Iridium-catalyzed addition of aroyl chlorides and aliphatic acid chlorides to terminal alkynes

Article abstract of DOI:10.1021/ja209679c

Iridium complexes show high catalytic activity in intermolecular additions of acid chlorides to terminal alkynes to afford valuable (Z)-β-chloro- α,β-unsaturated ketones. Ligands in the catalytic system play a crucial role in this reaction. An N-heterocyclic carbene (NHC) is an efficient ligand for the addition of aroyl chlorides, while dicyclohexyl(2-methylphenyl) phosphine (PCy₂(o-Tol)) is indispensable for the reaction of aliphatic acid chlorides. The addition reactions proceed regio- and stereoselectively with suppression of decarbonylation and β-hydrogen elimination, which have been two major intrinsic problems in transition-metal-catalyzed reactions. Stoichiometric reactions of active iridium catalysts with aroyl chlorides and aliphatic acid chlorides are carried out to gain insights into the reaction mechanisms.

Full text of DOI:10.1021/ja209679c

Article
pubs.acs.org/JACS
Iridium-Catalyzed Addition of Aroyl Chlorides and Aliphatic Acid
Chlorides to Terminal Alkynes
Tomohiro Iwai,† Tetsuaki Fujihara, Jun Terao, and Yasushi Tsuji*
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku,
Kyoto 615-8510, Japan
S
* Supporting Information
ABSTRACT: Iridium complexes show high catalytic activity
in intermolecular additions of acid chlorides to terminal
alkynes to afford valuable (Z)-β-chloro-α,β-unsaturated
ketones. Ligands in the catalytic system play a crucial role in
this reaction. An N-heterocyclic carbene (NHC) is an efficient
ligand for the addition of aroyl chlorides, while dicyclohexyl(2-
methylphenyl)phosphine (PCy2(o-Tol)) is indispensable for
the reaction of aliphatic acid chlorides. The addition reactions
proceed regio- and stereoselectively with suppression of
decarbonylation and β-hydrogen elimination, which have been two major intrinsic problems in transition-metal-catalyzed
reactions. Stoichiometric reactions of active iridium catalysts with aroyl chlorides and aliphatic acid chlorides are carried out to
gain insights into the reaction mechanisms.
in the reactions, facile β-hydrogen elimination11 from species B
inevitably occurs to afford hydride species C (step c). Hence,
the reactions often become more unselective.
On the other hand, oxidative addition of acid chlorides to a
INTRODUCTION
■
Highly atom-efficient1 additions of carbonyl functionalities to
carbon−carbon multiple bonds are extremely promising in
realizing valuable and environmentally benign organic trans-
metal center is a facile step.12 Thus, acid chlorides are
promising substrates in the addition reaction.13 The addition
to alkynes is particularly useful, as both carbonyl and chloro
functionalities can be introduced atom-economically and
simultaneously to afford valuable β-chloro-α,β-unsaturated
ketones.14 In a transition-metal-catalyzed reaction, Miura and
co-workers reported a pioneering rhodium-catalyzed addition
of aroyl chlorides to terminal alkynes.13a However, in their case,
carbonyl functionality was completely lost by the facile
decarbonylation reaction from the product during the reaction.
Tanaka and co-workers found that in the presence of a rhodium
catalyst, perfluorinated acid chlorides,15a chloroacetyl chlo-
rides,15b and α-keto acid chlorides15c successfully added to
terminal alkynes without the decarbonylation. However, to
prevent decarbonylation, the substrates were limited to these
acid chlorides.16 Friedel−Crafts-type additions of acid chlorides
to alkynes using a stoichiometric or catalytic amount of a Lewis
acid are known.17 However, these reactions often suffer from
the narrow scope of applicable substrates and/or low
stereoselectivity of products.
formations.2 In these addition reactions, the most common
carbonyl sources are aldehydes (hydroacylation).3 Oxidative
addition of aldehydes to different metal centers (X = H, step a
in Scheme 1) has been reported.4 However, after oxidative
Scheme 1. Reaction of Aldehydes and Acid Chlorides with a
Catalyst Center
addition, the carbonyl functionality is often lost via decarbon-
ylation5 from the resulting acyl metal species A (step b).
