Microwave irradiated Pd-catalyzed C(sp)-H activation and cross-coupling with styryltrifluoroborates

Article abstract of DOI:10.1016/j.tetlet.2015.01.107

Effective catalytic effect of PdCl₂(d^tbpf) on the C-H activation of alkynes and its ability to overcome the limitations of styryltrifluoroborates in cross-coupling reactions by avoiding the effects of the C-X bond on starting materia

Full text of DOI:10.1016/j.tetlet.2015.01.107

Accepted Manuscript
Microwave irradiated Pd-catalyzed C(sp)-H activation and cross-coupling with
styryltrifluoroborates
Mohammad Al-Masum, Wejdan Shaban
PII:
S0040-4039(15)00134-3
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.01.107
TETL 45777
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
5 January 2015
13 January 2015
17 January 2015
Please cite this article as: Al-Masum, M., Shaban, W., Microwave irradiated Pd-catalyzed C(sp)-H activation and
cross-coupling with styryltrifluoroborates, Tetrahedron Letters (2015), doi: http://dx.doi.org/10.1016/j.tetlet.
2015.01.107
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Microwave irradiated Pd-catalyzed C(sp)-H activation
and cross-coupling with styryltrifluoroborates
Mohammad Al-Masum*, Wejdan Shaban
Effective catalytic effect of PdCl2(dtbpf) in cross-coupling reaction
of alkynes and potassium styryltrifluoroborates under microwave
heating is developed.

Microwave irradiated Pd-catalyzed C(sp)-H activation and cross-coupling with
styryltrifluoroborates
Mohammad Al-Masum*, Wejdan Shaban
Department of Chemistry, Tennessee State University, 3500 John A Merritt Blvd. Nashville, TN 37209
malmasum@tnstate.edu
Abstract: Effective catalytic effect of PdCl2(dtbpf) in the C-H activation of alkynes and its ability to overcome
the limitations of styryltrifluoroborates in cross-coupling reactions by avoiding the effects of the C-X bond in
starting materials is developed.
Keywords: C-H activation, styryltrifluoroborates, microwave, minute reaction
The fundamentals of cross-coupling chemistry for carbon-carbon bond formation reactions by potassium
organotrifluoroborates have been well explained. Coupling partners, C-X (X= I, Br, Cl, OTf, ONf, OTs), are
required to initiate the oxidative addition of Pd(0) to Pd(II) species of the catalytic cycle and furnish the
product.1 Direct activation of C-H bond will improve this valuable process by avoiding the presence of C-X in
the starting material, an approach that is gaining attention in cross-coupling chemistry.2 However, direct
activation of C-H bond by a transition metal catalyst and cross-coupling with styryltrifluoroborates has not yet
been fully explored. Developing new methods for conjugated enynes by the C-H activation of terminal alkynes
and cross-coupling with potassium organotrifluoroborates is of particular interest because of the vital role they
play in a wide range of industrial intermediates, pharmaceuticals, agro-chemicals, and molecular materials.3
Also, microwave energy has been shown to offer significant benefits in organic synthesis, providing to be a
valuable and reliable tool for organic chemists.4 In this report, we describe the microwave irradiated palladium-
catalyzed cross-coupling minute reaction of styryltrifluoroborates and C(sp)-H species (Scheme 1).

We selected phenyl acetylene (1b), as the C-H source because of it high reactivity in Sonogashira type
coupling reactions5 and ran the cross-coupling reaction of 1b with potassium 4-chloro-(2-phenylvinyl)
trifluoroborate (2e). Initially all attempts failed to yield the predicted cross-coupling product. Homocoupling of
the phenyl acetylene was observed in GC-MS analysis. To find an effective catalyst system other palladium
complexes and other active reagents choices were examined (Scheme 2). Recently, PdCl2(dtbpf) complex has
been successfully employed as a catalyst in various organic transformations involving potassium
organotrifluoroborates.6 The higher dihedral angle of P-Pd-P in PdCl2(dtbpf) improves its effectiveness as a
catalyst.7 Of the many other available complexes, this Pd-complex demonstrates the foremost catalytic effect for
the C-H activation of alkynes cross-coupled with styryltrifluoroborates. The results from this new process for
the synthesis of conjugated enynes are summarized in Table 1.

