Palladium-Catalyzed Carbonylative Cross-Coupling Reaction between Aryl(Heteroaryl) Iodides and Tricyclopropylbismuth: Expedient Access to Aryl Cyclopropylketones

Article abstract of DOI:10.1055/s-0036-1590832

The carbonylative cross-coupling reaction between aryl and heteroaryl iodides and tricyclopropylbismuth is reported. The reaction is catalyzed by (SIPr)Pd(allyl)Cl, a NHC-palladium(II) catalyst, operates under 1 atm of carbon monoxide and tolerates a wide range of functional groups. The use of lithium chloride was found to provide higher yields of the desired aryl cyclopropylketones. The conditions were also applied to the carbonylative cross-coupling of an iodoalkene to afford the corresponding alkenyl cyclopropylketone.

Full text of DOI:10.1055/s-0036-1590832

SYNLETT
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© Georg Thieme Verlag Stuttgart · New York
2017, 28, A–F
letter
A
en
E. Benoit et al.
Letter
Synlett
Palladium-Catalyzed Carbonylative Cross-Coupling Reaction
between Aryl(Heteroaryl) Iodides and Tricyclopropylbismuth:
Expedient Access to Aryl Cyclopropylketones
Emeline Benoit
Julien Dansereau
Bi
O
Alexandre Gagnon*
i-Pr
i-Pr
N
N
I
(1.0 to 1.5 equiv)
Het
Het
FG
FG
Département de Chimie, Université du Québec à Montréal, C.P.
8888, Succ. Centre-Ville, Montréal, Québec, H3C 3P8, Canada
gagnon.alexandre@uqam.ca
i-Pr
i-Pr
(SIPr)Pd(allyl)Cl
(5 to 10 mol%)
Na2CO3 (2.0 equiv)
LiCl (2.0 equiv)
Pd
Cl
• 15 examples
• up to 98% yield
• compatible with C(O)R,
CHO, CO2R, NO2, O2CR,
OR, OTHP, Br, CF3
(SIPr)Pd(allyl)Cl
Dedicated to Professor Victor Snieckus on the occasion of his
80th birthday
DMF, over night, 40 to 80 °C
CO (1 atm)
Received: 24.05.2017
Accepted after revision: 20.06.2017
Published online: 19.07.2017
Aryl cyclopropylketones are commonly prepared via
Lewis acid catalyzed Friedel–Crafts acylation of aromatic
substrates with cyclopropanecarbonyl chloride (Scheme 1,
A).17,21 However, to be efficient, this approach usually re-
quires electronically rich aromatic compounds. In addition,
the functional-group compatibility of this approach is usu-
ally compromised by the presence of the highly reactive
Lewis acid. The addition of aryllithium to cyclopropanecar-
bonyl chloride22 or cyclopropane carboxylic acid23 (Scheme
1, B) and cyclopropylmagnesium halide to N,N-dimethyl or
N-methyl-N-methoxy benzoyl amides (Scheme 1, C)24 has
also been sporadically utilized to access aryl cyclopropylke-
tones. In another approach, aryl cyclopropylketones were
obtained by adding cyclopropylmagnesium halides to aryl
cyanides in the presence of copper iodide (Scheme 1, D).25
The uncatalyzed addition of arylmagnesium halides4 and
the metal-catalyzed addition of potassium phenyltrifluo-
roborate26 and arylboronic acids27 onto cyclopropyl cyanide
has also been utilized to prepare aryl cyclopropylketones
(Scheme 1, E). Recently, the synthesis of aryl cyclopropylke-
tones through sequential addition of an aryllithium reagent
to carbon dioxide followed by cyclopropyllithium in flow
chemistry mode has been reported (Scheme 1, F).28 Aryl cy-
clopropanes can also be prepared via Simmons–Smith or
Corey–Chaykovsky cyclopropanation of aryl vinylketones
(Scheme 1, G).29 Although methods A–G are frequently used
to prepare aryl cyclopropylketones, they are not free of lim-
itations. In fact, many of these approaches require highly
reactive organometallic reagents which can severely limit
the nature of functional groups that can be present on the
substrate.