Therefore, catalytic additions of aldehydes to unsaturated
compounds often suffer from low selectivity and low yields. To
suppress such undesirable decarbonylation reactions, (1)
intramolecular addition,6 (2) carbon monoxide pressure,7
and/or (3) substrates having proper directing groups8 have
often been indispensable.9,10 In addition, when aliphatic
aldehydes (such as G = R′CH2−CH2 in Scheme 1) are used
Here, we report that an iridium complex bearing a suitable
ligand successfully catalyzes the addition of acid chlorides to
terminal alkynes, giving (Z)-β-chloro-α,β-unsaturated ketones
regio- and stereoselectively. Importantly, both aroyl chlorides18
and aliphatic acid chlorides can be utilized in the addition
Received: October 14, 2011
Published: December 13, 2011
© 2011 American Chemical Society
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reaction with suppression of decarbonylation and β-hydrogen
elimination, which have been two major intrinsic problems
in transition-metal-catalyzed reactions.19 The key to the success
of such a wide substrate applicability in the present iridium-
catalyzed reaction is the appropriate choice of ligands depend-
ing on the substrates.
with high (Z)-selectivity even at 90 °C (91% yield, Z/E = 99/1;
entry 8). In contrast, with phosphines such as SPhos21 and
RuPhos21 (Figure 1), the decarbonylated product 4aa was
obtained fairly selectively as a major product in 61% and 72%
yields, respectively (entries 9 and 10). Thus, the ligand in the
catalytic system played a critical role in determining the
selectivity of the products. As for solvents, in dioxane the
product 3aa was afforded in 86% yield, whereas the reaction did
not proceed in propionitrile and N,N-dimethylformamide
under conditions identical to those of entry 8.
RESULT AND DISCUSSION
■
First, the addition of aroyl chlorides was examined,18 because
aryl−metal species (B: with G = Ar, Scheme 1) generated by
decarbonylation do not undergo β-hydrogen elimination. In
Table 1, the reaction of benzoyl chloride (1a) with phenylacetylene
As reported preliminarily,18 the corresponding β-chloro-α,
β-unsaturated aromatic ketones (3) were obtained regio- and
(Z)-stereoselectively from various aroyl chlorides and terminal
alkynes. Representative examples were shown in Table 2.
Table 1. Effect of Ligands on the Addition of Benzoyl
a
Chloride (1a) to Phenylacetylene (2a)
Table 2. Addition of Aroyl Chlorides (1) to Terminal
a
Alkynes (2) without Decarbonylation
b
c
b
entry
ligand
3aa % yield (Z/E)
4aa % yield
1
2
PPh3
PCy3
6
53 (94/6)
37 (88/12)
20 (89/11)
46 (91/9)
37 (87/13)
88 (98/2)
<1
12
9
3
PCy2(o-Tol)
4
PCy2(o-biphenyl)
XPhos
4
5
28
4
a
6
IMes·HCl/t-BuOK
IPr·HCl/t-BuOK
[IrCl(cod)(IPr)]
Conditions: Aroyl chlorides (1, 0.50 mmol), alkynes (2, 0.75 mmol),
7
2
[IrCl(cod)(IPr)] (0.025 mmol, 5.0 mol %), toluene (1.0 mL), at 90 °C,
d
e
b
c
8
(91) (99/1)
<1
61
for 20 h. Isolated yields. Z/E > 99/1.
9
SPhos
12
9
e
Electron-rich (1b) and electron-poor aroyl chlorides (1c)
reacted smoothly with 2a without decarbonylation to give 3ba
and 3ca in high yields (entries 1 and 2). An aliphatic terminal
alkyne (2b) also provided the adduct 3ab (entry 3).
