,
transition state is better stabilized by dipole-dipole elec- entries 2 and 3). The reason must be that the more nucle-
trostatic interactions ofMW, resulting in a lowering of
ophilic (basic) the amine is, the more polar are the tran-
sition states (TS1 or TS2) developed. Another possible
hypothesis is that CyNH2 could act as a base to abstract
the enthalpy ofactivation. [6a, b]
The rate ofthe overall reaction can be enhanced by
the addition ofcyclohexylamine. In its presence ( 5a, a proton in 4 thereby generating an amide anion 14 more
ꢀ
Table 1. Rh(I)-catalyzed C C bond activation of 1a with norbonylene (2a).
Entry
Cy-NH2
Activation mode
Yield[a] of 6a (7a)
1
2
3
4
none
none
20 mol %
20 mol %
D
MW
D
9% (8%)
44% (40%)
16% (14%)
85% (84%)
MW
[a]
Yield was determined by GC and the ratio of exo/endo-6a was ca. 7/3.
56
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Adv. Synth. Catal. 2006, 348, 55 – 58

ꢀ
Catalytic C C Bond Cleavage ofUnstrained Ketone by Rhodium(I) Complexes
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Figure 1. Yield of 6a from 1a and 2a depending on reaction
time at 2008C with catalysts 3 (5 mol %), 4 (20 mol %) and
5 (20 mol %) under MW irradiation.
The reactions of 1a and 2a were completed within
10 min (Figure 1). This can be explained considering
that the strain energy ofnorbonylene ( 2a) is partially re-
lieved by forming a less strained 2-acetylnorbonane (6a),
whichmightbeadrivingforceinthisreaction. Theforma-
tion ofstyrene is another driving force in this transforma-
Scheme 3. Increase ofthe polarity system during the progress
ofthe reaction from the ground state (GS) towards the tran-
sition state (TS).
susceptible to the formation of ketimine 8a than 4 tion since the relatively stable, conjugated styrene is gen-
[Eq. (2)].
erated from the non-conjugated norbonylene.
Other aliphatic ketones bearing b-hydrogens were ap-
ꢀ
plied in this reaction, and fairly good yields of C C bond
cleaved products were obtained in 30 min (Table 3, en-
tries 2 and 3). Since the reactions with unstrained olefins
like vinylcyclohexane or 1-alkene were sluggish, harsher
reaction conditions were required to get moderate
ð2Þ
ꢀ
yields ofC C bond cleaved products (entries 4–7)
To test this hypothesis, secondary and tertiary amines such as, for example, a high concentration (100 mol %)
such as 5c–5e, which could not form intermediate ke- of2-amino-3-picoline and additional benzoic acid
times 12 but are stronger bases than CyNH2, were ap- (10 mol %). The reason must be that with an unstrained
plied in this reaction (entries 4–6). No enhanced reac- olefin there is no energy gain for relieving the strain en-
tivity was found with these amines. This result indicates ergy, unlike with norbonylene. Therefore, a large excess
that the enhanced reactivity ofcyclohexylamine might
(7 equivs.) ofolefin was used to drive the forward reac-
be related to the other reaction pathways such as the tion.
transimination as shown in Scheme 3, not simply to the
basicity, although the exact reason is not clear at the aliphatic ketones bearing b-hydrogens were achieved
ꢀ
In conclusion, highly efficient C C bond cleavages of
present stage.
with olefins using a chelation-assisted catalytic system
consisting of(Ph P)3RhCl and 2-amino-3-picoline by
3
MW irradiation under solvent-free conditions. Addi-
tional cyclohexylamine catalyst accelerated the reaction
rate dramatically, and the rate enhancement was ob-
served under MW irradiation compared with classical
heating probably due to a specific non-purely thermal
MW effect.
ꢀ
Table 2. Rh(I)-catalyzed C C bond activation of 1a with ad-
ditional amine.
Experimental Section
Entry
Amine (5)
pKa
Yield[a] of 6a (7a)
ꢀ
1
2
3
4
5
6
7
none
Cy-NH2 (5a)
Ph-NH2 (5b)
Diethylamine (5c)
Dibutylamine (5d)
Triethylamine (5e)
Pyridine (5f)
–
10.7
4.6
11.0
11.3
10.8
5.3
42% (38%)
83% (80%)
36% (32%)
44% (35%)
30% (25%)
27% (19%)
16% (20%)
Typical Procedure for the Catalytic C C Bond
Cleavage of Ketone by Wilkinsonꢀs Complex under
Microwave Irradiation
In a 10-mL thick-wall Pyrex tube, were introduced successively
benzylacetone (1a, 148 mg, 1 mmol), 2-amino-3-picoline (4,
21.6 mg, 0.2 mmol), norbonylene (2a, 112.8 mg, 1.2 mmol),
and (Ph3P)3RhCl (3, 46.3 mg, 0.05 mmol). The reaction vessel
was capped with a Teflon septum and installed in the CEM mi-
[a]
Yield was determined by GC.
Adv. Synth. Catal. 2006, 348, 55 – 58
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57

Jeong-Ae Ahn et al.
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ꢀ
Table 3. Rh(I)-catalyzed C C bond activation ofvarious ketones with
several alkenes.
References and Notes
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[a]
GC yield based on 1 and values in parenthesis are isolated yields.
The ratio was determined by H NMR.
[b]
[c]
1
7 equivs. ofoleifn were used under 100 mol %
10 mol% benzoic acid.
4, 15 mol % 5, and
crowavereactor. Thereactionwascarriedoutwithinternalmag-
netic stirring for 5 min to ensure homogeneous conditions at
2008C under microwave irradiation. After cooling, the reaction
mixture was filteredthrough a short column filled withsilicaand
washed with CH2Cl2 and ethyl acetate. The filtrate was analyzed
by GC and GCD, and determined as 44% of2-acetylnorbonane
(6a, exo- and endo-mixtures) and 40% ofstyrene ( 7a). A ratio of
exo- and endo-2-acetylnorbonanes was determined by 1H NMR
spectroscopy. 2-Acetylnorbonane comprised an exo and endo-
mixtures in a ca. 72/28 ratio. When the reaction was carried
out with additional cyclohexylamine (5a, 20 mol % based on
1a), 85% of 6a and 84% of 7a were determined.
Ed. 2004, 43, 6250.
[7] The MW reaction was performed using a CEM Discover
monomode reactor with measurement and monitoring of
temperature by IR detection and power modulation be-
tween 15–300 W.
[8] Since 2-acetylnorbonane (6a) is volatile, isolated yields
were not accurate, and yields were determined by GC.
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Acknowledgements
This work was supported by grant No. R01-2005-000-10548-0
from the Basic Research Program of the Korea Science & Engi-
neering Foundation.
58
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Adv. Synth. Catal. 2006, 348, 55 – 58