Tandem catalytic triple-bond cleavage of alkyne in association with aldehyde, alkene, and water

Article abstract of DOI:10.1055/s-0029-1218000

In this tandem reaction the carbon-carbon triple bond of an alkyne is catalytically cleaved in association with aldehyde, al-kene, and H²O under catalyst mixtures of Rh(I), 2-amino-3-picoline, primary amine, and acid. The reaction starts with chelation-assisted hydroacylation of the alkyne with an aldehyde. The retro-Mannich-type fragmentation of the resulting ,α,β-unsaturated ketimine by an amine and acid affords a ketimine and an aldimine, which is trapped by an alkene and give ketones after hydrolysis. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1218000

LETTER
2939
Tandem Catalytic Triple-Bond Cleavage of Alkyne in Association with
Aldehyde, Alkene, and Water
T
riple-BondCleav
y
age of
A
lkyn
u
e
ng-Mi Cha, Eun-Ae Jo, Chul-Ho Jun*
Department of Chemistry and Centre for Bioactive Molecular Hybrid (CBMH), Yonsei University, Seoul 120-749, Korea
Fax +82(2)31472644; E-mail: junch@yonsei.ac.kr
Received 20 July 2009
with 1:20 of aldehyde/alkyne (route 2). All of these ke-
tones were formed from the C–C bond cleavage of alkyne.
In this reaction, the Rh(I)-catalyzed hydroiminoacylation
of internal alkynes with an aldehyde, followed by a retro-
Abstract: In this tandem reaction the carbon–carbon triple bond of
an alkyne is catalytically cleaved in association with aldehyde, al-
kene, and H2O under catalyst mixtures of Rh(I), 2-amino-3-pi-
coline, primary amine, and acid. The reaction starts with chelation-
assisted hydroacylation of the alkyne with an aldehyde. The retro- Mannich-type fragmentation of the resulting a,b-unsatur-
Mannich-type fragmentation of the resulting a,b-unsaturated
ketimine by an amine and acid affords a ketimine and an aldimine,
which is trapped by an alkene and give ketones after hydrolysis.
ated ketimine by the primary amine and acid generates ke-
tone and aldehyde after hydrolysis of the resulting
ketimine and aldimine. With a large excess amount of
alkyne, aldimine reacts further with alkyne repeatedly.
Encouraged by these results, three-component systems in-
cluding alkene is devised for the C–C triple-bond cleav-
age of alkyne in order to produce two different ketones.
Additional alkene may trap the intermediate aldimine to
afford another ketone after hydrolysis of the resulting
ketimine.
Key words: C–C triple-bond cleavage, C–H bond activation, rho-
dium, homogeneous catalysis
Catalytic C–H1 and C–C bond activation2 of organic sub-
strates by transition-metal complexes is of current interest
in organic synthesis in terms of atom economy. Among
these processes, hydroacylation is an efficient way of di-
rectly transforming an aldehyde to a ketone.3 Chelation-
assisted hydroacylation of alkenes4 or alkynes5 overcomes
many limitations that may occur in hydroacylation reac-
tions: decarbonylation, efficiency, substrates bearing co-
ordination sites at specific positions, etc.6 Also, some
other types of synthetic method of homoallylketones via
selective reaction of alkyne, ethylene, and aldehyde were
reported.7 During the course of our studies on the chela-
tion-assisted hydroacylation of alkynes with aldehyde or
allylamine analogue, we found that the C–C triple bond of
the alkyne could be cleaved by the addition of primary
amine and acid (Scheme 1).8 Depending on the ratio of
substrates, aldehyde to alkyne, products are different.
Based on this protocol we wish to report a structural re-
combination of aldehyde, alkyne, alkene, and H2O by cat-
alyst mixtures for hydroacylation and retro-Mannich-type
fragmentation that give two different ketones through the
C–C triple-bond cleavage of the alkyne.
In a typical experiment, benzaldehyde (1a), 3-hexyne
(2a), 3,3-dimethyl-1-butene (3a), and H2O in the presence
of a cocatalyst system consisting of RhCl(PPh3)3 (4), 2-
amino-3-picoline (5), 4-trifluoromethylbenzoic acid (6),
and n-hexylamine (7a) were reacted in toluene at 150 °C
for 12 hours to produce a mixture of 1-phenylbutan-1-one
(8a), 6,6-dimethylheptan-3-one (9a), and 4,4-dimethyl-1-
phenylpentan-1-one (10a) in 82%:46%:2% isolated yields
based on 1a (Scheme 2). In this reaction, 8a and 9a are the
C–C triple-bond-cleavage products of 2a in combination
with 1a and 3a, while 10a is the direct hydroacylation
product of 3a with 1a.
O
A/B = 3:1
route 1
R1 CHO
R2
C
R1
1) Rh(I)
2-amino-3-picoline
CyNH2, AlCl3
A
+
(aldol of R2CHO)
+
t-Bu
R2
R2
130 °C, 12 h
2) H3O+
PhCHO
Et
Et
+
H2O
+
+
O
A/B = 1:20
B
1a
2a
(1a/2a/3a/H2O = 1:1.5:3:1)
3a
D
R2
route 2
R2
Scheme 1
(Ph3P)3RhCl (4, 5 mol%)
2-amino-3-picoline (5, 100 mol%)
F3CC6H4CO2H (6, 10 mol%)
n-C6H13NH2 (7a, 50 mol%)
toluene, 150 °C, 12 h
With a 3:1 ratio of aldehyde A and alkyne B, the major
component is ketone C and aldol product of aldehyde gen-
erated from the cleavage of alkyne (route 1), while ketone
D is the major component along with a small amount of C
O
O
O
Et
+
+
Ph
t-Bu
Ph
Et
t-Bu
10a
8a
9a
SYNLETT 2009, No. 18, pp 2939–2942
Advanced online publication: 08.10.2009
x
x
.x
x
.2
0
0
9
isolated yield (based on 1a)
8a/9a/10a = 82%:46%:2%
DOI: 10.1055/s-0029-1218000; Art ID: U07109ST
© Georg Thieme Verlag Stuttgart · New York
Scheme 2

