Copper-catalyzed cross- and carbonylative coupling reactions of alkynyliodonium salts with organoboronic acids and organostannanes

Article abstract of DOI:10.1055/s-2005-918934

Copper-catalyzed cross- and carbonylative coupling reactions have been achieved in the reaction of a variety of alkynyliodonium salts with arylboronic acids and organostannanes under the mild reaction conditions in high yield. Our investigation shows that the alkynylidonium tetrafluoroborates are more efficient than those of triflates and tosylates. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-918934

LETTER
2631
Copper-Catalyzed Cross- and Carbonylative Coupling Reactions of
Alkynyliodonium Salts with Organoboronic Acids and Organostannanes
Cross-Coupling R
h
eactions of
a
A
lkynyliod
n
onium Salts -Mo Yu,* Jae-Hong Kweon, Pil-Su Ho, Sin-Cheol Kang, Gong Yeal Lee
Department of Chemistry and Institute of Basic Sciences, Sungkyunkwan University, Suwon 440-746, Korea
Fax +82(31)2907075; E-mail: cmyu@chem.skku.ac.kr
Received 18 July 2005
alkynyliodonium salts with alkenyl- and aryl boronic
acids and stannanes which would expand the utility and
practicability mainly due to the availability of reagents.
This research led to the discovery of efficient reaction
Abstract: Copper-catalyzed cross- and carbonylative coupling
reactions have been achieved in the reaction of a variety of alkynyl-
iodonium salts with arylboronic acids and organostannanes under
the mild reaction conditions in high yield. Our investigation shows
that the alkynylidonium tetrafluoroborates are more efficient than routes in the production of a variety of disubstituted
those of triflates and tosylates.
alkynes and alkynyl ketones through a copper-catalyzed
couplings as well as a carbonylative coupling under mild
reaction conditions.
Key words: copper catalyst, iodonium salt, organoboronic acid,
coupling, organostannane
CuX'
R2B(OH)2
+
R1
I+Ph X–
R1
R2
conditions
The copper-catalyzed or mediated organic reactions in-
cluding coupling reaction have been regarded as one of
the useful and efficient methods in organic synthesis.1
Cross-coupling reactions of a terminal alkyne with a
variety of alkenyl and aryl reagents have been intensively
investigated over last 20 years, providing their worth as an
important tool for the synthesis of functional substances
including pharmaceuticals and advanced materials.2 The
most significant contribution to this coupling between ter-
minal alkynes and aryl moieties was the introduction of
palladium catalyst involving the use of copper(I) with
amine base known as the Sonogashira reaction.3 This
basic procedure is currently the commonly used method
for alkyne coupling and led to the modification of a
variety of reagents for the new conditions to realize
practicability.4 Even though the cross-coupling reaction
between alkynylcopper and aryl halides in the presence of
pyridine was developed by Stephens and Castro earlier
than the Sonogashira procedure, the Castro–Stephens
reaction has relatively little attentions mainly due to the
use of stoichiometric amounts of copper(I) with the harsh
reaction conditions.5 Although the copper-mediated
alkyne–alkyne cross-coupling reaction, known as the
Cadiot–Chodkiewick reaction, of bromoalkyne with
alkyne in the presence of NH2OH as a base under the mild
reaction conditions to provide a dialkyne has been re-
ported,6 CuI·2PPh3 catalyzed coupling of aryl- and vinyl
iodides with terminal alkynes required the high tempera-
ture and longer reaction time.7 Recently, the copper-
catalyzed cross-coupling of terminal alkynes with hyper-
valent aryl- and alkenyliodonium salts has been investi-
gated in our laboratory.8 The efficiency of this protocol in
terms of reactivity carried out at room temperature
encouraged us to develop a method for the coupling of
1
2
3
X
– = OTf, OTs, BF4
Scheme 1
The first study for preliminary experiments focused on the
feasibility of alkynyliodonium salts 1 for the copper-cata-
lyzed cross-coupling with boronic acid 2 as described in
Scheme 1. To find optimum conditions a series of experi-
ments has been performed with several alkynyliodonium
salts such as triflate, tosylate and tetrafluoroborate.9 Initial
attempts of the coupling reaction of 1 (R1 = Bu, X– = OTf)
with PhB(OH)2 (2a) and K2CO3 in the presence of CuI (10
mol%) under various conditions afforded encouraging but
marginal results. Although product 3a was produced
during the reactions (3 h at 20 °C in 4:1 DME–H2O) in ca
50% yield, the decomposition of reagent and low yield
remained to be solved. Fortunately, we were delighted to
find that the alkynyliodonium tetrafluoroborate 1 (X– =
BF4) could be a proper reagent;10 this was generally supe-
rior to those of triflate and tosylate and chosen for system-
atic studies. After surveying numerous conditions for
orienting experiments, several key findings emerged: i) 5
mol% of CuI required for optimal conditions in terms of
chemical yields and reaction rates; ii) CuI tuned out to be
most effective catalyst compared to other copper species
such as CuCl, CuCN, and CuOAc (less than 10% yield);
iii) the use of K2CO3 was much more effective than
Na2CO3 and Cs2CO3; iv) reaction performed at 20 °C in
DME–DMF–H2O (3:1:1) resulted in the best chemical
yields in comparison with other solvents such as DME,
DMF, THF, and MeCN. Under optimal conditions, the
reaction was performed by addition of 1a (1 equiv) to a
solution of phenylboronic acid (2a, 1.1 equiv) and CuI
(0.05 equiv) in the presence of K2CO3 (1.2 equiv) in
DME–DMF–H2O (3:1:1) at 20 °C. After one hour at
20 °C, the reaction was quenched by addition of aqueous
SYNLETT 2005, No. 17, pp 2631–2634
1
7
.1
0
.2
0
0
5
Advanced online publication: 05.10.2005
DOI: 10.1055/s-2005-918934; Art ID: U23005ST
© Georg Thieme Verlag Stuttgart · New York