DOI: 10.1055/s-0036-1590832; Art ID: st-2017-r0394-l
Abstract The carbonylative cross-coupling reaction between aryl and
heteroaryl iodides and tricyclopropylbismuth is reported. The reaction
is catalyzed by (SIPr)Pd(allyl)Cl, a NHC-palladium(II) catalyst, operates
under 1 atm of carbon monoxide and tolerates a wide range of func-
tional groups. The use of lithium chloride was found to provide higher
yields of the desired aryl cyclopropylketones. The conditions were also
applied to the carbonylative cross-coupling of an iodoalkene to afford
the corresponding alkenyl cyclopropylketone.
Key words aryl cyclopropylketones, carbon monoxide, carbonylative
cross-coupling, NHC ligand, palladium, tricyclopropylbismuth
Aryl cyclopropylketones are highly versatile synthons
that can be engaged in a multitude of reactions to prepare
architecturally complex molecules. For instance, they have
been used in nickel-catalyzed [3+2] cycloadditions with
alkynes,1 nickel-catalyzed dimerization and cross reactions
with enones,2 homo-Nazarov reactions,3 magnesium chlo-
ride induced rearrangements,4 reductive ring-opening reac-
tions,5 radical ring opening/addition to aldehydes,6 Lewis
acid mediated opening/condensations to α-ketoesters,7 al-
dehydes,8 and imines,9 Lewis acid promoted reactions with
sulfonamides,10 mercuric salt promoted iodination/opening
reactions,11 nickel-catalyzed borylation reactions,12 photo-
chemical dimerization reactions,13 iodine-induced ring
opening/aldol reactions,14 and rearrangement reactions via
their arylhydrazones derivatives.15
Aryl cyclopropylketones have also been frequently used
in medicinal chemistry to prepare biologically active mole-
cules. For example, aryl cyclopropylketones can be found in
ciproxifan,16 an extremely potent histamine H3 agonist/an-
tagonist, in lead molecules with antifungal17 or antituber-
cular activities,18 in GPR120 agonists,19 and in dual ligands
for melatonin (MT1/MT2) and serotonin 5-HT2c receptors.20
The preparation of diaryl and aryl alkylketones via car-
bonylative cross-coupling reaction between aryl halides
and organometallic reagents has been extensively docu-
mented.30 Surprisingly, however, to the best of our knowl-
edge, aryl cyclopropylketones have never been prepared via
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F

B
E. Benoit et al.
Letter
Synlett
on in cross-coupling reactions,47 could provide a highly ex-
peditive route to aryl cyclopropyl ketones (Scheme 1, H).
We would like to report herein our results towards this en-
deavor.
O
O
O
A
B
c-PrC(O)Cl
Ar
H
Ar
AlCl3
c-PrC(O)X
ArLi
Ar
Ar
We began by attempting the reaction between tricyclo-
propylbismuth (2a) and 4-iodo methyl benzoate (1a) using
conditions that we reported for the carbonylative cross-
coupling reaction of triarylbismuthines with aryl iodides.45
Using 1.5 equivalents of tricyclopropylbismuth (2a), 5 mol%
of tetrakis(triphenylphosphine)palladium(0) and 2.0 equiv-
alents of rubidium carbonate in the presence of 2.0 equiva-
lents of lithium chloride in DMF at 80 °C under 1 atm of car-
bon monoxide for six hours, the desired aryl cyclopropylke-
tone 348 was obtained in a meager 26% yield along with 58%
of noncarbonylative arylcyclopropane product 4 (Table 1,
entry 1), showing that tricyclopropylbismuth is much less
reactive than triarylbismuthines under these conditions.
