Rhodium-catalyzed intermolecular hydroacylation of 1-alkynes: Effect of phosphines and MK-10 on the reaction selectivity

Article abstract of DOI:10.1016/j.jorganchem.2006.12.018

The use of bulky ligands in the rhodium-catalyzed reaction of aldehydes 7 (R¹ = Ph) and 18 with 1-octyne increased the selectivity for ketones 13 and 20, to the detriment of ketones 12 and 19. Bulky phosphines reduced the hydroacylation reactio

Full text of DOI:10.1016/j.jorganchem.2006.12.018

Journal of Organometallic Chemistry 692 (2007) 1628–1632
www.elsevier.com/locate/jorganchem
Communication
Rhodium-catalyzed intermolecular hydroacylation of 1-alkynes:
Effect of phosphines and MK-10 on the reaction selectivity
a,b
Xiomara Y a´ n˜ ez Rueda , Sergio Castill o´ n
a,
*
a
Department of Analytical Chemistry and Organic Chemistry, Universitat Rovira i Virgili, Tarragona, Spain
b
Department of Chemistry, University of Pamplona, Pamplona, Norte de Santander, Colombia
Received 13 December 2006; received in revised form 19 December 2006; accepted 19 December 2006
Available online 23 December 2006
Abstract
1
The use of bulky ligands in the rhodium-catalyzed reaction of aldehydes 7 (R = Ph) and 18 with 1-octyne increased the selectivity for
ketones 13 and 20, to the detriment of ketones 12 and 19. Bulky phosphines reduced the hydroacylation reaction rate, leading to com-
petition from the addition of the benzoic acid co-catalyst to the alkynes. This competing reaction can be suppressed by using the clay
Montmorillonite K 10 (MK-10) as the co-catalyst instead of benzoic acid.
ꢀ
2006 Elsevier B.V. All rights reserved.
Keywords: Hydroacylation; Alkynes; Rhodium; Catalysis; Selectivity; Montmorillonite MK-10
1
. Introduction
cess starts with the transformation of the aldehyde 7 into
the aldimine 8 by reaction with 2-amino-3-picoline in the
presence of benzoic acid as a co-catalyst. The aldimine then
reacts with the alkyne in the presence of Wilkinson’s cata-
lyst to give the ketimine 9, which is hydrolyzed under these
conditions to the a,b-unsaturated ketone 10 (Scheme 3).
The regioselectivity of this reaction differs from that
obtained by reacting aldehydes 1 and 2.
The intermolecular hydroacylation of alkynes often
requires the presence of coordinating heteroatoms in the
aldehyde moiety in order to avoid the competing decarbox-
ylation reaction. For example, benzaldehyde bearing PPh2
[
1] (1) or OH [2] (2) groups in the ortho position has been
successfully used in the hydroacylation of terminal as well
as disubstituted alkynes, providing the a,b-unsaturated
ketones 3 and 4 of E configuration, respectively (Scheme
1
Using the aldimine approach, it was found that when R
was an alkyl group, a small percentage of the product was
1
) [3]. Compounds 3 were reduced in situ to the saturated
the E isomer 11. By contrast, 11 was exclusively obtained
when R was a bulky substituent such as a tert-butyl group.
2
ketone except when a bulky substituent was present
1
2
t
(
R = H, R = Bu). In a similar approach, alkyl aldehydes
, react with alkynes in the presence of a rhodium catalyst
to yield 1,2-disubstituted alkenes 6 with an E configuration
This indicates that the regioselectivity of the reaction is
very sensitive to steric hindrance of the substituents.
The strategy based on the use of aldimine derivatives is
synthetically more flexible than the other approaches,
although compounds of general structure 10 are usually
favored. In the present work, we show that the selectivity
in the final ketone can be modified to give increasing
amounts of ketones 11, by varying the steric hindrance
induced by the phosphines and that Montmorillonite
MK-10 can advantageously replace the benzoic acid in
order to avoid secondary reactions.
5
(
Scheme 2) [4].