2940
K.-M. Cha et al.
LETTER
The reaction mechanism can be explained as shown in To determine the difference in reactivity between alkyne
Scheme 3. The first step must be the condensation of ben- and alkene, the reaction of 1a with equimolar amounts of
zaldehyde (1a) and 2-amino-3-picoline (5) to generate 3-hexyne (2a) and 3,3-dimethyl-1-butene (3a) was carried
aldimine 11a, which reacts with 3-hexyne (2a) to give out at 150 °C for 12 hours in the presence of 4, 5, and 6
a,b-unsaturated ketimine 12a. The retro-Mannich-type without the primary amine (preventing the retro-Mannich
fragmentation of 12a by n-hexylamine (7a) and acid 6 reaction) resulting in the formation of a,b-unsaturated ke-
leads to the formation of imines 15a and 16a through in- tone 13a and 10a in 93%/2% isolated yield (Scheme 4).
termediate 14a. The imine 15a further reacts with alkene Thus, benzaldehyde (1a) reacts almost with alkyne 2a
3a to give ketimine 17a through transimination with 5 and rather than 1-alkene 3a to give 13a predominantly, al-
subsequent chelation-assisted hydroiminoacylation.9 Hydro- though a small amount of hydroacylated ketone 10a from
lysis of imine 16a and 17a affords the corresponding the 1-alkene is inevitably produced in this reaction.
ketones 8a and 9a. Since 17a is produced from 15a, in an
equimolar amount of 16a it is reasonable that the yield of
O
9a is less than that of 8a. In this reaction, only 2% isolated
4 (5 mol%)
5 (100 mol%)
6 (10 mol%)
Et
Ph
Et
Ph CHO
yield of 10a was obtained as a side product from the reac-
tion of a small portion of 11a with 3,3-dimethyl-1-butene
(3a) through the hydrolysis of 18a. In order to obtain the
C–C triple-bond-cleavage products 8a and 9a, imine 11a
should react predominantly with alkyne 2a, not with al-
kene 3a. Fortunately, the alkyne is much more reactive
than the 1-alkene in this chelation-assisted hydroacylation
reaction probably due to a stronger coordinating ability of
the rhodium(I) catalyst to alkynes than alkene. Since the
alkyne is consumed in the initial hydroacylation with 1a,
further reaction of imine 15a now proceeds with 1-alkene
3a to give the ketimine 17a.
t-Bu
Et
13a
+
+
1a
toluene, 150 °C, 12 h
Et
+
H2O
2a
3a
10a
(1a/2a/3a/H2O = 1:1.5:1.5:1)
isolated yield
(based on 1a)
13a/10a = 93%:2%
Scheme 4
Various alkynes, aldehydes, and alkenes were applied in
this C–C triple-bond-cleavage reaction, and the results are
summarized in Table 1. As expected, with benzaldehyde
(1a) the major triple-bond-cleavage products 8 and 9 were
obtained along with the minor hydroacylated product 10.
Even internal alkenes such as norbornene (3c) instead of
a terminal alkene provide a good result.
H2O
N
N
10a
Ph
t-Bu
13a
H2O
Another interesting substrate for this C–C triple bond
cleavage reaction is 3-vinylbenzaldehyde (19a) since a
subsequent structural reorganization is possible under this
protocol (Scheme 5).
18a
4
3a
(5)
NH2
2a
N
N
N
N
N
1a
O
O
Et
4
– H2O
H
Ph
12a
Et
Et
Et
Ph
H
Et
6 + 7a
11a
O
Et
H
n-C6H13
Ph
19a
20a
n-C6H13
n-C6H13
NH
n-C6H13
Et
N
N
H2O
N
+
8a
Scheme 5
Ph
Et
Et
Et
16a
15a
4 + 5
When the reaction of 3-vinylbenzaldehyde (19a) with 3-
hexyne (2a) was performed at 130 °C for 72 hours in the
presence of a catalytic system of 4, 5, 6, and cyclohexyl-
amine (7b), a 42% isolated yield of dialkyl ketone 20a
was obtained along with 21a and 22a in 25% and 14% iso-
lated yields (Scheme 6). Compound 21a is an intermedi-
ate for this transformation while 22a is a reduced form of
21a. This type of reduction may be derived from the reac-
tion of CyNH2 (7b) and 21a via Rh(I)-catalyzed transfer
hydrogenation.10 The reaction of 4-vinylbenzaldehyde
(19b) was also used as a substrate for this reaction, and
similar results were obtained as in Scheme 6.11
14a
3a
H2O
N
N
9a
t-Bu
Et
17a
Scheme 3 Proposed mechanism for the C–C triple-bond cleavage of
2a in association with 1a and 3a through hydroacylation of alkyne,
retro-Mannich-type fragmentation, and hydroiminoacylation of 1-
alkene with the resulting aldimine
The reaction mechanism can be proposed as shown in
Scheme 7. Initially formed a,b-unsaturated ketimine 12b
Synlett 2009, No. 18, 2939–2942 © Thieme Stuttgart · New York

