Palladium-Catalyzed Room-Temperature Acylative Suzuki Coupling of High-Order Aryl Borons with Carboxylic Acids

Article abstract of DOI:10.1021/acs.joc.6b00421

This note describes a dimethyl dicarbonate-assisted, Pd(OAc)₂/PPh₃-catalyzed acylative Suzuki coupling of carboxylic acids with diarylborinic acids or tetraarylboronates for practical and efficient synthesis of sterically undemanding aryl ketones at room temperature. More than just cost-effective alternatives to aryl boronic acids, diarylborinic acids and tetraarylboronates displayed higher reactivity in the acylative Suzuki coupling. A variety of alkyl aryl ketones, including those bearing a hydroxy, bromo, or carbonyl group, could be readily obtained in modest to excellent yields.

Full text of DOI:10.1021/acs.joc.6b00421

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Note
Palladium-Catalyzed Room-Temperature Acylative Suzuki
Coupling of High-Order Aryl Borons with Carboxylic Acids
Shufen Si, Chen Wang, Nan Zhang, and Gang Zou
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00421 • Publication Date (Web): 21 Apr 2016
Downloaded from http://pubs.acs.org on April 23, 2016
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PalladiumꢀCatalyzed RoomꢀTemperature Acylative Suzuki Coupling of HighꢀOrder Aryl
Borons with Carboxylic Acids
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Shufen Si, Chen Wang, Nan Zhang and Gang Zou*
Department of Fine Chemicals, East China University of Science & Technology, 130 Meilong
Rd, Shanghai, China, Eꢀmail: zougang@ecust.edu.cn
Abstract: This note describes a dimethyl dicarbonate assisted, Pd(OAc)2/PPh3 catalyzed
acylative Suzuki coupling of carboxylic acids with diarylborinic acids or tetraarylboronates for
practical and efficient synthesis of sterically undemanding aryl ketones at room temperature.
More than just costꢀeffective alternatives to aryl boronic acids, diarylborinic acids and
tetraarylboronates displayed higher reactivity in the acylative Suzuki coupling. A variety of
alkyl aryl ketones including those bearing a hydroxy, bromo or carbonyl group could be
readily obtained in modest to excellent yields.
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Aryl ketones are not only key moieties of many biologically active molecules but also
versatile building blocks in organic synthesis. The traditional approaches to aryl ketones often
suffer from harsh reaction conditions, poor selectivities and/or functional group compatibility.1
Transition metalꢀcatalyzed reactions, such as carbonylative2 and acylative2b, 3 crossꢀcouplings
of halides and carbonyl compounds, especially carboxylic acid derivatives, have emerged with
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good
regioselectivity
and
functional
group
compatibility
and
become increasingly essential protocols for synthesis of aryl ketones. The acylative
crossꢀcoupling of carboxylic acid derivatives with aryl boronic acids (acylative Suzuki
coupling) is particularly attractive because both carboxylic acids4 and aryl boronic acids5 are
generally nonꢀtoxic, stable, easy to handle and readily available. Great progress has been
achieved on acylative Suzuki coupling with respect to acyl sources since its seminal report
using acyl chlorides by Bumagin et al.6 The milder acyl donors have been widely applied, e.g.
anhydrides7 including in-situ generated ones pioneered by Gooßen7b, 8 and Yamamoto et al.,7c,
active esters,10 especially the elegant Liebeskind’s enzymeꢀmimic thiol esters11 and, more
9
recently activated amides by Szostak,12 Garg13 and ourselves,14 independently. The
palladiumꢀcatalyzed procedures using in-situ generated anhydrides from carboxyl acids in the
presence of an activating reagent make the acylative Suzuki coupling more practical for
synthesis of aryl ketones. Besides the progress on acyl sources, a couple of transition metals
other than palladium, e.g. Ru,10a Rh,7a, 10c Cu,11c, 11e and Ni13 etc., have also been found to be
effective in catalyzing the acylative Suzuki coupling of anhydrides, esters and amides. In
contrast, aryl boronic acids have still overwhelmingly dominated the aryl source in acylative
Suzuki coupling of carboxylic acid derivatives. In fact, even the boronic anhydrides, triaryl
boroxines, were proposed to be rather unreactive in palladiumꢀcatalyzed acylative
crossꢀcouplings with carboxylic acid anhydrides.8 Therefore, a proper amount of water had to
be maintained in the system to prevent from dehydration of aryl boronic acids while excess
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water proved to be deleterious owing to competitive hydrolysis of acyl sources and/or
activating reagents for the in-situ procedures unless some unconventional systems were used.15
We have recently shown that highꢀorder aryl borons, such as diarylborinic acids and
tetraarylborates, could be used as costꢀeffective alternatives to aryl boronic acids in both
traditional and acylative Suzuki coupling of aryl (pseudo)halides16 and activated amides,14b
respectively. Given the lower reactivity of amides as acyl source, we rationalize that it should
be more facile to couple these highꢀorder aryl borons with the more reactive anhydrides
including the in-situ generated ones, through which carboxylic acids could be directly used as
acyl source. Herein, we report an efficient Pd(OAc)2/PPh3 catalyzed acylative Suzuki coupling
of diarylborinic acids or sodium tetraarylborates with carboxylic acids via in-situ generated
anhydrides by using dimethyl dicarbonate as activating reagent for practical and costꢀeffective
synthesis of aryl ketones at roomꢀtemperature.
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Initially, the reaction conditions developed by Gooßen et al8 for the coupling of aryl
boronic acids with in-situ generated anhydrides from carboxylic acids were adopted, i.e.
3mol% Pd(OAc)2 / 7mol%P(p-OMePh)3 as catalyst in the presence of 1.5equiv. pivalic
anhydride and 2.5equiv. water in THF under N2 at 60oC. The crossꢀcoupling of
hydrocinnamic acid (1a) with bis(p-tolyl)borinic acid (2a) was chosen as the model to
test the reactivity of diarylborinic acids considering that diphenylborinic acid (2b
)
readily dehydrates to form anhydride ((Ph2B)2O) (Table 1). The desired aryl ketone
3ꢀphenylꢀ1ꢀ(p-tolyl)propanꢀ1ꢀone (3aa) was obtained in a modest yield (60%).
Substitution of tri(p-anisoyl)phosphine with simpler and more economical
triphenylphosphine (TPP) gave almost the same yield (62%) although no reaction was
observed in the absence of a phosphine ligand (Table 1, entries 1, 2 and 4).