With the aim of improving the efficiency of the process, we
then embarked on the systematic optimization of every re-
action parameter. First, increasing the reaction time to 16
hours led to a higher but still unsatisfactory yield (Table 1,
entry 2). Among all the palladium catalysts and ligands that
were tested, allyl[1,3-bis(2,6-diisopropylphenyl)-2-imidaz-
olidinylidene]-chloropalladium(II) (SIPr)Pd(allyl)Cl provid-
ed the highest yield, affording 3 in 87% yield (Table 1, entry
3).49 Andrus demonstrated previously that palladium cata-
lysts containing this NHC ligand efficiently catalyze the car-
bonylative cross-coupling reaction of aryl diazonium ions
with arylboronic acids.50 Using conditions from entry 3, we
then tested other ‘classical’ cyclopropyl boron-based donor
reagents. Interestingly, and rather surprisingly, cycloprop-
ylboronic acid (2b), cyclopropylboronic acid pinacol ester
(2c), potassium cyclopropyltrifluoroborate (2d), and cyclo-
propylboronic acid MIDA ester (2e) gave no desired product
(Table 1, entry 4). Obviously, the use of these reagents in
this carbonylative cross-coupling reaction would require
extensive optimization of the conditions. Consequently, we
continued our journey with tricyclopropylbismuth with the
intention of reinvestigating these reagents in the future.
Since rubidium carbonate is quite expensive, we then tested
other inorganic and organic bases in order to find a cheaper
replacement (Table 1, entries 5–9). In the event, we found
that potassium carbonate, sodium carbonate, and triethyl-
amine give results comparable to rubidium carbonate. On
the contrary, lower yields were obtained with potassium
phosphate tribasic and cesium carbonate. Interestingly, the
noncarbonylative arylcyclopropane product 4 was observed
in small amount with most bases, except with cesium and
sodium carbonate. In light of sodium carbonate low cost
and its apparent ability to suppress the formation of the
undesired noncarbonylative product, we continued our op-
timization with this inorganic base. Reducing the loading of
sodium carbonate to 1.0 equivalent was found to have a
considerable negative effect on the yield of the reaction (Ta-
ble 1, entry 10). Running the reaction in acetonitrile, diox-
X = Cl, OH
O
C
MgX
Me
Ar
N
Z
Z = OMe, Me
D
E
O
MgX
CuI
Ar CN
Ar
O
ArMgX
CN
or
Ar
PhBF3K, (CF3CO2)2Pd
or
ArB(OH)2, [Ni] or [Pd]
O
O
F
1) ArLi
CO2
Ar
Ar
2) c-PrLi
O
G
Et2Zn, CH2I2
Cu(OTf)2
Ar
or
Me2S(O)CH2
H: This work
O
Bi
3
Ar(Het)
I
(Het)Ar
[Pd], CO
Scheme 1 Methods A–G: Selected methods for the synthesis of aryl
cyclopropylketones. Method H: Synthesis of aryl cyclopropylketones via
palladium-catalyzed carbonylative cross-coupling reaction between
aryl(heteroaryl) iodides and tricyclopropylbismuth.
carbonylative cross-coupling reaction. This approach would
provide an expedient route to this important class of com-
pounds.
Organobismuth compounds are organometallic re-
agents that contain a C–Bi bond.31 These compounds are
roughly divided into two classes: trivalent reagents and
pentavalent reagents where bismuth is at the +3 and +5 ox-
idation state, respectively. Triarybismuthines Ar3Bi, intro-
duced in 1887 by Michaelis and Polis,32 are air- and mois-
ture-stable and can thus be purified by simple column
chromatography. On the contrary, trialkylbismuthines R3Bi,
introduced by Dünhaupt,33 Marquardt34 and Breed35 more
than 150 years ago, are usually pyrophoric and must there-
fore be handled and purified under inert atmosphere. The
use of organobismuth compounds in organic synthesis was
greatly popularized by Barton and Finet36 in the 1980s and
more recently by Rao,37 Condon,38 and others.39
Our group reported a portfolio of methods for the con-
struction of C–C,40 C–N,41 and C–O42 bond using triaryl and
trialkyl organobismuth reagents.43 The group of Cai44 and
our group45 recently disclosed protocols for the carbonyla-
tive cross-coupling reaction of aryl iodides with triarylbis-
muthines. We envisioned that the carbonylative cross-cou-
pling reaction between aryl halides and tricyclopropylbis-
muth, a reagent that we introduced in 200746 and used later
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F