Many control experiments were run to optimize the reaction conditions and the best condition was one
equivalent of styryltrifluoroborates and one equivalent of alkyne. The procedure of forming conjugated enyne
3e from phenyl acetylene (1b) and 4-chloro-(2-phenylvinyl) trifluoroborate (2e) is a representative one. The
reaction was completed in 0.5 mmol scale. After purging with argon a microwave reaction tube with stirrer bar
was loaded with 135.5 mg (0.5 mmol, 90% pure) styryltrifluoroborate (2e), 207.0 mg (1.5 mmol) of potassium
carbonate, and 4.0 mg (0.00625 mmol) of PdCl2(dtbpf). The reaction tube was then capped and flushed with
argon following which 0.056 mL (0.5 mmol) of phenyl acetylene ( 98 % pure) and 2.5 mL of 1,4-dioxane were
added. The resulting reaction mixture was then irradiated at 140 0C for 20 min in a microwave (300 W). Crude
reaction product was filtered through celite with dichloromethane as eluent. For purification the concentrated
crude product was subjected to preparative TLC using hexane/ethyl acetate (100/1) as eluent and collected,
yielding 84.0 mg (70%) pure product. Each entry of Table 1 was run at least 2 times. The cross-coupled
conjugated enyne products are reactive molecules; therefore, chance of decomposition or oligomerization is
high.8 The crude product was subjected to silica gel chromatography for purification but unexpectedly, this
shown less effective for separation as well as promoting decomposition. When we applied ethyl propiolate (1a),
phenyl acetylene (1b), 4-trifluoromethoxyphenyl acetylene (1c), and methyl propiolate (1d) as C-H alkynes
with styryltrifluoroborates, reactions ran for 20 min and furnished the corresponding cross-coupled conjugated
enynes in good yields (Entries 1-7, Table 1). Homo-coupling minor products were also observed in GC-MS. In
the case of trimethylsilyl acetylene (1e), reaction mixtures were microwaved for 60 min to optimize results. In
all cases, E:Z mixtures (60:40 ratio) were obtained (Entries 8, 9, and 10, Table 1). Although our focus is to
explore the reactivity of potassium styryltrifluoroborates, we verified arylvinylboronic acids as boron reagents
with C-H alkynes for the same type of cross-coupling reactions.9 When 1.0 mmol of 4-Chloro-(2-phenylvinyl)
boronic acid (2e) was reacted with 0.5 mmol of ethyl propiolate (1a), phenyl acetylene (1b), and methyl
propiolate (1d) under same reaction conditions, all exhibited the corresponding clean cross-coupling reaction
products in GC-MS. Equimolar amounts of boronic acid and alkyne worked but the best result occurred when 2
equiv of boronic acid were loaded.

Table 1. Cross-coupling reactions of alkynes and styryltrifluoroborates. a
Yield %
Entry
Alkynes 1
Cross-coupled Enynes 3
StyrylBF3K 2
CO2Et
BF3K
BF3K
1
84
H
CO2Et
3a
3b
1a
2a
CO2Et
CO2Et
82
69
2
3
H
CO2Et
Cl
Cl
1a
2b
BF3K
H
CO2Et
F3C
F3C
1a
2c
2a
3c
Ph
Ph
BF3K
BF3K
4
5
67
70
H
Ph
3d
3e
1b
1b
H
Ph
Cl
Cl
2b
2a
OCF3
OCF3
BF3K
BF3K
83
70
6
7
3f
1c
CO2Me
H
H
CO2Me
1d
2a
3g
Cl
SiMe3
SiMe3
BF3K
BF3K
75b
82b
8
9
SiMe3
1e
3h
2d
Me
Me
H
SiMe3
1e
3i
3j
2e
2b
F
F
SiMe3
BF3K
72b
H
SiMe3
1e
10
Cl
Cl
aAll reactions were repeated at least 2 times, Reaction scale (0.5 mmol), PdCl2(dtbpf)[1.25 mol %], Reaction
b
:
E
Z
ratio (60:40)
time 20 min except Entries 8,9,10 (1 h). Yields (Isolated by Prep TLC technique).

Scheme 3
PdCl2(dtbpf)
K2CO3
Pd(0)
H
R'
1
R'
OA
Z
3
H PdII
R'
RE
TM
PdII
BF3K
+
K2CO3
2
Z
Z
R'
Inorganic byproducts
This new result further demonstrates the effective catalytic effect of PdCl2(dtbpf) in the C-H activation of
alkynes and its ability to overcome the limitations of styryltrifluoroborates in cross-coupling reactions by
avoiding the effects of the C-X bond in starting materials. In our consideration, PdCl2(dtbpf) catalyst may
convert to Pd(0) by potassium carbonate and acting as active catalyst by forming PdII species after oxidative
addition, which then undergoes transmetallation followed by reductive elimination, and thereby forming the
desired cross-coupling product. The probable catalytic cycle is shown in Scheme 3.
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