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Table 1 Parameter screening for crossꢀcoupling of hydrocinnamic acid with
bis(p-tolyl)borinic acida
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7
8
9
Entry
1
Cat. Pd/PR3 (mol%)
Pd(OAc)2(3) / P(p-MeOPh)3(7)
Pd(OAc)2(3) / PPh3(7)
Pd(OAc)2(PPh3)2(3)
Pd(OAc)2(3)
Activator
(t-BuCO)2O
(t-BuCO)2O
(t-BuCO)2O
(t-BuCO)2O
(t-BuCO)2O
(t-BuCO)2O
(t-BuCO)2O
(t-BuCO)2O
(t-BuCO)2O
(t-BuCO)2O
(t-BuCO)2O
(t-BuCO)2O
(t-BuCO)2O
(t-BuCO)2O
(t-BuCO)2O
(t-BuCO)2O
(t-BuCO)2O
(t-BuCO)2O
(t-BuCO)2O
(Boc)2O
H2O(eq.)
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
10
/
Sol.
T.(oC) Yield(%)b
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59
60
THF
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
rt
60
2
THF
62
3
THF
80
4
THF
trace
5
5
Pd(PPh3)2Cl2(3)
THF
6
Pd(PCy3)2Cl2(3)
THF
68
7
Pd(dppp)Cl2(3)
THF
58
8
Pd(OAc)2(PPh3)2(3)
Pd(OAc)2(PPh3)2(3)
Pd(OAc)2(PPh3)2(3)
Pd(OAc)2(PPh3)2(3)
Pd(OAc)2(PPh3)2(3)
Pd(OAc)2(PPh3)2(3)
Pd(OAc)2(PPh3)2(3)
Pd(OAc)2(PPh3)2(3)
Pd(OAc)2(PPh3)2(3)
Pd(OAc)2(PPh3)2(3)
Pd(OAc)2(PPh3)2(3)
Pd(OAc)2(PPh3)2(3)
Pd(OAc)2(PPh3)2(3)
Pd(OAc)2(PPh3)2(3)
Pd(OAc)2(PPh3)2(3)
Pd(OAc)2(PPh3)2(3)
Pd(OAc)2(PPh3)2(3)
Pd(OAc)2(PPh3)2(3)
Pd(OAc)2(3) / PPh3(6)
Pd(OAc)2(3) / PPh3(6)
Pd(OAc)2(3) / PPh3(9)
Pd(OAc)2(3) / PPh3(12)
Pd(OAc)2(3) / PPh3(3)
Pd(OAc)2(1) / PPh3(2)
Pd(OAc)2(3) / PPh3(6)
Pd(OAc)2(3) / PPh3(6)
Dioxane
Toluene
DME
DMF
Acetone
MeOH
CH3CN
EtOAc
EtOH
iꢀPrOH
n-Butanol
THF
65
9
28
10
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12
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16
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19
20
21
22
23
24
25
26
27
28
29
30
31
32
48
59
61
73
52
72
75
58
74
77c
THF
rt
35
RSC
THF
rt
trace
96
DMDC
THF
rt
DMDC
THF
rt
82
DMDC
THF
rt
99
DMDC
/
THF
rt
99d
99d
34d, e
72
DMDC
/
THF
rt
DMDC
/
THF
rt
DMDC
/
THF
rt
DMDC
/
THF
rt
24
DMDC
/
THF
rt
5
DMDC
/
THF
rt
82d
88d, f
22e, g
DMDC
/
THF
rt
33
DMDC
/
THF
rt
a
Reaction conditions: 1.0mmol 1a with 0.6mmol (1.2equiv. with respect to aryl group) 2a in the
b
c
presence of 1.5mmol (1.5equiv.) activator under nitrogen in anhydrous solvent. Isolated yields. 24
hours. d ACS grade THF used directly. e p-Tolylboronic acid used. f 1.0 equiv. DMDC used. g In air.
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This result is interesting because TPP was reported to be a much less efficient ligand
in the corresponding reaction of aryl boronic acids,8 implying the higher reactivity of
borinic acids than boronic acids in the acylative Suzuki coupling. Therefore, we
reꢀoptimized the reaction conditions for diarylborinic acids. Using the preformed
palladium acetate phosphine complex Pd(OAc)2(PPh3)2 as catalyst precursor, the yield
of 3aa increased to 80% under the otherwise identical conditions while the other tested
palladium complexes, PdCl2(PPh3)2, Pd(OAc)2(PCy3)2 and Pd(dppp)(OAc)2, performed
less efficiently (Table 1, entries 3, 5ꢀ7). THF appeared to be the choice of solvent after
surveying the common solvents, e.g. dioxane (65%), toluene (28%), glyme (DME,
48%), DMF (59%), acetone (61%), MeOH (73%), CH3CN (52%), ethyl acetate (72%),
EtOH (75%), i-PrOH (58%) and n-BuOH (74%) (Table 1, entries 8ꢀ18). No increase in
3aa yield was observed with longer reaction time (24 hours). Surprisingly, a
comparable yield (77%) could be obtained when the reaction was carried out at room
temperature for 24 hours (Table 1, entry 19). The advantages of roomꢀtemperature
organic synthesis17 motivated us to further screen the other parameters to improve the
reaction. While di-tert-butyl dicarbonate (Boc)2O and N,N’ꢀdisuccinimidyl carbonate
(DSC) provided much lower yields, an excellent yield (96%) of 3aa was obtained when
dimethyl dicarbonate (DMDC) was used as the activating reagent (Table 1, entries
20ꢀ22). The readily removed byꢀproducts and safety of DMDC18 further increased the
practicality of the method for synthesis of aryl ketones. The yields decreased
remarkably from 96 to 82% with increasing the amount of water from 2.5 to 10equiv.