C
E. Benoit et al.
Letter
Synlett
ane, toluene, or dimethoxyethane led to a dramatic reduc-
tion in the yield of the reaction (Table 1, entries 11–14). We
then investigated the effect of lithium chloride and found a
minor erosion in the yield of the reaction upon using 1.0
equivalent of LiCl (Table 1, entry 15) or no LiCl (Table 1, en-
try 16). We also found that the efficiency of the reaction
was preserved when 1.0 equivalent of tricyclopropylbis-
muth was used in place of 1.5 equivalents (Table 1, entry
17). Reducing the loading of tricyclopropylbismuth further
to 0.5 equivalents led to a considerable drop in the yield of
the reaction, showing that the ability of the second cyclo-
propyl group to transfer is lower than the first (Table 1, en-
try 18). Optimization of the reaction temperature showed
that it could be reduced from 80 °C to 40 °C (Table 1, entry
Table 1 Optimization of the Reaction Conditions for the Palladium-Catalyzed Carbonylative Cross-Coupling Reaction between Cyclopropyl Reagents
2a–e and 4-Iodo- (1a), 4-Bromo- (1b), and 4-Triflyl (1c) Methylbenzoate
MX2Ln
O
i-Pr
N
i-Pr
2
N
X
(n equiv)
+
i-Pr
i-Pr
[Pd] (5 mol%)
base (2.0 equiv)
additive (2.0 equiv)
solvent (0.1 M)
MeO2C
Pd
MeO2C
MeO2C
Cl
3
4
1a: X = I
1b: X = Br
1c: X = OTf
(SIPr)Pd(allyl)Cl
CO (1 atm), T, t
Me
N
Cyclopropyl reagents
OH
OH
O
B
=
O
O
Bi
B
BF3K
MX2Ln
B
O
O
O
2a
2b
2c
2d
2e
Entry
1
Catalyst [Pd]
Base
Solvent
Additive
c-PrMX2Ln
(n equiv)
Temp
(°C)
Time
(h)
Yield of 3 Yield of 4 RSM 1
(%)a
(%)a
(%)b
1
2
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b,c
Pd(PPh3)4
Rb2CO3
Rb2CO3
Rb2CO3
Rb2CO3
K3PO4
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
MeCN
LiCl
LiCl
LiCl
LiCl
LiCl
LiCl
LiCl
LiCl
LiCl
LiCl
LiCl
LiCl
LiCl
LiCl
LiCld
2a (1.5)
2a (1.5)
2a (1.5)
2b–e (1.5)
2a (1.5)
2a (1.5)
2a (1.5)
2a (1.5)
2a (1.5)
2a (1.5)
2a (1.5)
2a (1.5)
2a (1.5)
2a (1.5)
2a (1.5)
2a (1.5)
2a (1.0)
2a (0.5)
2a (1.0)
2a (1.0)
2a (1.0)
2a (1.0)
2a (1.0)
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
40
r.t.