LETTER
Triple-Bond Cleavage of Alkyne
2941
Table 1 C–C Triple-Bond Cleavage of Alkyne 2 with Aldehyde 1 and Alkene 3 under the Catalyst System of 4, 5, 6, and 7aa
4 (5 mol%)
5 (100 mol%)
6 (10 mol%)
7a (50 mol%)
R2
O
O
O
O
H2O
R2
+
+
+
+
R1
H
R1
R3
R2
R1
R3
R3
R2
toluene, 150 °C, 24 h
1
2
3
8
9
10
Entry
Aldehyde (R1)
Alkyne (R2)
Olefin (R3)
Isolated yield (%)b
8
9
10
1
2
3
4
5
1a Ph
2a Et
2a
3b n-Bu
8a 86
8a 79
8b 73
8c 75
8d 75
9b 56
9c 50
9d 35c
9c 37
9a 39
10b 2
10c 5
10a 3
10d 7
10e 6
1a
3c norbornene
1a
2b Me
2a
3a t-Bu
3c
1b n-C5H11
1c PhCH2CH2
2a
3a
a Reactions conditions: aldehyde 1 (0.8 mmol), alkyne 2 (1.5 equiv), olefin 3 (3 equiv), and H2O (1 equiv, based on aldehyde 1).
b Isolated yield is calculated based on aldehyde 1.
c 2% of symmetric dialkyl ketone (2,2,8,8-tetramethylnonan-5-one) derived from C–C bond activation of 9d is included.
from the reaction of 19a with 2a undergoes retro-
Mannich-type fragmentation by 6 and 7b generating 16b
hydroimination
of alkyne
retro-
N
N
and aldimine 15b. Again these two intermediates react to
form ketimine 23a, which is hydrolyzed to afford 20a as
a final product.
N
N
Mannich
19a
Et
Et
Cy
N
Et
+
4 + 5
6 + 7b
+
– H2O
2a
H
Et
In summary, we have demonstrated the catalytic C–C
triple-bond cleavage of an alkyne in association with alde-
hyde, alkene, and H2O under the catalyst mixture of Rh(I),
2-amino-3-picoline, carboxylic acid, and primary amine
to produce ketones. The reaction consists of a hydro-
iminoacylation of alkyne with the aldehyde, subsequent
retro-Mannich-type fragmentation of the resulting a,b-un-
saturated ketimine generating a ketimine and an aldimine,
and hydroiminoacylation of the alkene with the interme-
diate aldimine to give another ketimine. Hydrolysis of two
resulting ketimines by H2O produces two different ke-
tones. When this reaction protocol was applied to 3- or 4-
vinylbenzaldehyde and an alkyne, a diketone compound
16b
12b
15b
4 + 5
reduction
of alkene
H2O
7b + 4
22a
21
N
N
H2O
Et
20a
Cy
N
Et
23a
Scheme 7 Proposed mechanism for the formation of C–C triple-
bond cleavage product 2a in association with 19a
O
4 (5 mol%)
Et
5 (50 mol%)
H
6 (10 mol%)
was obtained through the structural reorganization of sub-
strates.
H2O
+
+
CyNH2 (7b, 50 mol%)
toluene, 130 °C, 72 h
Et
19
2a
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
(19/2a/H2O = 1:1.5:1)
O
O
O
Et
+
Et
Et
Acknowledgment
+
O
This work was supported by the Korea Research Foundation Grant
funded by the Korean Government (MOEHRD, KRF-2008-313-
C00483) and 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 CBMH. K.-M. C. and E.-A. J. acknowledge the fellowships of
the BK21 program of the Ministry of Education and Human Re-
sources Development.
Et
21
22
20
Isolated yield (based on 19)
19a 3-vinyl
19b 4-vinyl
20a/21a/22a = 42%:25%:14%
20b/21b/22b = 39%:11%:25%
Scheme 6
Synlett 2009, No. 18, 2939–2942 © Thieme Stuttgart · New York

2942
K.-M. Cha et al.
LETTER
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Synlett 2009, No. 18, 2939–2942 © Thieme Stuttgart · New York

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