Jun et al. reported the rhodium-catalyzed intermolecular
hydroacylation of alkynes [5,6] by transforming in situ the
aldehyde into a piridyl-aldimine [7]. Specifically, the pro-
*
Corresponding author. Tel.: +34 977 559556; fax: +34 977 558446.
E-mail address: sergio.castillon@urv.net (S. Castillon).
´
0
022-328X/$ - see front matter ꢀ 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2006.12.018

X.Y. Rueda, S. Castill o´ n / Journal of Organometallic Chemistry 692 (2007) 1628–1632
1629
O
O
data. The esters 15–17 resulted from the addition of ben-
zoic acid to octyne. The results were found to be reproduc-
ible under these conditions.
H
R1
R2
R2
+
R1
X
X
We additionally tested the use of phosphine ligands with
1
2
X= PPh
X=OH
2
X=PPh
2
[Rh(μ-Cl)(cod)]
2
3 X= PPh
2
cone angles [8] larger than that of PPh . The results, sum-
3
2
X=OH [Rh(μ-Cl)(cod)] /dppf
4 X=OH
marized in Table 1, showed that when the cone angle of the
ligand increased from 145ꢁ (triphenylphosphine) to 194ꢁ
(tri-o-tolylphosphine) the selectivity for ketone 12
decreased from 80% to 8%, while higher amounts of the
E isomer 13 was produced under these conditions (entries
SR2
SR2
O
O
R3
R1
+
R1
R3
H
5
6
1
–6, Table 1).
Scheme 1.
This finding can be explained by phosphine ligands with
larger cone angles inducing greater steric hindrance. Signif-
icantly, when the bulky ligands tri-tert-butylphosphine or
tri-o-tolylphosphine were used, the formation of ketone
13 was favored over ketone 12 (entries 5 and 6, Table 1).
In all cases, esters 15–17 were obtained and the cis isomer
O
benzoic acid
H O
+
N
R1
N
H
NH2
N
-
R1
2
H
1
4 was not detected. Furthermore, when the ketone conver-
7
8
sion was low, the percentage of ester increased. Thus, when
the phosphine ligand was P BuPh or PCy (entries 3 and 4,
R2
t
2
3
[
RhCl(PPh
3
)
3
]
Table 1), esters constituted over 50% of the products gen-
erated by the reaction, and when P(o-tolyl) was used, this
3
percentage reached 75%.
O
O
benzoic acid
The use of a bulky phosphine decreases the value of k2,
making the addition of benzoic acid to the alkyne more com-
petitive (Scheme 3). As a consequence, the concentrations of
benzoic acid and alkyne are lowered, further decreasing the
overall reaction rate of the hydroacylation process.
The above results indicate that the use of phosphine
ligands with larger cone angles favors the formation of
ketone 13 with respect to ketone 12, and leads to decreased
conversion as well as increased formation of the unsatu-
rated esters such that, when the phosphine cone angle
exceeds 160ꢁ, the esters are the major reaction products.
Recently we developed a novel catalytic system using
Montmorillonite K-10 (MK-10) as a co-catalyst in chela-
tion-assisted intermolecular hydroacylation [9]. MK-10
can be employed as a reusable acid co-catalyst, instead of
benzoic acid, for the condensation of aldehydes and amino-
pyridines to provide the intermediate aldimine (Scheme 2).
In addition, we hypothesized that, unlike benzoic acid,
MK-10 would not undergo an addition reaction with the
alkynes.
R2
N
N
R1
R1
R2
R1
H
2
O
R2
11
10
9
Scheme 2.
COOH
k1
C
6
H
13
+
15-17
O
COOH
N
N
C
H
+
H
NH
2
N
[
Rh] / PR3
1
2-13
6 13
C H
When MK-10 was used in the intermolecular catalytic
hydroacylation of benzaldehyde and 1-octyne with
k
2
[
RhCl(PPh ) ] as the catalyst, under conditions similar to
3 3
Scheme 3.
those used previously [9], 85% conversion was achieved
entry 7, Table 1); unexpectedly, however, the a-b-unsatu-
(
2
. Results and discussion
rated ketones 12 and 13 were obtained in a ratio of 75:25.