40
40
80
6
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
6
26
50
87
0
58
27
7
0
0
Pd(PPh3)4
3
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
(SIPr)Pd(allyl)Cl
0
4
0
99
0
5
67
92
76
92
99
60
49
4
2
6
K2CO3
3
0
7
Cs2CO3
Et3N
0
0
8
5
0
9
Na2CO3
0
0
c
10
11
12
13
14
15
16
17
18
19
20
21
22
23
Na2CO3
35
0
0
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
39
78
86
72
0
dioxane
toluene
DME
DMF
0
5
0
18
92
90
95
64
98
0
0
8
DMF
no additive
LiCl
6
0
DMF
0
0
DMF
LiCl
0
1
DMF
LiCl
2
0
DMF
LiCl
0
99
10
50
99
DMF
LiCl
90
50
0
0
DMF
LiCl
3
0
DMF
LiCl
16
0
a Yields of isolated pure products.
b RSM = recovered starting material.
c Na2CO3 (1.0 equiv).
d LiCl (1.0 equiv).
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F

D
E. Benoit et al.
Letter
Synlett
19) but not room temperature (Table 1, entry 20). The reac-
tion time could also be reduced to six hours with a mini-
mum impact on the yield of the reaction (Table 1, entry 21).
However, reducing the reaction time to three hours had a
dramatic impact on the yield of the reaction (Table 1, entry
22). Last, to our surprise, no reaction was observed when
the reaction was performed on aryl bromide 1b or aryl tri-
flate 1c (Table 1, entry 23).
Table 2 Palladium-Catalyzed Carbonylative Cross-Coupling Reaction
between Aryl(heteroaryl) Iodides 5 and Tricyclopropylbismuth (2a)
Bi
O
2a
(1.0 to 1.5 equiv)
+
Ar(Het)
I
(Het)Ar
Ar(Het)
(SIPr)Pd(allyl)Cl
(5 to 10 mol%)
Na2CO3, LiCl
5
7
6
Next, using the optimized reaction conditions from Ta-
ble 1, entry 19 (method A),51 we investigated the substrate
scope of the reaction (Table 2). We also performed every
entry using more ‘forcing’ conditions which involved 1.5
equivalents of tricyclopropylbismuth and 10 mol% of
(SIPr)Pd(allyl)Cl (method B)52 at 80 °C. Our studies first
demonstrated that the carbonylative cross-coupling reac-
tion can be done on aryl iodides that are para-, meta-, and
ortho-substituted (Table 2, entries 1–3) and that possess
electron-withdrawing and electron-donating groups (Table
2, entries 4 and 5). Our results also indicate that the reac-
tion tolerates a wide array of functional groups such as a
THP-protected phenol (Table 2, entry 6), a dioxolane (Table
2, entry 7), an ester (Table 2, entry 8), a methyl ketone (Ta-
ble 2, entry 9), an aldehyde (Table 2, entry 10), a pivalate
(Table 2, entry 11), and a benzyl-protected alcohol (Table 2,
entry 12). Interestingly, the reaction was also found to be
compatible with a bromide (Table 2, entry 13), thus offering
a handle for further functionalization of the product via
other palladium-catalyzed cross-coupling reactions. Het-
eroaryl iodides could also be successfully engaged in this
reaction, as shown by 2-iodothiophene (5n). It is worth
mentioning that when the yield of the desired aryl cyclo-
propylketone 6 was low using method A, substantial
amounts of unreacted starting material could often be re-
covered, accounting for almost complete mass balance in
many cases (Table 2, entries 5, 6, 11, 12). Oftentimes, the
yield of 6 could be improved by using method B (Table 2,
entries 1–3, 5–7, 11, and 12). Surprisingly, in some cases, a
reduction in the yield of the aryl cyclopropylketone was ob-
served upon using method B (Table 2, entries 4, 8–10, 13,
and 14). In those cases, the noncarbonylative cross-cou-
pling arylcyclopropane 753 was also isolated, suggesting
that higher catalyst loading favors both products 6 and 7.
Alkenyl cyclopropylketones are interesting substrates in
organic chemistry as they can be used in a variety of reac-
tions.54 The carbonylative cross-coupling reaction between
cyclopropylmetals and haloalkenes could provide an expe-
dient access to this class of compounds. To the best of our
knowledge, this approach has never been explored. To test
the transferability of our reaction conditions on alkenyl
substrates, we attempted the reaction of trans-iodoalkene 8
using method A and obtained the desired alkenyl cyclopro-
pylketone 9 in 61% yield (Scheme 2). Method B afforded the
product in a similar yield. The full scope of this reaction is
currently under investigation in our laboratory and results
will be reported in due course.