10
RuPhos
72 (70)
a
Conditions: Benzoyl chloride (1a, 0.50 mmol), phenylacetylene
(2a, 0.75 mmol), [IrCl(cod)]2 (0.0125 mmol, 2.5 mol %), added ligand
(0.025 mmol, 5.0 mol %), toluene (1.0 mL), under reflux, for 20 h.
b
Yield based on the GC internal standard technique by using tridecane
For aliphatic acid chlorides, the most active catalyst for aroyl
chlorides, [IrCl(cod)(IPr)] (Table 2), was not effective. With
this [IrCl(cod)(IPr)] as a catalyst, the reaction of stearoyl
chloride (1d) with 2b afforded the desired product (3db) in
only 29% isolated yield (entry 1, Table 3). Combinations of the
Ir precursor [IrCl(cod)]2 and a wide variety of ligands induced
little or no catalytic activity (entries 2−8). In these cases, a
considerable amount of 1-heptadecene (5) was formed via
decarbonylation followed by facile β-hydrogen elimination. Like
aroyl chlorides, phenylacetyl chloride (1e) does not undergo
β-hydrogen elimination after the decarbonylation. However, even
for 1e, [IrCl(cod)(IPr)] was not an active catalyst (entry 10).
The [IrCl(cod)]2/RuPhos catalyst system also gave a
complex mixture (entry 11). Among the ligands examined,
PCy2(o-Tol)20 is a very unique ligand and brought about a
highly active catalyst system for both 1d and 1e to afford the
adducts (3db and 3eb) in high yields without decarbonylation
and β-hydrogen elimination (entries 9 and 12). As mentioned
above, the use of other ligands with similar steric and/or
electric natures such as PCy3, PCy2Ph, PCy2(o-biphenyl),
XPhos, and RuPhos resulted in lower yields of 3db (entries
4−8). In dioxane and 1,2-dichloroethane, the product 3db was
obtained in 84% and 72% yields, respectively, while the reaction
did not proceed in N,N-dimethylacetoamide and acetonitrile
under conditions identical to those of entry 9.
c
as an internal standard. Z/E ratio was determined by GC analysis.
d
[IrCl(cod)(IPr)] (0.025 mmol, 5.0 mol %) was used as the catalyst at
e
90 °C. Yield of isolated product.
(2a) was carried out employing various ligands with a catalytic
amount of [IrCl(cod)]2. Using PPh3 as a ligand, the desired
adduct (3aa) was afforded only in 6% yield in refluxing
toluene (entry 1). Tricyclohexylphosphine (PCy3: Cy =
cyclohexyl) afforded 3aa in moderate (53%) yield, but with
a considerable amount (12%) of the decarbonylated product
(4aa) (entry 2). Other phosphine ligands such as PCy2-
(o-Tol),20 PCy2(o-biphenyl), and XPhos21 (Figure 1) gave
Figure 1. Structures of ligands.
mixtures of 3aa and 4aa in low yields (entries 3−5). As for
NHC ligands, IMes generated in situ from IMes·HCl and
t-BuOK provided 3aa and 4aa in 37% and 4% yields,
respectively (entry 6). Gratifyingly, IPr generated from IPr·HCl
and t-BuOK is much more effective to afford 3aa selectively in
88% yield (entry 7). By the use of an isolated iridium−NHC
complex, [IrCl(cod)(IPr)],22 3aa was obtained more effectively
Various aliphatic acid chlorides were reacted with 2b in the
presence of the [IrCl(cod)]2/PCy2(o-Tol) catalyst system23
(Table 4). Acid chlorides (1f−l) in entries 1−7 afforded the
corresponding β-chloro-α,β-unsaturated ketones 3 in high
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a
Table 3. Effect of Ligands on the Iridium-Catalyzed Addition
of Stearoyl Chloride (1d) and Phenylacetyl Chloride (1e) to
Cyclohexylacetylene (2b)
Table 4. Addition of Aliphatic Acid Chlorides (1) to 2b
a
b
% yield
entry
1
ligand
3
5
c
d
1
2
1d
[IrCl(cod)(IPr)]
3db
(29)
IMes·HCl/t-BuOK
PPh3
trace
0
32
21
20
29
24
25
34
6
3
4
PCy3
37
13
16
31
5
PCy2Ph
6
PCy2(o-biphenyl)
XPhos
7
8
RuPhos
0
d
9
PCy2(o-Tol)
94 (75)
c
d
10
11
1e
[IrCl(cod)(IPr)]
3eb
(18)
RuPhos
a complex
mixture
d
12
PCy2(o-Tol)
(89)
a
Conditions: 1d or 1e (0.50 mmol), 2b (0.75 mmol), [IrCl(cod)]2
(0.0125 mmol), ligand (0.025 mmol, P/Ir = 1.0), toluene (1.0 mL), at
b
60 °C, for 20 h. Determined by GC analysis by using tetradecane as
c
an internal standard. Z/E = >99/1. [IrCl(cod)(IPr)] (0.025 mmol)
d
was used as the catalyst at 90 °C. Isolated yields in parentheses.