with respect to carboxylic acid in the reaction system, indicating a competitive
sideꢀreaction of water. In fact, a quantitative yield (99%) was obtained when no water
was added (Table 1, entries 23 and 24). It is noteworthy to point out that commercial
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THF (ACS grade) could be used directly, showing no decease in 3aa yield from that
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distilled from sodium/benzophenone (Table 1, entry 25). A control experiment using
p-tolylboronic acid instead of bis(p-tolyl)borinic acid (2a) gave a low yield (34%) for
3aa under the anhydrous condition, conforming the higher reactivity of diarylborinic
acids than boronic acids in the acylative Suzuki coupling (Table 1, entry 27). To the
best of our knowledge, this represents the first example that diarylborinic acids showed
significantly higher reactivity than boronic acids in palladiumꢀcatalyzed
crossꢀcouplings. More practically, the combination of 3mol% Pd(OAc)2 with 6mol%
PPh3 worked as efficiently as Pd(OAc)2(PPh3)2 under the optimal conditions. Gooßen et
al had reported that high phosphine/palladium ratios, e.g. P/Pd > 3, suppressed the
activity of the Pd(OAc)2/PAr3 catalyst system in the corresponding reaction of
arylboronic acids.8 Similarly, significant decreases in yields of 3aa were observed with
increasing the ratios of phosphine/palladium to 3 (72%) and 4 (24%) (Table 1, entries
28 and 29), indicating the true catalytically active species should be a coordinatively
unsaturated palladium/phosphine complex. This competitive inhibition by extra
phosphine and the structureꢀdependent reactivity of boron partners, e.g. the higher
activity of diarylborinic acids than boronic acids which, in turn, are more reactive than
boroxines and boronates, imply that transmetalation between palladium and boron
species could be the rateꢀdetermining step in catalytic cycle. The yields of 3aa deceased
to 82% and 88% with lower (1mol%) catalyst or DMDC (1.0equiv.) loading,
respectively. When the reaction was conducted in air 3aa was obtained in low yield
(22%) with 4,4’ꢀdimethylbiphenyl, which formed in a trace amount under nitrogen
atmosphere, as the major byꢀproduct from the homoꢀcoupling of 2a (Table 1, entry 33).
The scope of the aryl ketone synthesis from carboxylic acids and diarylborinic acids
was briefly investigated with respect to steric and electronic factors as well as
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functional groups under the optimal conditions (Table 2).
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Table 2 Roomꢀtemperature palladiumꢀcatalyzed acylative Suzuki coupling of carboxyl
acids with diarylborinic acidsa
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a
Reaction conditions: 1.0mmol 1 with 0.6mmol (1.2equiv. with respect to aryl group) 2 under nitrogen in ACS
grade THF. b In form of anhydride >90%. c No reaction either for bis(o-anisoyl)borinic acid.
While the aryl boronic anhydrides, triaryl boroxines, were proposed to be much less
reactive than acids in palladiumꢀcatalyzed acylative Suzuki coupling, the dehydrated
diphenylborinic acid (2b) (>90% anhydride, (Ph2B)2O) gave 3ab in 96% yield.
Diarylborinic acids bearing a metaꢀsubstituent, e.g. MeO (2e) and Me (2f), reacted
similarly to their paraꢀsubstituted analogues (2a and 2c) to give 3ae (94%) and 3af
(94%), respectively, in excellent yields. Surprisingly, orthoꢀsubstituted aryl borinic
acids, e.g. bis(o-tolyl)borinic acid and bis(o-anisoyl)borinic acid, almost completely
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failed in the reaction with hydrocinnamic acid (1a) since we have observed that modest
hindrance from diarylborinic acids could be overcome in their acylative Suzuki
coupling with a variety of activated amides.14 This sharp difference in steric effect of
boron partner from reaction with acids to amides could be attributed to the shift of the
rateꢀdetermining step in catalytic cycle from transmetalation between boron and
palladium to oxidative addition of CꢀN bond of amide to palladium (vide supra). Alky
aryl ketones could be isolated in good to excellent yields from alkyl carboxylic acids
containing a remote common functional group, e.g. bromo (1b), carbonyl (1c), ester
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(
1d), hydroxyl (1e), or Bocꢀprotected amino (1f) although a free amino group destroyed
the activating reagent DMDC. It is noteworthy that the bromo group in
6ꢀbromohexanoic acid (1b) remained completely untouched by palladium catalyst,
thanks to the mild reaction conditions. As expected, steric factor from carboxyl acids
hampered seriously the acylative crossꢀcoupling since pivalic anhydride could be used
as the activating reagent without formation any detectable pivalophenone. In fact, no
reaction was observed for 1ꢀadamantane carboxylic acid while coupling of cyclohexane
carboxylic acid with bis(p-tolyl)borinic acid gave 3ga in a modest yield (64%). In
general, the aryl carboxylic acids showed slightly lower reactivities than the alkyl
analogues. After double reaction time (24h), the ketone yields from the reactions of
aromatic carboxylic acids even without steric hindrance were still lower than those of
alkyl analogues. An electronꢀdonating group, e.g. p-MeO (1p), or small
orthoꢀsubstituent, e.g. o-methyl, on the aromatic ring of benzoic acids further decreased
their reactivity, providing ketones 3pa and 3ka in just 45% and 58% yields,
respectively. Nicotinic acid (pyridineꢀ3ꢀcarboxylic acid, 1r) and isonicotinic acid
(pyridineꢀ4ꢀcarboxylic acid, 1s) reacted with 2a similarly to benzoic acids to give 3ra
and 3sa in 65 and 71% yields, respectively, while no desired product 3ta was obtained
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from picolinic acid (pyridineꢀ2ꢀcarboxylic acid) under the otherwise identical
conditions. Instead, a simple mixed anhydride, bis(p-tolyl)borinic picolinic anhydride,
was isolated in 95% yield, which is obviously stabilized by the chelating N/O
coordination of picolinic acid to boron and reluctant to transmetalate with palladium
species, the rateꢀdetermining step in the catalytic cycle.
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Utilization of tetraarylborates ([Ar4B]ꢀ) as aryl source in arylation processes is always
attractive because of their advantages over the other arylborons with respect to atom and
process economies, airꢀstability, handling and stoichiometry. However, the stronger reducing
abilities of higher order aryl borons19 make tetraarylborates reluctant in the transition metal
catalyzed arylation reactions unless highly reactive allylic derivatives used.20 Bumagin et al.
have reported that sodium tetraarylborates could couple with acyl chlorides in anhydrous
acetone.21 We have observed the coupling of sodium tetraarylborates with activated amides to
give aryl ketones in just slightly lower yields than diarylborinic and arylboronic acids.14
Therefore, we investigated the reactivity of sodium tetraarylborates in the DMDC assisted,
Pd(OAc)2/PPh3ꢀcatalyzed acylative Suzuki coupling with carboxylic acids under the optimal
conditions for diarylborinic acids (Table 3).
Representative sodium tetraarylborates, i.e. tetraphenylborate (4a), tetra(p-tolyl)borate
(4b), tetra(p-anisoyl)borate (4c), tetra(m-tolyl)borate (4d) and tetra(m-anisoyl)borate (4e)
reacted with hydrocinnamic acid (1a) and electronically varied benzoic acids, p-toluic acid
(1j), p-trifluoromethyl benzoic acid (1m) and p-anisic acid (1p), similarly to their
diarylborinic acid analogues to offer the corresponding aryl ketones 3ab-3if or 5ma/5pa albeit
in slightly lower yields (Table 3, entries 1ꢀ7, 10 and 11). An orthoꢀsubstituent on the ring of
benzoic acid, o-toluic acid (1k), again decreased the yield (54%) of diarylketone (5ka)
significantly compared with its para-substituted isomer (1j) in reaction with tetraphenylborate
(4a).