CO (1 atm), DMF
40 to 80 °C
Entry
1
(Het)Ar 5
Yield of 6 (%)a Yield of 7 (%)a RSM 5 (%)b
6a
7a
0 (A)
0 (B)
5a
46 (A)
14 (B)
14 (A)c
66 (B)d
F3C
6b
51 (A)
62 (B)
7b
0 (A)
0 (B)
5b
0 (A)
0 (B)
2
3
4
5
6
7
8
6c
26 (A)
89 (B)
7c
0 (A)
0 (B)
5c
0 (A)
0 (B)
6d
93 (A)
44 (B)
7d
0 (A)
43 (B)
5d
7 (A)
0 (B)
O2N
BnO
6e
34 (A)
54 (B)
7e
0 (A)
0 (B)
5e
65 (A)
0 (B)
6f
20 (A)
68 (B)
7f
0 (A)
0 (B)
5f
67 (A)
0 (B)
THPO
O
6g
12 (A)
57 (B)
7g
0 (A)
29 (b)
5g
61 (A)
0 (B)
O
EtO2C
6h
82 (A)
64 (B)
7h
0 (A)
21 (B)
5h
18 (A)
0 (B)
6i
62 (A)
52 (B)
7i
0 (A)
23 (B)
5i
6 (A)
23 (B)
Me
O
9
6j
92 (A)
36 (B)
7j
0 (A)
29 (B)
5j
5 (A)
0 (B)
H
O
10
11
12
6k
30 (A)
46 (B)
7k
0 (A)
0 (B)
5k
70 (A)
0 (B)
PivO
6l
17 (A)
87 (B)
7l
0 (A)
0 (B)
5l
78 (A)
11 (B)
OBn
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F

E
E. Benoit et al.
Letter
Synlett
Table 2 (continued)
Supporting Information
Entry
(Het)Ar 5
Yield of 6 (%)a Yield of 7 (%)a RSM 5 (%)b
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1590832.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
o
nrtogI
f
rmoaitn
Br
6m
83 (A)
78 (B)
7m
0 (A)
0 (B)
5m
15 (A)
0 (B)
13
References and Notes
6n
7n
5n
S
14
90 (A)
58 (B)
0 (A)
0 (B)
6 (A)
0 (B)
(1) Tamaki, T.; Ohashi, M.; Ogoshi, S. Angew. Chem. Int. Ed. 2011, 50,
12067.
(2) (a) Liu, L.; Montgomery, J. J. Am. Chem. Soc. 2006, 128, 5348.
(b) Tamaki, T.; Nagata, M.; Ohashi, M.; Ogoshi, S. Chem. Eur. J.
2009, 15, 10083. (c) Ogoshi, S.; Nagata, M.; Kurosawa, H. J. Am.
Chem. Soc. 2006, 128, 5350.
(3) De Simone, F.; Waser, J. Chimia 2009, 63, 162.
(4) Blake, K. W.; Gillies, I.; Denney, R. C. J. Chem. Soc., Perkin Trans 1
1981, 700.
a Yields of isolated pure products.
b RSM = recovered starting material.
c Method A: Ar(Het)I (1.0 equiv), c-Pr3Bi (1.0 equiv), (SIPr)Pd(allyl)Cl (5
mol%), Na2CO3 (2.0 equiv), LiCl (2.0 equiv), DMF (0.1 M), 40 °C, 16 h.
d Method B: Ar(Het)I (1.0 equiv), c-Pr3Bi (1.5 equiv), (SIPr)Pd(allyl)Cl (10
mol%), Na2CO3 (2.0 equiv), LiCl (2.0 equiv), DMF (0.1 M), 80 °C, 16 h.