yields. In particular, 1h−j (entries 3−5) and 1k−l (entries 6
and 7) would afford thermodynamically stable disubstituted
alkenes and conjugated alkenes, respectively, after β-hydrogen
elimination. However, even in these cases, the desired adducts
(3hb−lb) were obtained selectively. Moreover, for arylacetyl
chlorides (1m−t), the same [IrCl(cod)]2/PCy2(o-Tol) catalyst
system also showed high catalytic activity as observed for
phenylacetyl chloride (1e) (entry 12, Table 3). The arylacetyl
chlorides having electron-rich phenyl (1m−n), electron-poor
phenyl (1o−q), 1-naphthyl (1r), 3-thienyl (1s), and diphenyl
(1t) moieties afforded 3mb−tb in good to high yields (entries
8−15). Phenoxyacetyl chloride (1u) also afforded 3ub in 82%
yield (entry 16). The Z-configuration of 3tb was further
confirmed through single-crystal X-ray diffraction.24 Unfortu-
nately, bulky acid chlorides such as pivaloyl chloride and
1-adamantanecarbonyl chloride did not react at all under the
present reaction conditions.
Next, various terminal alkynes (2) were reacted with 1k as a
representative aliphatic acid chloride at 60 °C, and the
corresponding adducts (3) were isolated in high yields regio-
and stereoselectively (Table 5). 1-Octyne (2c) and 3,3-
dimethyl-1-butyne (2d) smoothly provided 3kc and 3kd in
high yields without decarbonylation and β-hydrogen elimi-
nation (entries 1 and 2). Functionalities such as chloro, ester,
and phthalimide can be tolerated in the reaction, and the
adducts (3ke−kh) were afforded in good yields (entries 3−6).
The addition to enyne 2i successfully proceeded to give 3ki in
80% yield (entry 7). Phenylacetylene (2a) and its derivatives
(2j−n) also gave the adducts at 90 °C (entries 8−13).
Unfortunately, in all of the addition reactions of both the
aliphatic acid chlorides and aroyl chlorides, internal alkynes
showed very low reactivity and did not provide any of the cor-
responding product 3.
a
Conditions: Acid chlorides (1, 0.50 mmol), 2b (0.75 mmol),
[IrCl(cod)]2 (0.0125 mmol, 2.5 mol %), PCy2(o-Tol) (0.025 mmol,
b
c
5.0 mol %), toluene (1.0 mL), at 60 °C, for 20 h. Isolated yields. At
90 °C.
The products of the addition reaction, β-chloro-α,β-
unsaturated ketones 3, are versatile intermediates in organic
synthesis.14 As was previously reported,18 3 obtained from
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a
Table 5. Iridium-Catalyzed Addition of 1k to Terminal
Alkynes (2)
Scheme 2. Transformation of β-Chloroalkenyl Ketone 3ka
a
a
Conditions: (a) i-PrNH2 (20 equiv), Et2O, room temperature, 16 h.
(b) N2H4·H2O (3 equiv), EtOH, reflux, 5 h. (c) p-Tolylboronic acid
(1.5 equiv), Pd(OAc)2 (2.0 mol %), SPhos (5.0 mol %), K3PO4
(2.0 equiv), toluene, 100 °C, 18 h. (d) trans-Styrylboronic acid
(1.5 equiv), Pd(OAc)2 (2.0 mol %), SPhos (5.0 mol %), K3PO4 (2.0 equiv),
toluene, 100 °C, 18 h.
was converted to afford 3aa in 52% yield (eq 1). Thus,
oxidative addition of an acid chloride smoothly proceeds in the
presence of an alkyne, and then a fast insertion of the alkyne
affords 3 without decarbonylation.