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Table 3 Palladiumꢀcatalyzed DMDCꢀassisted roomꢀtemperature acylative crossꢀcoupling of
carboxyl acids with sodium tetraarylborates a
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Entry
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R(1)
Ar(4)
Ph(4a)
T(h) Yield(%)b
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3ab, 90
2ꢀphenylethyl(1a)
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2ꢀphenylethyl(1a) p-MeC6H4(4b)
2ꢀphenylethyl(1a) p-MeOC6H4(4c)
2ꢀphenylethyl(1a) m-MeC6H4(4d)
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3aa, 91
3ac, 85
3af, 94
3ae, 92
3if, 72
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2ꢀphenylethyl(1a) m-MeOC6H4(4e) 12
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Ph(1i)
m-MeC6H4(4d)
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Ph(1i)
m-MeOC6H4(4e) 24
3ie, 69
3ia, 71
5ka, 54
5ma, 91
5pa, 42
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p-MeC6H4(1j)
o-MeC6H4(1k)
p-CF3C6H4(1m)
p-MeOC6H4(1p)
Ph(4a)
Ph(4a)
Ph(4a)
Ph(4a)
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a
Reaction conditions: 1.0mmol 1 with 0.3mmol (1.2equiv. with respect to aryl group) 4 under nitrogen in ACS
grade THF. b Isolated yields.
In summary, an efficient palladiumꢀcatalyzed acylative Suzuki coupling of diarylborinic
acids or tetraarylboronates with carboxylic acids via in-situ generated anhydrides by using
dimethyl dicarbonate as activating reagent is developed for practical synthesis of sterically
undemanding aryl ketones under mild conditions. The reaction showed a good tolerance to
common functional groups, in particular, the reactive alkyl bromide albeit being sensitive to
steric hindrance. Both diarylborinic acids and tetraarylboronates displayed significantly higher
reactivity than the corresponding aryl boronic acids. The other features of the approach for
aryl ketone synthesis include simple catalyst system, innocent activating reagent, easyꢀto
handle yet costꢀeffective aryl sources. These features make the in-situ procedure of carboxylic
acids complementary to our previously reported amide approach that worked well for
synthesis of sterically demanding aryl ketones under comparably rigorous conditions.
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Experimental Section
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General information: All reactions were carried out under nitrogen by using standard
Schlenk techniques unless otherwise stated. Commercially available chemicals were used as
received. Diarylborinic acids16a and sodium tetraarylborates14b were prepared according to
previously reported procedures. Column chromatograph was performed on 200ꢀ300 mesh
silica gal. 1H and 13C NMR spectra were recorded in CDCl3 at ambient temperature. Chemical
shifts in NMR are reported in ppm (δ), relative to the internal standard of tetramethylsilane
(TMS). The signals observed are described as s (singlet), d (doublet), t (triplet), q (quartet), dd
(double doublet), m (multiplets). The number of protons (n) for a given resonance is indicated
as nH. Coupling constants are reported as J in Hz. New compound 3fa was further
characterized by HRMS.
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General procedure for acylative Cross coupling of carboxylic acids with diarylborinic
acids or sodium tetraarylborates
To a 25mL Schlenk flask were added carboxylic acid (1.0mmol, 1.0equiv.), diarylborinic
acid (0.6mmol, 1.2equiv. with respect to aryl group) or sodium tetraarylborates (0.3mol,
1.2equiv. with respect to aryl group), Pd(OAc)2 (6.7mg, 0.03mmol, 3mol%), PPh3 (15.7mg,
0.06mmol, 6mol%), THF (4mL) and dimethyl dicarbonate (0.201g, 1.5mmol, 1.5equiv.). The
mixture was stirred at room temperature for 12 or 24 hours under nitrogen with the progress
monitored by TLC. When completed, the reaction was quenched by water (10mL) and
extracted with CH2Cl2 (3x10mL). The organic phase was dried over Na2SO4. Removal of
solvents by rotavapor followed by purification through flash column chromatography over
silica gel using ethyl acetate/petroleum ether (60ꢀ90oC) gradient gave products 3 or 5.
3ꢀPhenylꢀ1ꢀ(p-tolyl)propanꢀ1ꢀone (3aa):14a white solid, yield: 0.221g, 99% from reaction of
hydrocinnamic acid (1a) with di((pꢀtolyl)borinic acid (2a); 0.203g, 91% from reaction of 1a
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with sodium tetra(p-tolyl)borate (4b); m.p.: 67ꢀ69oC; HNMR (400 MHz, CDCl3) δ(ppm):
7.85 (d, J = 8.4 Hz, 2H), 7.31ꢀ7.17 (m, 7H), 3.26 (t, J = 7.6 Hz, 2H), 3.05 (t, J = 7.6 Hz, 2H),
2.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ(ppm): 198.9, 143.9, 141.4, 134.4, 129.3, 128.5,
128.4, 128.2, 126.1, 40.4, 30.2, 21.7.
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1,3ꢀDiphenylpropanꢀ1ꢀone (3ab):14b white solid, yield: 0.202g, 96% from reaction of
hydrocinnamic acid (1a) with diphenylborinic acid or anhydride (2a); 0.189g, 90% from
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reaction of 1a with sodium tetraphenylborate (4a); m.p.: 71ꢀ72oC; H NMR (400 MHz,
CDCl3) δ(ppm): 7.86 (d, J = 7.2Hz, 2H), 7.45 (t, J = 7.2Hz, 1H), 7.35 (t, J = 8.0 Hz, 2H),
7.22ꢀ7.09 (m, 5H), 3.20 (t, J = 8.0Hz, 2H), 2.97 (t, J = 8.0Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ(ppm): 199.3, 141.3, 136.9, 133.1, 128.7, 128.6, 128.5, 128.1, 126.2, 40.5, 30.2.
1ꢀ(4ꢀMethoxyphenyl)ꢀ3ꢀphenylpropanꢀ1ꢀone (3ac):3k white solid, yield: 0.223g, 93% from
reaction of hydrocinnamic acid (1a) with di(p-anisoyl)borinic acid (2c); 0.204g, 85% from
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reaction of 1a with sodium tetra( p-anisoyl)borate (4c); m.p.: 96ꢀ97oC; H NMR (400 MHz,
CDCl3) δ(ppm): 7.94 (d, J = 8.8 Hz, 2H), 7.32ꢀ7.20 (m, 5H), 6.91 (d, J = 8.8 Hz, 2H), 3.86 (s,
3H), 3.25 (t, J = 7.6 Hz, 2H), 3.05 (t, J = 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ(ppm):
197.8, 163.5, 141.5, 130.3, 130.0, 128.5, 128.4, 126.1, 113.8, 55.5, 40.1, 30.4.