Finally, when tricyclohexylphosphine was used in the pres-
ence of MK-10 at 80 ꢁC for 12 h (entry 8, Table 1), the con-
version was found to be 20%, and the enones 12 and 13
were obtained in a 60:40 ratio. Notably, none of the previ-
ously described reactions produced esters 15–17 or the cis-
ketone 14 at detectable levels, indicating that the use of
MK-10 in the Rh-catalyzed intermolecular hydroacylation
of alkynes avoids the formation of ester by-products.
Initially, benzaldehyde was reacted with 1-octyne in the
presence of 2-amino-3-picoline and benzoic acid, using
Rh(l-Cl)(cod)]2 /PPh3 as a catalyst [5]. After 12 h at
[
8
0 ꢁC, 90% conversion was obtained with 80% selectivity
for the ketone 12 (entry 1, Table 1). The by-products of
the reaction were identified as the a,b-unsaturated esters
À1
1
5–17, on the basis of IR (band at 1735 cm ) and NMR

1630
X.Y. Rueda, S. Castill o´ n / Journal of Organometallic Chemistry 692 (2007) 1628–1632
Table 1
Influence of the ligand cone-angle on the selectivity of the rhodium-catalyzed intermolecular hydroacylation of 1-octyne with benzaldehyde
a
O
O
O
C H
6
13
Ph
Ph
2 3
[Rh(μ-Cl)(cod)] /PR
+
Ph
C H
+
6
13
O
benzoic acid
H13C6
14
2
-amine-3-picoline
H
H
C H
+
6
13
12
13
Toluene
1
2h, 80 C
O
O
˚
O
C H
6
13
+
Ph
Ph
O
+
13
Ph
O
O
C
H
6
C H
6
13
15
16
17
b
c
c
Entry
PR
3
(ꢁ)
Conv. (%)
Products (%)
1
2
13
14
15
16
17
d
1
PPh
P(m-OMeC
3
145
150
164
170
182
194
145
170
90
85
40
45
60
20
85
20
80
75
35
35
20
8
–
–
–
–
–
–
–
–
–
–
10
15
35
40
30
40
–
5
10
10
15
20
25
–
5
–
5
–
–
10
–
–
2
3
4
5
6
6
H
4
)
3
t
P BuPh
PCy
2
15
10
30
17
25
40
3
t
P Bu
P(o-tolyl)
PPh
PCy
3
3
d,e
7
f
3
75
60
8
3
–
–
a
Standard conditions: benzaldehyde (2 mmol), 1-octyne (4 mmol), 2-amino-3-picoline (0.8 mmol), benzoic acid (0.4 mmol), [Rh(l-Cl)(cod)]
= 1:3, 2 ml of toluene, 12 h, 80 ꢁC.
2
(5 mol %),
ratio Rh/PR
b
3
Cone angle [8].
c
d
e
f
Determined by GC.
[
3 3
RhCl(PPh ) ] was used as catalyst.
MK-10 (83 mg) was used instead of benzoic acid, 110 ꢁC, 2 h.
MK-10 (83 mg) was used instead of benzoic acid, 80 ꢁC, 12 h.
The intermolecular hydroacylation reaction of non-aro-
matic aldehydes such as cyclohexanecarbaldehyde (18) and
-hexyne in the presence of 2-amino-3-picoline and benzoic
presence of benzoic acid or MK-10. The conversions were
found to be 50% and 40%, respectively, whereas the selec-
tivity of the trans a,b-unsaturated ketone 20 increased to
1
acid using Wilkinson’s catalyst has been investigated previ-
ously. When we performed this reaction under the condi-
tions used in the previous study, 100% conversion and a
ratio of 19/20 = 81:19 were obtained in 2 h of reaction to
30% and 35%, respectively (entries 3 and 4, Table 2).
t
When P Bu was used, the conversion was 40% and the
3
percentage of ketone 20 was 40%. The cis isomer was
not detected among the products of any of the reactions
(entry 5, Table 2).