In a similar stoichiometric reaction of an aliphatic acid
chloride 1d with [IrCl(cod)]2/PCy2(o-Tol) (Ir/P/1d = 1/1/1)
at 60 °C for 2 h, 1d was converted completely even in the
absence of an alkyne (entry 1, Table 6). In the reaction, 5 was
Table 6. Stoichiometric Reaction of [IrCl(cod)]2/Phosphine
a
(Phosphine = PCy2(o-Tol) or PPh3) with 1d
2b
[IrCl(cod)] + phosphine + 1d ⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯→⎯ 5 + 3db
2
toluene at 60 °C, for 2 h
c
% yield
b
entry
phosphine
2b/1d
5
3db
1
2
PCy2(o-Tol)
0
1
90
67
45
28
23
19
68
77
76
75
0
12
25
37
43
43
0
3
2
a
4
4
Conditions: 1k (0.50 mmol), 2 (0.75 mmol), [IrCl(cod)]2 (0.0125 mmol,
5
8
2.5 mol %), PCy2(o-Tol) (0.025 mmol, 5.0 mol %), toluene (1.0 mL),
b
c
6
12
0
at 60 °C, for 20 h. Isolated yields. At 90 °C.
7
PPh3
8
1
0
alkynes bearing methylene unit adjacent to C−C triple bond
affords furans.25,26 The synthetic utility of 3 was further
demonstrated by using 3ka in Scheme 2. The reaction with
isopropylamine and hydrazine cleanly gave the β-amino-α,β-
unsaturated ketone 6 and the pyrazole 7, respectively, via a
conjugated substitution reaction.27 The chloro functionality of
3ka was able to be utilized by the palladium-catalyzed Suzuki−
Miyaura coupling reaction28 with p-tolylboronic acid to give 8
in 90% yield, containing a small amount of stereoisomers
determined by NMR (Z/E = 93/7). A similar coupling reaction
with trans-styrylboronic acid gave a dienyl ketone 9 as a single
isomer in 67% yield.
To gain insight into the reaction mechanisms, stoichiometric
reactions of an acid chloride with the most active catalysts,
[IrCl(cod)(IPr)] and [IrCl(cod)]2/PCy2(o-Tol), were carried
out. First, in a stoichiometric reaction of [IrCl(cod)(IPr)] with
an aroyl chloride 1a, most 1a (>91% by GC) remained
unchanged even at 90 °C for 4 h.18 However, when an alkyne
2a was further added into the reaction mixture, most of the 1a
9
4
0
10
8
0
a
Conditions: [IrCl(cod)] (25 μmol), PCy2(o-Tol) or PPh3 (50 μmol),
b
1d (50 μmol), toluene (1.0 mL), at 60 °C, for 2 h. Molar ratios of
2b/1d. Determined by GC analysis.
c
obtained in 90% yield via decarbonylation and subsequent facile
β-hydrogen elimination. From the reaction mixture, no discrete
Ir complexes could be isolated. Quite interestingly, when the
reaction was carried out in the presence of 2b, the adduct 3db
was obtained in higher yields as the amount of 2b increased
(entries 2−6). In sharp contrast, employing PPh3 as the ligand
did not afford 3db at all and β-hydrogen elimination to 5 was pre-
vailing, even when 2b was used in excess (entries 7−10). This ligand
effect is very reminiscent of the catalytic reaction: PCy2(o-Tol)
was an excellent ligand to afford 3db in high yield, while PPh3 as
the ligand did not provide 3db at all (entries 3 and 9 in Table 3).
Unlike 1d, the stoichiometric reaction of phenylacetyl
chloride (1e) with [IrCl(cod)]2/PCy2(o-Tol) will not undergo
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β-hydrogen elimination after decarbonylation, because the
resulting species B has no β-hydrogens (Scheme 1). Actually, in
the reaction at 60 °C, a binuclear (benzyl)(carbonyl)iridium
complex 10 was isolated in 90% yield (eq 2). The structure of
10 was confirmed by X-ray diffraction study (Figure 2).24 Here,
affords adducts A (step a). For successful insertion of alkynes
(2) to afford alkenyl intermediates (D)29 without decarbon-
ylation, an appropriate ligand is crucial on the iridium center.