1ꢀ(3ꢀMethoxyphenyl)ꢀ3ꢀphenylpropanꢀ1ꢀone (3ae):22 Light yellow oil, yield: 0.226g, 94%
from reaction of hydrocinnamic acid (1a) with di(m-anisoyl)borinic acid (2e); 0.221g, 92%
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from reaction of 1a with sodium tetra( m-anisoyl)borate (4e); H NMR (CDCl3, 400 MHz)
δ(ppm): 7.53ꢀ7.48 (m, 2H), 7.37ꢀ7.18 (m, 6H), 7.09 (d, J = 6.8 Hz, 1H), 3.83 (s, 3H), 3.28 (t, J
= 7.6 Hz, 2H), 3.06 (t, J = 8.0 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ(ppm): 199.1, 159.9,
141.3, 138.3, 129.6, 128.6, 128.5, 126.2, 120.7, 119.6, 112.3, 55.5, 40.6, 30.2.
3ꢀPhenylꢀ1ꢀ(mꢀtolyl)propanꢀ1ꢀone (3af): 22 Light yellow oil, yield: 0.221g, 94% from reaction
of hydrocinnamic acid (1a) with di((mꢀtolyl)borinic acid (2f); 0.200g, 89% from reaction of
hydrocinnamic acid (1a) with sodium tetra(mꢀtolyl)boronate (4d); 1H NMR (CDCl3, 400 MHz)
δ(ppm): 7.76ꢀ7.73 (m, 2H), 7.33ꢀ7.19 (m, 7H), 3.26 (t, J = 7.6 Hz, 2H), 3.04 (t, J = 7.6 Hz,
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2H), 2.37 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ(ppm): 199.5, 141.4, 138.4, 136.9, 133.9,
128.7, 128.6, 128.55, 128.5, 126.2, 125.3, 40.6, 30.2, 21.4.
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6ꢀBromoꢀ1ꢀ(p-tolyl)hexanꢀ1ꢀone (3ba):23 white solid, yield: 0.249g, 93%; m.p.: 66ꢀ68oC; H
NMR (400 MHz, CDCl3) δ(ppm): 7.86 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H), 3.43 (t, J
= 6.8Hz, 2H), 2.97(t, J = 6.8Hz, 2H), 2.41 (s, 3H), 1.95ꢀ1.88 (m, 2H), 1.80ꢀ1.72 (m, 2H),
1.57ꢀ1.50 (m, 2H ) ; 13C NMR (100 MHz, CDCl3) δ(ppm): 199.7, 143.8, 134.5, 129.3, 128.2,
38.2, 33.7, 32.7, 27.9, 23.4, 21.6.
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1ꢀ(p-Tolyl)pentaneꢀ1,4ꢀdione ( 3ca):24 white solid, yield: 0.173g, 91%; m.p.: 59ꢀ60oC; H
NMR (400 MHz, CDCl3) δ(ppm): 7.88 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 3.26 (t, J
= 6.4Hz, 2H), 2.88 (t, J = 6.4Hz, 2H), 2.41 (s, 3H), 2.26 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ(ppm): 207.4, 198.1, 143.9, 134.2, 129.3, 128.2, 37.1, 32.3, 30.1, 21.6.
Methyl 4ꢀoxoꢀ4ꢀ(p-tolyl)butanoate (3da):25 white solid, yield: 0.196g, 95%; m.p.: 51ꢀ53oC;
11H NMR (400 MHz, CDCl3) δ(ppm): 7.89 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 3.70
(s, 3H), 3.30 (t, J = 6.8Hz, 2H), 2.76 (t, J = 6.8Hz, 2H), 2.41 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ(ppm): 197.7, 173.4, 144.0, 134.1, 129.3, 128.1, 51.8, 33.3, 28.1, 21.6.
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6ꢀHydroxyꢀ1ꢀ(p-tolyl)hexanꢀ1ꢀone (3ea): white solid, yield: 0.144g, 70%; m.p.: 72ꢀ73oC; H
NMR (400 MHz, CDCl3) δ(ppm): 7.86 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 3.67 (t, J
= 6.4Hz, 2H), 2.96 (t, J = 7.2Hz, 2H), 2.41 (s, 3H), 1.80ꢀ1.73 (m, 3H), 1.66ꢀ1.59 (m, 2H),
1.49ꢀ1.42 (m, 2H ) ; 13C NMR (100 MHz, CDCl3) δ(ppm): 200.2, 143.7, 134.5, 129.3, 128.2,
62.6, 38.3, 32.5, 25.5, 24.0, 21.6; HRMS (EIꢀTOF) m/z [M+H]+ calcd for C13H19O2 207.1380,
found 207.1379.
6ꢀ((tert-Butoxycarbonyl)amino)ꢀ1ꢀ(pꢀtolyl)hexanꢀ1ꢀone (3fa): white solid, yield: 0.230, 95%;
m.p.: 67ꢀ69oC; 1H NMR (400 MHz, CDCl3) δ(ppm): 7.85 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.0
Hz, 2H), 4.58 (s, 1H), 3.15ꢀ3.10 (m, 2H), 2.95 (t, J = 7.6Hz, 2H), 2.41 (s, 3H), 1.78ꢀ1.71 (m,
2H), 1.55ꢀ1.49 (m, 2H), 1.44ꢀ1.37 (m, 11H ) ; 13C NMR (100 MHz, CDCl3) δ(ppm): 199.9,
156.0, 143.7, 134.5, 129.2, 128.2, 79.0, 40.4, 38.3, 30.0, 28.4, 26.5, 24.0, 21.6; HRMS
(EIꢀTOF) m/z [M+H]+ calcd for C18H27NO3306.2069, found 306.2063.
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Cyclohexyl(p-tolyl)methanone (3ga):14b white solid, yield: 0.129, 64%; m.p.: 63ꢀ65oC; H
NMR (400 MHz, CDCl3) δ(ppm): 7.85 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 3.27ꢀ3.20
(m, 1H), 2.40 (s, 3H), 1.89ꢀ1.81 (m, 4H), 1.74ꢀ1.71 (m, 1H), 1.54ꢀ1.25 (m, 5H) ; 13C NMR
(100 MHz, CDCl3) δ(ppm): 203.5, 143.4, 133.8, 129.3, 128.4, 45.5, 29.5, 26.0, 25.9, 21.6.