2632
C.-M. Yu et al.
LETTER
Table 1 Coupling Reaction of 1 with 2 to 3 Catalyzed by CuI
NH4Cl. The crude product was purified by SiO2 column
chromatography to give 3a in 91% yield.11 With the
notion that this approach might lead to a general and effi-
cient method for the coupling reaction, we set out to deter-
mine the scope of reaction as listed in Table 1. Indeed, the
method is successful with a variety of 1 and 2 to yield the
disubstituted alkynes 3 within one hour in high yields as it
can be seen in Table 1.
CuI (5 mol%)
+ R2B(OH)2
R1
R2
R1
I+PhBF4
–
1
2
3
conditions: K2CO3 (1.2 equiv), DME/DMF/H2O (3:1:1), 20 °C, 1 h
Entry
1
1 (R1)
Bu 1a
2 (R2)
Product
Yield (%)a
91
3a
Table 2 Coupling Reaction of 1 with 4 to 3 Catalyzed by CuI
2a
CuI (5 mol%)
R1
I+PhBF4
R2SnBu3
–
+
R1
R2
2
3
Bu 1a
Bu 1a
3b
3d
78
87
1
4
3
MeO
conditions: DME/H2O (4:1), 20 °C, 3 h
2b
Entry
1
1 (R1)
Bu 1a
2 (R2)
Product Yield (%)
3a
81
Cl
Cl
4a
2c
2
3
Bu 1a
Ph 1c
3g
3k
71
75
4
5
Bu 1a
Bu 1a
3e
3f
71
74
Ph
4c
S
2d
4a
O
2e
4
5
6
Ph 1c
3l
77
68
66
MeO
6
7
Bu 1a
3g
3h
77
85
Ph
4b
2f
Me3Si 1d
Me3Si 1d
3n
3o
t-Bu 1b
4a
2a
8
9
t-Bu 1b
t-Bu 1b
3i
3j
84
81
MeO
O
4d
2b
In order to extend the scope of reaction, a coupling
reaction of the alkynyliodonium reagent 1 with organo-
stannanes 4 under similar conditions to those described
above was also investigated mainly due to the availability
of tin compounds.12 Reaction of 1a (1 equiv) with 4a (1.2
equiv) in the presence of CuI (5 mol%) in DME–H2O
(4:1) at 20 °C for three hours afforded 3a in 81% isolated
yield. The data summarized in Table 2 allow the follow-
ing points to be stated: 1) reaction was usually complete
within three hours; 2) in general, the coupling reaction
provided modest to good isolated yields, which are some-
what lower than the results appeared in Table 1.
Cl
Cl
2c
10
11
12
Ph 1c
Ph 1c
Ph 1c
3k
3l
78
88
71
2a
MeO
2b
3m
With our research scope of the catalytic cross-coupling
reaction of alkynyliodonium salts, we turned our attention
next to examine the application of this approach to extend
the scope to the synthesis of a,b-ynone 5 under carbon
monoxide atmosphere mainly due to a synthetic utility13
as illustrated in Table 3.14 Treatment of 1a (1 equiv) with
2a (1.1 equiv) in the presence of CuI (10 mol%) and
S
2d
a Refers to isolated product.
Synlett 2005, No. 17, 2631–2634 © Thieme Stuttgart · New York