For aroyl derivatives of A, an IPr ligand is most suitable (entries
7 and 8 in Table 1; Table 2), while for A from aliphatic acid
chlorides PCy2(o-Tol) is requisite (entries 9 and 12 in Table 3;
Tables 4 and 5). Fast reductive elimination of D then provides
β-chloro-α,β-unsaturated ketones 3, and the catalytic cycle is
closed to regenerate the catalytic species.
As shown in eq 1, oxidative addition of aroyl chlorides to
[Ir]L (L = IPr) (step a) occurs in the presence of alkynes 2.
Insertion of 2 to A (step b) is much faster than decarbonylation
(step d). On the other hand, as indicated in eq 2, oxidative
addition of aliphatic acid chlorides occurs in the absence of 2,
but the adduct A could not be isolated due to fast
decarbonylation (step d) followed by facile β-hydrogen
elimination (step e). Here, PCy2(o-Tol) is a unique ligand
under the catalytic conditions (in the presence of excess 2). As
indicated by entries 1−6 in Table 6, PCy2(o-Tol) ligand
enhances insertion of 2 (step b) more efficiently than
decarbonylation (step d). Other ligands such as PPh3 do not
have such ability, and decarbonylation followed by β-hydrogen
elimination proceeded considerably. Thus, in the present
iridium-catalyzed reaction, the ligand with good coordination
ability and suitable steric bulk is indispensable for the selective
addition of 1 to 2.
Figure 2. Crystal structure of 10.
decarbonylation was still fast, and the corresponding phenylacetyl
complex was not obtained. However, under the catalytic conditions
(with excess alkyne), 10 catalyzed the addition of 1e to 2b to
provide 3eb without decarbonylation in 55% yield (eq 3).
CONCLUSION
■
Various aroyl chlorides and aliphatic acid chlorides (1) are
successfully added to terminal alkynes (2) to afford useful (Z)-
β-chloro-alkenyl ketones (3) regio- and stereoselectively in the
presence of a catalytic amount of iridium complexes, [IrCl-
(cod)(IPr)] or [IrCl(cod)]2/PCy2(o-Tol). The present cata-
lytic addition reaction proceeds smoothly with suppression of
undesired decarbonylation and β-hydrogen elimination. The
ligands in the catalytic system play a key role in determining the
selectivity of the addition reaction.
EXPERIMENTAL SECTION
■
Instrumentation and Chemicals. All manipulations were
performed under an argon atmosphere using standard Schlenk-type
glasswares on a dual-manifold Schlenk line. Unless otherwise noted,
materials obtained from commercial supplier were used without
further purification. Acid chlorides 1q, 1r, and 1s were prepared from
the corresponding carboxylic acid and thionyl chloride,30 and purified
by distillation under vacuum. All solvents were dried and purified by
usual procedures.31 1H, 13C, and 31P NMR spectra were measured with
Scheme 3. Plausible Reaction Mechanism
1
a JEOL ECX-400P spectrometer. The H NMR chemical shifts are
reported relative to tetramethylsilane (TMS, 0.00 ppm). The 13C
NMR chemical shifts are reported relative to CDCl3 (77.0 ppm). IR
spectra were obtained on a SHIMADZU FTIR-8300 spectrometer. EI-
MS was recorded on a SHIMADZU GCMS-QP5050A with a direct
inlet. High-resolution mass spectra (ESI-HRMS) were obtained with a
JEOL SX-102A spectrometer. Elemental analysis was carried out at the
Center for Organic Elemental Microanalysis, Graduate School of
Pharmaceutical Science, Kyoto University. GC analysis was carried out
using a Shimadzu GC-17A equipped with an integrator (C-R8A) with
a capillary column (CBP-5, 0.25 mm i.d. × 25 m). Melting points were
measured on a Yanako MP-J3 apparatus. Column chromatography was
carried out on silica gel (Kanto N60, spherical, neutral, 63−210 μm).
TLC analyses were performed on commercial glass plates bearing a
0.25 mm layer of Merck Silica gel 60F254.
With these results obtained in eqs 1−3 and Table 6, a
possible catalytic cycle is shown in Scheme 3. Oxidative
addition of acid chlorides (1) to an active catalyst species [Ir]L
General Procedure of the Addition of Aroyl Chlorides (1) to
Terminal Alkynes (2) without Decarbonylation (Table 2).