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Phenyl(pꢀtolyl)methanone (3ia):14b white solid, yield: 0.167g, 85% from reaction of benzoic
acid (1i) with di((pꢀtolyl)borinic acid (2a); 0.139g, 71% from reaction of pꢀtoluic acid (1j)
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with sodium tetraphenylborate (4a); m.p.: 58ꢀ60oC; HNMR (400 MHz, CDCl3) δ(ppm): 7.78
(d, J = 7.6Hz, 2H), 7.72 (d, J = 7.6 Hz, 2H), 7.57 (t, J = 7.6 Hz, 1H), 7.47 (t, J = 7.6 Hz, 2H),
7.28 (d, J = 8.0 Hz, 2H), 2.44 (s, 3H); 13C NMR (100 MHz, CDCl3) δ(ppm): 196.6, 143.3,
138.0, 134.9, 132.2, 130.3, 130.0, 129.0, 128.2, 21.7.
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Diꢀp-tolylmethanone (3ja):14b white solid, yield: 0.168g, 80%; m.p.: 96ꢀ97oC; HNMR (400
MHz, CDCl3) δ(ppm): 7.70 (d, J = 8.0Hz, 4H), 7.27 (d, J = 8.0 Hz, 4H), 2.43 (s, 6H); 13C
NMR (100 MHz, CDCl3) δ(ppm): 196.3, 143.0, 135.2, 130.2, 128.9, 21.7.
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oꢀTolyl(pꢀtolyl)methanone (3ka):14b light yellow oil, yield: 0.122g; 58%; H NMR (CDCl3,
400 MHz) δ(ppm): 7.72 (d, J = 8.4Hz, 2H), 7.40ꢀ7.36 (m, 1H), 7.30ꢀ7.22 (m, 5H), 2.42 (s,
3H), 2.31 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ(ppm): 198.4, 144.1, 139.0, 136.5, 135.1,
130.9, 130.3, 130.1, 129.2, 128.3, 125.2, 21.7, 19.9.
4ꢀFluorophenyl(p-tolyl)methanone (3la):14b white solid, yield: 0.193g, 90%; m.p.: 98ꢀ99oC;
1HNMR (400 MHz, CDCl3) δ(ppm): 7.82 (dd, J1 = 8.4 Hz, J2 = 5.6 Hz, 2H), 7.69 (d, J = 7.6
Hz, 2H), 7.29 (d, J = 7.6 Hz, 2H), 7.15 (t, J = 8.4 Hz, 2H), 2.44 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ(ppm): 195.1, 166.5 (d, JCF = 250Hz), 143.4, 134.8, 134.1(d, JCF = 12Hz), 132.5(d,
JCF = 9.1Hz), 130.2, 129.1, 115.5 (d, JCF = 21.8Hz), 21.7.
p-Tolyl(4ꢀ(trifluoromethyl)phenyl)methanone (3ma):14b white solid, yield: 0.243g, 92%; m.p.:
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136ꢀ138oC; H NMR (400 MHz, CDCl3) δ(ppm): 7.87 (d, J = 8.0Hz, 2H), 7.74(d, J = 8.8Hz,
2H), 7.72(d, J = 8.4Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 2.46 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ(ppm): 195.3, 144.1, 141.1, 134.1, 133.4 (q, JCF = 32.2Hz), 130.4, 130.0, 129.2,
125.3(q, JCF = 3.7Hz), 122.4, 21.7.
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1ꢀ(4ꢀ(4ꢀMethylbenzoyl)phenyl)ethanꢀ1ꢀone (3na):2c white solid, yield: 0.150g, 63%; m.p.:
108ꢀ110oC; 1H NMR (400 MHz,CDCl3) δ(ppm): 8.05 (d, J = 8.4 Hz, 2 H), 7.84 (d, J = 8.4 Hz,
2 H), 7.72 (d, J = 8.0 Hz, 2 H), 7.30 (d, J = 8.0 Hz, 2 H), 2.67 (s, 3 H), 2.45 (s, 3 H); 13C NMR
(100 MHz, CDCl3) δ(ppm): 197.6, 195.7, 144.0, 141.8, 139.4, 134.2, 130.3, 129.9, 129.2,
128.1, 26.9, 21.7.
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Methyl 4ꢀ(4ꢀmethylbenzoyl)benzoate (3oa):14b white solid, yield: 0.211g, 83%; m.p.:
125ꢀ127oC; 1H NMR (400 MHz,CDCl3) δ(ppm): 8.14 (d, J = 8.0 Hz, 2 H), 7.82 (d, J = 8.4 Hz,
2 H), 7.72 (d, J = 8.0 Hz, 2 H), 7.30 (d, J = 8.0 Hz, 2 H), 3.97 (s, 3 H), 2.45 (s, 3 H); 13C NMR
(100 MHz, CDCl3) δ(ppm): 195.7, 166.4, 143.9, 141.7, 134.3, 133.0, 130.3, 129.6, 129.5,
129.2, 52.4, 21.7.
4ꢀMethoxyphenyl(p-tolyl)methanone (3pa):14b white solid, yield: 0.102g, 45%; m.p.: 90ꢀ92oC;
1HNMR (400 MHz, CDCl3), δ(ppm): 7.84 (d, J = 8.4 Hz, 2H), 7.71 (d, J = 8.0 Hz, 2H), 7.30
(dd, J1 = 7.6Hz, J2 = 4.8 Hz, 4H), 3.94(s, 3H), 2.44 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ(ppm): 195.2, 153.9, 153.7, 143.4, 135.6, 134.7, 131.6, 130.2, 129.1, 120.8, 55.6, 21.7.