In summary, we developed a protocol for the carbonyla-
tive cross-coupling reaction of tricyclopropylbismuth with
aryl and heteroaryl iodides. The reaction operates under
simple and mild conditions, requires only 1 atm of carbon
monoxide, shows excellent functional-group compatibility,
and affords the desired aryl cyclopropylketones in good to
excellent yields. The use of lithium chloride as an additive
provided higher yields of the desired carbonylative prod-
ucts. Cyclopropylboronic acid, cyclopropylboronic acid pin-
acol ester, potassium cyclopropyltrifluoroborate, and cyclo-
propylboronic acid MIDA ester failed to afford the desired
carbonylative cross-coupling product. The conditions were
transposed to the carbonylative cross-coupling reaction of
iodoalkene 8, affording the corresponding cyclopropyl alke-
nylketone in good yield.
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Bi
O
2a
I
OBn
OBn
(SIPr)Pd(allyl)Cl
Na2CO3
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8
9
(1.0 equiv)
Method A: 61%
Method B: 55%
LiCl
CO (1 atm), DMF
Scheme 2 Palladium-catalyzed cross-coupling reaction between trans-
iodoalkene 8 and tricyclopropylbismuth (2a)
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Funding Information
This work was supported by a provincial Fonds de Recherche du Qué-
bec, Nature et Technologies (FRQNT) team grant and by the Centre in
Green Chemistry and Catalysis (CGCC).
)(
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Acknowledgment
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J.D. thanks UQAM for a FARE and a Fondation Hydro-Québec graduate
scholarship. The authors thank Emmanuelle Allouche and Pr. André B.
Charette from the chemistry departement of the Université de Mon-
tréal for kindly providing iodoalkene 8.
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© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F

F
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(48) Analytical Data for Compound 3
Pale yellow solid; Rf = 0.21 (10% EtOAc/hexane); mp 62.6 °C. 1H
NMR (300 MHz, CDCl3): δ = 8.12 (d, J = 8.7 Hz, 2 H), 8.07 (d, J =
8.7 Hz, 2 H), 3.94 (s, 3 H), 2.71–2.62 (m, 1 H), 1.29–1.24 (m, 2 H),
1.11–1.05 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 200.4,
166.4, 141.4, 133.6, 129.9, 128.0, 52.6, 17.8, 12.3 ppm. IR (neat):
2953, 2852, 1720, 1667, 1439, 1407, 1278, 1216, 1107, 1016,
993, 720 cm–1. ESI-HRMS: m/z calcd for C12H12O3: 204.0786;
found: 205.0855 [M + H]+.
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(51) Method A
A sealed tube equipped with a magnetic stirring bar was
charged with the aryl halide 1 or 5 (1.0 equiv), Na2CO3 (2.0
equiv), anhydrous LiCl (2.0 equiv) and (SIPr)Pd(allyl)Cl (0.05
equiv). Tricyclopropylbismuth (2a, 1.0 equiv) was dissolved in
anhydrous DMF (0.1 M) under argon and was added into the
sealed tube. CO was bubbled in the reaction mixture for 45 s,
then the tube was sealed and heated at 40 °C for 16 h. The reac-
tion mixture was cooled to r.t., transferred in a separatory
funnel containing 20 mL of an aq sat. NaHCO3 solution, and
extracted with EtOAc (3 × 20 mL). The combined organic layers
were washed with brine (30 mL), dried over anhydrous Na2SO4,
and concentrated under reduced pressure. The residue was
purified by flash column chromatography to afford the desired
aryl cyclopropyl ketone 3 or 6.
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(52) Method B
Same as method A except that 1.5 equiv of tricyclopropylbis-
muth (2a) instead of 1.0 equiv and 0.1 equiv of (SIPr)Pd(allyl)Cl
instead of 0.05 equiv were used, and that the reaction was
heated at 80 °C instead of 40 °C.
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© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F