IrCl(cod)(IPr) (18 mg, 0.025 mmol) was added to a 10 mL Schlenk
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flask with a reflux condenser. The flask was evacuated and backfilled
with argon three times. A degassed toluene (1.0 mL) was then added
to the flask. An aroyl chloride (1) (0.50 mmol) and a terminal alkyne
(2) (0.75 mmol) were added to the flask, and the mixture was stirred
at 90 °C for 20 h under an argon atmosphere. After being cooled to
room temperature, the mixture was evaporated, and the product (3)
was isolated by silica gel column chromatography.
General Procedure of the Addition of Aliphatic Acid
Chlorides (1) to Terminal Alkynes (2) (Tables 4 and 5).
[IrCl(cod)]2 (8.4 mg, 0.0125 mmol) and PCy2(o-Tol) (7.2 mg,
0.025 mmol) were added to a 10 mL Schlenk flask with a reflux
condenser and a magnetic stir bar. The flask was evacuated and
backfilled with argon three times. Toluene (1.0 mL) was then added to
the flask, and the resultant solution was stirred at room temperature
for 10 min. An aliphatic acid chloride (1) (0.50 mmol) and an alkyne
(2) (0.75 mmol) were added to the flask, and the mixture was stirred
at 60 °C for 20 h under an argon atmosphere. After being cooled to
room temperature, the mixture was evaporated, and the product (3)
was isolated by silica gel column chromatography.
Stoichiometric Reaction in Table 6. [IrCl(cod)]2 (17 mg,
0.025 mmol) and PCy2(o-Tol) (14 mg, 0.050 mmol) were added to a 10 mL
Schlenk flask with a reflux condenser and a magnetic stir bar. The flask
was evacuated and backfilled with argon three times. Toluene (1.0 mL)
was then added to the flask, and the resultant solution was stirred
at room temperature for 10 min. Next, 1d (0.050 mmol) and 2b
(0, 0.050, 0.10, 0.20, 0.40, or 0.60 mmol: 2b/1d = 0, 1, 2, 4, 8, or 12)
and tetradecane (0.050 mmol) as an internal standard were added to
the flask, and the mixture was stirred at 60 °C for 2 h under an argon
atmosphere. After being cooled to room temperature, the reaction
mixture was diluted with diethyl ether (2.0 mL), and the yields of 3db
and 1-heptadecene (5) were determined by GC analysis.
Stoichiometric Reaction in Equation 1. To a 10 mL Schlenk
flask with a reflux condenser was added IrCl(cod)(IPr) (36 mg,
0.050 mmol). The flask was evacuated and backfilled with argon three
times. A degassed toluene (1.0 mL) was then added to the flask, and
the resultant solution was stirred at room temperature for 10 min. 1a
(5.8 μL, 0.050 mmol) and tridecane (25 μL, 0.10 mmol) as an internal
standard were added to the flask, and the mixture was heated at 90 °C
for 4 h under an argon atmosphere. A small aliquot (0.01 mL) was
taken out from the reaction mixture, and the samples were diluted
with diethyl ether (0.02 mL) and analyzed by GC. Subsequently, 2a
(8.2 μL, 0.075 mmol) was added to the reaction mixture, and the
reaction was carried out at 90 °C for 18 h. After being cooled to room
temperature, the reaction mixture was diluted with diethyl ether (2.0 mL).
GC analysis showed 3aa was obtained in 52% yield.
Present Address
†Department of Chemistry, Faculty of Science, Hokkaido
University, Japan.
ACKNOWLEDGMENTS
■
This work was supported by a Grant-in-Aid for Scientific
Research on Innovative Areas (“Organic synthesis based on
reaction integration” and “Molecular activation directed toward
straightforward synthesis”) from MEXT, Japan, and in part by
the Mitsubishi Foundation. T.I. is grateful for a Research
Fellowship of JSPS for Young Scientists. T.F. acknowledges the
The Naito Foundation Natural Science Scholarship.
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Stoichiometric Reaction in Equation 2. [IrCl(cod)]2 (34 mg,
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ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental procedures and characterization of the products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
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AUTHOR INFORMATION
■
Corresponding Author
ytsuji@scl.kyoto-u.ac.jp
1273
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Journal of the American Chemical Society
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