Naphthalenꢀ2ꢀyl(p-tolyl)methanone (3qa):11c white solid, yield: 0.185, 75%; m.p.: 89ꢀ91oC; 1H
NMR (400 MHz, CDCl3) δ(ppm): 8.25 (s, 1H), 7.93ꢀ7.90 (m, 4H), 7.78 (d, J = 8.0 Hz, 2H),
7.62ꢀ7.53 (m, 2H), 7.31 (d, J = 8.0 Hz, 2H), 2.46 (s, 3H); 13C NMR (100 MHz, CDCl3) δ(ppm):
196.5, 143.2, 135.2, 132.3, 131.6, 130.4, 129.4, 129.1, 128.23, 128.20, 127.8, 126.8, 125.9,
21.7.
pꢀTolylꢀ3ꢀpyridylmethanone (3ra):26 white solid, yield: 0.128g, 65%; m.p.: 74ꢀ76oC; 1H NMR
(400 MHz, CDCl3) δ(ppm) 8.98 (d, J = 1.6 Hz, 1H), 8.80 (dd, J1 = 4.8 Hz, J2 = 1.6 Hz, 1H),
8.11 (dd, J1 = 8.0 Hz, J2 = 2.0 Hz, 1H), 7.74 (d, J = 8.0 Hz, 2H), 7.45 (dd, J1 = 7.6 Hz, J2 = 4.8
Hz, 1H), 7.32 (d, J = 8.0 Hz, 2H), 2.46 (s, 3H); 13C NMR (100 MHz, CDCl3) δ(ppm) 194.6,
152.6, 150.8, 144.2, 137.2, 134.0, 133.5, 130.3, 129.3, 123.4, 21.7.
p-Tolylꢀ4ꢀpyridylmethanone (3sa):27 white solid, yield: 0.140g, 71%; m.p.: 94ꢀ95 oC; 1H NMR
(400 MHz, CDCl3) δ(ppm): 8.80 (dd, J1 = 4.4 Hz, J2 = 1.6 Hz, 2H), 7.73 (d, J = 8.0 Hz, 2H),
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(3ꢀMethoxyphenyl)(phenyl)methanone (3ie):28 Light yellow oil, yield: 0.157g, 74% from
reaction of benzoic acid (1i) with di(m-anisoyl)borinic acid (2e); 0.146g, 69% from reaction of
1i with sodium tetra( m-anisoyl)borate (4e); 1H NMR (CDCl3, 400 MHz) δ(ppm): 7.80 (d, J =
7.4 Hz, 2H), 7.59ꢀ7.55 (m, 1H), 7.48ꢀ7.44 (m, 2H), 7.38ꢀ7.32 (m, 3H), 7.13ꢀ7.11 (m, 1H), 3.83
(s, 3H); 13C NMR (CDCl3, 100 MHz) δ(ppm): 196.5, 159.6, 138.9, 137.6, 132.5, 130.1, 129.3,
128.3, 122.9, 118.8, 114.4, 55.5.
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(3ꢀMethylphenyl)(phenyl)methanone (3if):28 Light yellow oil, yield: 0.149, 76% from reaction
of benzoic acid (1i) with di((mꢀtolyl)borinic acid (2f); 0.141g, 72% from reaction of
1
benzoic acid (1i) with sodium tetra(mꢀtolyl)boronate (4d); H NMR (CDCl3, 400 MHz)
δ(ppm): 7.80 (d, J = 7.6 Hz, 2H), 7.63ꢀ7.56 (m, 3H), 7.49ꢀ7.45 (m, 2H), 7.40ꢀ7.33 (m, 2H),
2.41 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ(ppm): 197.0, 138.2, 137.8, 137.6, 133.2, 132.4,
130.5, 130.1, 128.3, 128.1, 127.4, 21.4.
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Phenyl(oꢀtolyl)methanone 5ka14a: light yellow oil, yield: 0.106g, 54%; H NMR (CDCl3, 400
MHz) δ(ppm): 7.72 (d, J = 8.8 Hz, 2H), 7.50 (t, J = 7.6 Hz, 1H), 7.37 (t, J = 7.6 Hz, 2H),
7.33ꢀ7.29 (m, 1H), 7.22 (t, J = 8.4 Hz, 2H), 7.16 (t, J = 7.6 Hz, 1H), 2.25 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ(ppm): 198.7, 138.6, 137.7, 136.8, 133.2, 131.0, 130.3, 130.2, 128.54,
128.5, 125.2, 20.0.
Phenyl(4ꢀ(trifluoromethyl)phenyl)methanone 5ma14a: white solid, yield: 0.227g, 91%; m.p.:
115ꢀ117 oC; 1H NMR (CDCl3, 400 MHz) δ(ppm): 7.89 (d, J = 8.0 Hz, 2H), 7.81 (d, J = 6.8 Hz,
2H), 7.76 (d, J = 8.0 Hz, 2H), 7.63 (t, J = 7.2 Hz, 1H), 7.51 (t, J = 7.6 Hz, 2H); 13C NMR
(CDCl3, 100 MHz) δ(ppm): 195.5, 140.7, 136.7, 133.7 (q, JCF = 32.5 Hz), 133.1, 130.2, 130.1,
128.5, 125.3 (q, JCF = 3.7 Hz), 124.0 (q, JCF = 271.1 Hz).
(4ꢀMethoxyphenyl)(phenyl)methanone 5pa14a: white solid, yield: 0.890g, 42%; m.p.: 58ꢀ60
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oC; H NMR (CDCl3, 400 MHz) δ(ppm): 7.82 (d, J = 8.8 Hz, 2H), 7.75 (d, J = 6.8 Hz, 2H),
7.56 (t, J = 7.2 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 6.96 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H); 13C
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NMR (CDCl3, 100 MHz) δ(ppm): 195.6, 163.2, 138.3, 132.6, 131.9, 130.1, 129.7, 128.2,
113.6, 55.5.
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Acknowledgements
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We are grateful for financial support provided by the National Natural Science
Foundation of China (No. 21472041).
Supporting Information
HRMS of 3ea and 3fa and 1H and 13C NMR spectra of all products are available free of
charge via the Internet at http://pubs.acs.org.
References
(1) (a) Larock, R. C. Comprehensive Organic Transformations: A Guide to Functional Group
Preparations, VCH, New York, 1989, pp.685ꢀ702. (b) Dieter, R. K. Tetrahedron 1999, 55,
4177ꢀ4236. (c) Ross, J.; Xiao, J. Green Chem. 2002, 4, 129ꢀ133. (d) Sartori, G.; Maggi, R.
Chem. Rev. 2011, 111, 1077ꢀ1104.
(2) (a) Wu, X.ꢀF.; Neumann, H.; Beller, M. Chem. Soc. Rev. 2011, 40, 4986ꢀ5009. (b)
Blangetti, M.; Rosso, H.; Prandi, C.; Deagostino, A.; Venturello, P. Molecules 2013, 18,
1188ꢀ1213. (c) Bjergund, K. M.; Skrydstrup, T.; Molander, G. A. Org. Lett. 2014, 16,
1888ꢀ1891.
(3) For recent examples: (a) Lee, D.; Ryu, T.; Park, Y.; Lee, P. H. Org. Lett. 2014, 16,
1144ꢀ1147. (b) Wang, X.; F.ꢀD.; Liu, Tu, H.ꢀY.; Zhang A.ꢀD. J. Org. Chem. 2014, 79,
6554ꢀ6562. For early examples: (c) Schmink, J. R.; Krska, S. W. J. Am. Chem. Soc. 2011, 133,
19574ꢀ19577 and references cited therein.