8
2
0 ꢁC, consistent with the previous report (entry 1, Table
). No ester by-products were detected in this case. When
MK-10 was used instead of benzoic acid, the conversion
decreased to 70%, and in agreement to the observed in
Table 1 E isomer 20 increased slightly (entry 3, Table 2).
The effect of sterically demanding ligands was also
3. Conclusions
In summary, we have shown here that the use of steri-
cally demanding ligands in the rhodium-catalyzed intermo-
lecular hydroacylation of alkynes increases the selectivity
explored. The reaction was carried out with PCy in the
3
Table 2
a
Rhodium-catalyzed intermolecular hydroacylation of 1-octyne with cyclohexanecarbaldehyde
Entry
Catalytic system
PR
3
Co-catalyst
Conv. (%)
19
20
1
2
3
4
5
a
[RhCl(PR
[RhCl(PR
[Rh(lCl)(cod)]
[Rh(lCl)(cod)]
[Rh(lCl)(cod)]
3
)
)
3
3
]
]
PPh
PPh
PCy
3
Benzoic acid
MK-10
Benzoic acid
MK-10b
Benzoic acid
100
70
50
40
40
81
75
70
65
60
19
25
30
35
40
b
3
3
2
2
2
3
PCy
3
t
P Bu
3
Standard conditions: 18 (2 mmol), 1-octyne (4 mmol, 600 ll), 2-amino-3-picoline (0.8 mmol), catalytic system (5 mol%), benzoic acid (0.4 mmol) or
MK-10 (83 mg), toluene (2 ml), 2 h, 80 ꢁC.
b
Temperature 110 ꢁC.

X.Y. Rueda, S. Castill o´ n / Journal of Organometallic Chemistry 692 (2007) 1628–1632
1631
for ketones 13 and 20 with an E configuration with respect
to ketones 12 and 18, respectively. We found that the use of
sterically demanding ligands reduced the hydroacylation
rate, leading to competitive addition of the benzoic acid
co-catalyst to the alkynes to give esters. This secondary
reaction could, however, be suppressed by using MK-10
as the co-catalyst for the formation of the imine and the
hydrolysis of ketimine.
(E)-1-Phenyl-non-2-en-1-one (13). Obtained from the
1
mixture with 12. H NMR (400 MHz, CDCl ) d in
3
ppm: 7.80 (d, J = 6.9 Hz, 2H), 7.55 (d, J = 6.2 Hz, 1H),
7.42 (t, J = 7.3 Hz, 2H), 6.82 (dt, J = 15.6 and 6.9 Hz,
1Ha), 6.10 (dt, J = 15.9, 1.6 Hz, 1Hb). 2.2 (qd,
J = 6.9, 1.6 Hz, 2H), 1.5–1.2 (m, 8H), 0.91 (t, J = 7.6 Hz,
3H, CH3).
(E)-Oct-1-enyl benzoate (15). Obtained from the mix-
1
ture with 16. H NMR (400 MHz, CDCl TMS) d in
3
,
4
. Experimental
ppm: 8.11 (dd, J = 7.2, 1.1 Hz, 2H), 7.59 (tt, J = 7.2,
.1 Hz, 1H), 7.49 (t, J = 7.3 Hz, 2H), 7.31 (dt, J = 12.4
1
All of the starting materials, reagents, MK-10 and phos-
and 1.6 Hz, 1Ha), 5.61 (dt, J = 12.4 and 7.2 Hz, 1Hb),
phines used in this work were purchased and used without
further purification except the aldehydes, which were dis-
tilled prior to use. All solvents were distilled prior to use.
2.07 (qd, J = 7.6, 1.2 Hz, 2H, –CH ), 1.50–1.20 (m, 8H),
2
0.90 (t, J = 5.9 Hz, 3H, –CH3).