LETTER
Cross-Coupling Reactions of Alkynyliodonium Salts
2633
Table 3 Carbonylative Coupling of 1 with 2 to 5 Catalyzed by CuI
have not been rigorously elucidated, the following path-
way could be a probable chemical route as illustrated in
Figure 1.16 Reaction of 1 with CuI could undergo the for-
mation of intermediate A via an oxidative addition. The
advantage of this process with hypervalent iodonium salts
is likely to be due to a preference of reducing power of
highly electron-deficient hypervalent iodonium salt com-
pared to normal halides. The enhanced reactivity of the
tetrafluoroborate salt favored over triflate and tosylate
may be interpreted by assuming that the non-coordinative
tetrafluoroborate in A resulted in the formation of vacancy
to accommodate boronic acid leading to B via transmetal-
lation. Reductive elimination of B led to the disubstituted
alkyne 3 along with the regeneration of copper(I) catalyst.
Under carbon monoxide atmosphere, subsequent carbon-
ylation of B to C, then migratory CO insertion followed
by reductive elimination led to the formation of a,b-
ynones 5.
O
CuI (10 mol%)
R2B(OH)2
R1
–
I+PhBF4
R1
+
CO (1 atm)
R2
1
2
5
conditions: K2CO3 (1.2 equiv), DME/H2O (4:1), 20 °C, 2 h
Entry
1
1 (R1)
Bu 1a
2 (R2)
Product Yield (%)a
5a
5b
5c
5d
5e
5f
83
74
63
77
88
72
2a
2
4
5
6
7
Bu 1a
MeO
2b
Bu 1a
O
2e
O
t-Bu 1b
t-Bu 1b
t-Bu 1b
R1
I+Ph BF4
–
R1
1
R2
5
CuI
2a
PhI
O
C
MeO
BF4
Cu(III) I
2b
R1
R1
Cu(III) I
R2
A
C
Cl
K2CO3
R2B(OH)2
Cl
2
2c
R2
CO
KOCO2B(OH)2
KBF4
8
9
Ph 1c
Ph 1c
Ph 1c
5g
5h
5i
77
79
61
R1
Cu(III) I
B
3
2a
R1
R2
MeO
2b
Figure 1
10
In summary, this paper describes an efficient procedure
for the copper-catalyzed cross-coupling of alkynyliodoni-
um tetrafluoroborates with arylboronic acids and arylstan-
nanes under mild conditions in a general and efficient
way, which promises to be widely useful. The carbonyl-
ative cross-coupling reaction was achieved under the low-
pressure carbon monoxide atmosphere. Further studies
with more versatile reagents to extend applicability of this
method are in progress.
S
2d
a Refers to isolated product.
K2CO3 (1.2 equiv) under carbon monoxide atmosphere (1
atm) in DME–H2O (4:1) at 20 °C for two hours afforded
5a in 83% isolated yield.15 As shown in Table 3, the
carbonylative cross-coupling reactions were conducted on
a variety of alkynylidonium salts and arylboronic acids
under identical conditions to furnish a,b-ynones 5 with
good yields.
Acknowledgment
Generous financial support by the Korea Science & Engineering
Foundation (R01-2005-000-10381-0) and the Center for Molecular
Design & Synthesis (CMDS: KOSEF SRC) at KAIST is gratefully
acknowledged.
Although the exact mechanistic aspects of this transfor-
mation including the effects of alkynyliodonium tetra-
fluoroborate compared to those of triflate and tosylate
Synlett 2005, No. 17, 2631–2634 © Thieme Stuttgart · New York

2634
C.-M. Yu et al.
LETTER
(11) Typical Procedure for the Synthesis of 3a.
References
A flame-dried flask containing CuI (7.6 mg, 0.04 mmol),
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and brine (1 ×). The organic layer was dried over anhyd
MgSO4, filtered, and concentrated under reduced pressure.
The crude product was purified by flash column
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concentrated under reduced pressure. The crude product was
purified by flash column chromatography (EtOAc–hexane,
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Synlett 2005, No. 17, 2631–2634 © Thieme Stuttgart · New York