1-Pentyl-vinyl benzoate (16). IR 1735 cm . H NMR
(400 MHz, CDCl TMS) d ppm 8.05 (dd, J = 7.2, 1.5 Hz,
À1
1
1
13
H and
C NMR spectra were recorded using a
3
,
3
00 MHz and 400 MHz apparatus, with CDCl as the sol-
2H), 7.60 (tt, J = 7.5, 1.5 Hz, 1H), 7.47 (t, J = 7.3 Hz,
2H), 4.85 (d, J = 1.4 Hz, 1H), 4.83 (d, J = 1.4 Hz, 1H),
3
vent and Me Si as the internal reference. Flash column
4
chromatography was performed using silica gel 60 A CC
2.57 (t, J = 7.6 Hz, 2H, –CH ), 1.50–1.20 (m, 8H), 0.88
(t, J = 7.2 Hz, 3H, –CH3). C NMR (100.6 MHz, CDCl3)
d ppm 164.8, 156.8, 133.3, 129.9, 128.5, 101.3, 33.4, 31.6,
2
1
3
(
230–400 mesh). The catalytic reactions were monitored
by GC on a Hewlett–Packard 5890A. Conversion was mea-
sured in an HP-5 column (25 m · 0.2 mm B).
28.7, 26.5, 22.5, 14.0.
À1
(
E)-Oct-1-enyl benzoate (17). IR (CH Cl ) 1733 cm
.
2
2
1
4.1. General procedure for the intermolecular hydroacylation
of alkynes
H NMR (400 MHz, CDCl TMS) d ppm 8.10 (d,
3,
J = 6.9 Hz, 2 H, Ph), 7.61 (d, J = 6.2 Hz, 1H, Ph), 7.50
t, J = 7.3 Hz, 2H, Ph), 7.26 (dt, J = 6.4 and 1.6 Hz,
(
A mixture of aldehyde (2 mmol), 1-octyne (4 mmol,
00 ll), 2-amino-3-picoline (0.8 mmol), benzoic acid
0.4 mmol), [Rh(l-Cl)(cod)]2 (0.054 mmol), and PR3
1Ha), 5.01 (dt, J = 7.4, 6.4 Hz, 1Hb), 2.28 (qd, J = 7.4,
1.6 Hz, 2H, –CH2), 1.50–1.20 (m, 8H), 0.90 (t,
6
(
(
1
3
J = 7.4 Hz, 3H, –CH3). C NMR (100.6 MHz, CDCl ) d
3
0.162 mmol), or alternatively 0.05 mmol of [RhCl(PPh ) ],
ppm 163.6, 134.1, 133.4, 129.9, 128.5, 115.0, 31.6, 29.2,
28.8, 24.6, 22.6, 14.0.
3
3
was heated at 80 ꢁC for 12 h in 3 ml of toluene. The reac-
tion mixture was allowed to cool to room temperature
and then purified by flash chromatography with hexane–
AcOEt 98:2. The structures of the isolated compounds
1
1-Cyclohexyl-2-hexyl-propenone (19). H NMR (400
MHz, CDCl TMS) d in ppm: 5.9 (s, 1H), 5.7 (s, 1H), 2.5
3
,
(t, J = 7.4 Hz, 2H), 1.5–1.2 (m, 8H), 0.9 (t, J = 5.9 Hz,
1
13
13
were determined from their H and C NMR spectra.
3H, –CH3). C NMR (100.6 MHz, CDCl ) d in ppm:
3
203.5, 148.0, 123.2, 42.0, 32.3, 31.6, 29.1, 28.5–27.1 (5C),
4
.2. General procedure for the intermolecular hydroacylation
22.6, 14.0.
of alkynes using [Rh(l-Cl)(cod)] /PR /Montmorillonite
(E)-1-Cyclohexyl-2-nonenone (20). Spectroscopic data
obtained from the mixture with 18. H NMR (400 MHz,
2
3
1
(
MK-10)
CDCl TMS) d ppm 6.8 (d, J = 15.9 and 6.9 Hz, 1Ha),
3
,
A mixture of aldehyde (2 mmol), 1-octyne (4 mmol,
00 ll), 2-amino-3-picoline (0.8 mmol), MK-10 (83 mg),
6.1 (d, J = 15.9 Hz, 1Hb). 2.2 (q, J = 6.9 Hz, 2H), 1.5–1.2
(m, 8H), 0.91 (t, J = 5.9 Hz, 3H, CH3).
6
[
Rh(l-Cl)(cod)]2 (0.054 mmol), and PR3 (0.162 mmol)
was heated at 110 ꢁC for 2 h in 3 ml of toluene. The reac-
tion mixture was allowed to cool to room temperature
and then purified by flash chromatography with hexane–
AcOEt 98:2.
Acknowledgements
The authors gratefully acknowledge the financial sup-
port of DGESIC BQU2005-01188 (Ministerio de Ciencia
y Tecnolog ´ı a, Spain), technical assistance from the Servei
de Recursos Cientifics (URV). X.Y. Acknowledges finan-
cial support from the University of Pamplona (Colombia)
and the University Rovira i Virgili (Spain).
Main spectroscopic data of ketones 12, 13, 19 and 20,
and of esters 15–17.
À1
1
2
-Hexyl-1-phenyl-2-propenone (12). IR: 1685 cm . H
NMR (400 MHz, CDCl ) d in ppm: 7.80 (dd, J = 7.2,
3
1
.5 Hz, 2H), 7.55 (tt, J = 7.1, 1.5 Hz, 1H), 7.43 (t,
J = 7.3 Hz, 2H), 5.82 (s, 1H), 5.60 (s, 1H), 2.56 (t,
J = 7.4 Hz, 2H), 1.5–1.2 (m, 8H), 0.90 (t, J = 5.9 Hz, 3H,
References
1
3
–
1
2
CH3). C NMR (100.6 MHz, CDCl ) d in ppm: 198.5,
48.5, 137.9, 132.1, 129.5, 128.1, 125.1, 32.2, 31.5, 29.0,
8.1, 22.5, 14.0.
3
[
[
1] C.H. Jun, H. Read, Bull. Korean Chem. Soc. 16 (1995) 1135.
2] K. Kokubo, K. Matsumasa, M. Miura, M. Nomura, J. Org. Chem. 62
(1997) 4564.

1632
X.Y. Rueda, S. Castill o´ n / Journal of Organometallic Chemistry 692 (2007) 1628–1632
[
[
3] For an intramolecular version see: H.D. Bendorf, C.M. Colella, E.C.
Dixon, M. Marchetti, A.N. Matukonis, J.D. Musselman, T.A. Tiley,
Tetrahedron Lett. 43 (2002) 7031.
4] (a) M.C. Willis, H.E. Randell-Sly, R.L. Woodward, S.J. McNally,
G.S. Currie, J. Org. Chem. 71 (2006) 5291;
[6] (a) Hydroacylation of disubstituted alkynes with aldehydes without the
chelation assisted strategy by using Ni(0) catalysts has been reported.
T. Tsuda, T. Kiyoi, T. Saegusa, J. Org. Chem. 55 (1990) 2554;
(b) T. Tsuda, T. Kiyoi, T. Miyane, T. Saegusa, J. Am. Chem. Soc. 110
(1988) 8570.
(
b) M.C. Willis, H.E. Randell-Sly, R.L. Woodward, G.S. Currie, Org.
[7] (a) C.H. Jun, C.W. Moon, D.Y. Lee, Chem. Eur. J. 8 (2002) 2423;
(b) C.H. Jun, D.Y. Lee, H. Lee, J.B. Hong, Angew. Chem. Int. Ed.
Engl. 39 (2000) 3070;
Lett. 7 (2005) 2249.
5] (a) C.H. Jun, H. Lee, J.B. Hong, B.I. Kwon, Angew. Chem. Int. Ed.
[
4
(
1 (2002) 2146;
b) D.Y. Lee, B.S. Hong, E.G. Cho, H. Lee, C.H. Jung, J. Am. Chem.
Soc. 125 (2003) 6372;
c) C.H. Jun, H. Lee, Pure Appl. Chem. 76 (2004) 577.
(c) C.H. Jun, J.B. Hong, Org. Lett. 1 (1999) 2161.
[8] C.A. Tolman, Chem. Rev. 77 (1977) 313.
[9] X. Y a´ n˜ ez, C. Claver, S. Castill o´ n, E. Fern a´ ndez, Tetrahedron Lett. 44
(2003) 1631.
(