(4) Gooßen, L. J.; Rodriguez, N.; Gooßen, K. Angew. Chem. Int. Ed. 2008, 47, 3100ꢀ3120.
(5) Hall, D. G., Eds.; Boronic Acids: Preparation, Applications in Organic Synthesis and
Medicine, 2 ed, WilleyꢀVCH: Weinheim, 2011.
(6) Bykov, V. V.; Korolev, D. N.; Bumagin, N. A. Russ. Chem. Bull. 1997, 46, 1631ꢀ1632.
17
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Page 18 of 19
1
2
3
4
(7) (a) Frost, C. G.; Wadsworth, K. J. Chem. Commun. 2001, 2316ꢀ2317. (b) Gooßen, L. J.;
Ghosh, K. Angew. Chem., Int. Ed. 2001, 40, 3458ꢀ3460. (c) Kakino, R.; Shimizu, I.;
Yamamoto, A. Bull. Chem. Soc. Jpn. 2001, 74, 371ꢀ376. (d) Shen, X.ꢀB.; Gao, T.ꢀT.; Lu, J.ꢀM.;
Shao, L.ꢀX. Appl. Organomet. Chem. 2011, 25, 497ꢀ501. (e) Yu, A.; Shen, L.; Cui, X.; Peng,
D.; Wu, Y. Tetrahedron 2012, 68, 2283ꢀ2288.
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(8) (a) Gooßen, L. J.; Ghosh, K. Eur. J. Org. Chem. 2002, 3254ꢀ3267. (b) Goossen, L. J.;
Ghosh, K. Chem. Commun. 2001, 2084ꢀ2085. (c) Goossen, L. J.; Winkel, L.; Doehring, A.;
Ghosh, K.; Paetzold, J. Synlett 2002, 1237ꢀ1240.
(9) (a) Kakino, R.; Narahashi, H.; Shimizu, I.; Yamamoto, A. Chem. Lett. 2001, 1242ꢀ1243. (b)
Kakino, R.; Yasumi, S.; Shimizu, I.; Yamamoto, A. Bull. Chem. Soc. Jpn. 2002, 75, 137ꢀ148.
(c) Kakino, R.; Narahashi, H.; Shimizu, I.; Yamamoto, A. Bull. Chem. Soc. Jpn. 2002, 75,
1333ꢀ1345.
(10) (a) Tatamidani, H.; Yokota, K.; Kakiuchi, F. N. Chatani, J. Org. Chem. 2004, 69,
5615ꢀ5621; (b) Tatamidani, H.; Kakiuchi, F.; Chatani, N. Org. Lett. 2004, 6, 3597ꢀ3599. (c)
Wang, J.; Zuo, S.; Chen, W.; Zhang, X.; Tan, K.; Tian, Y.; Wang, J. J. Org. Chem. 2013,
78, 8217ꢀ8231.
(11) (a) Liebeskind, L. S.; Srogl, J. J. Am. Chem. Soc. 2000, 122, 11260ꢀ11261. (b) Savarin, C.;
Srogl, J.; Liebeskind, L. Org. Lett. 2000, 2, 3229ꢀ3231. (c) Villalobos, J. M.; Srogl, J.;
Liebeskind, L. S. J. Am. Chem. Soc. 2007, 129, 15734ꢀ15735. (d) Zhang, Z.; Lindale, M. G.;
Liebeskind, L. S. J. Am. Chem. Soc. 2011, 133, 6403ꢀ6410. (e) VarelaꢀÁlvarez, A.;
Liebeskind, L. S.; Musaev, D. G. Organometallics 2012, 31, 7958ꢀ7968.
(12) (a) Meng, G.; Szostak, M. Org. Lett. 2015, 17, 4364ꢀ4367. (b) Meng, G.; Szostak, M. Org.
Biomol. Chem. 2016, 14, DOI: 10.1039/c6ob00084c.
(13) Weires, N. A.; Baker, E. L.; Garg, N. K. Nat. Chem. 2016, 8, 75ꢀ79.
(14) (a) Li, X.; Zou, G. Chem. Commun. 2015, 51, 5089. (b) Li, X.; Zou, G. J. Organomet.
Chem. 2015, 794, 136ꢀ145.
(15) Xin, B.; Zhang, Y.; Cheng, K. J. Org. Chem. 2006, 71, 5725ꢀ5731. (b) Mondala, M.; Bora,
U. Appl. Organomet. Chem. 2014, 28, 354ꢀ358.
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2
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5
6
7
8
9
(16) (a) Chen, X.; Ke, H.; Chen, Y.; Guan, C.; Zou, G. J. Org. Chem. 2012, 77, 7572ꢀ7578. b)
Chen, X.; Ke, H.; Zou, G. ACS Catal. 2014, 4, 379ꢀ385. c) Ke, H.; Chen, X.; Zou, G. J. Org.
Chem. 2014, 79, 7132ꢀ7140. (d) Ke, H.; Chen, X.; Feng, Y.; Zou, G. Sci. Chin. Chem. 2014,
57, 1126ꢀ1131.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
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44
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46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(17) Brahmachari, G. Room Temperature Organic Synthesis, Elsevier, 2015.
(18) Dimethyl dicarbonate (DMDC) is a beverage preservative, see: US Food and Drug
Administration: Food Additives Status List.
(19) (a) Turner, W. R.; Elving, P. J. Anal. Chem. 1965, 37, 207ꢀ211. (b) Geske, D. H. J. Phys.
Chem. 1959, 63, 1062ꢀ1070.
(20) (a) Partyka, D. V. Chem. Rev. 2011, 111, 1529ꢀ1595. For recent examples on
crossꢀcoupling of allylic electrophiles, see: (b) Sarkar, S. M.; Uozumi, Y.; Yamada, Y. M. A.
Angew. Chem. Int. Ed. 2011, 50, 9437ꢀ9441. (c) Yamada, Y. M. A.; Sarkar, S. M.; Uozumi, Y.
J. Am. Chem. Soc. 2012, 134, 3190ꢀ3198. (d) Hamasaka, G.; Sakurai, F.; Uozumi, Y. Chem.
Commun. 2015, 51, 3886ꢀ3888.
(21) Bmnagin, N. A.; Korolev, D. N. Tetrahedron Lett. 1999, 40, 3057ꢀ3060.
(22) Colbon, P.; Ruan, J.; Purdie, M.; Xiao JꢀL. Org. Lett. 2010, 12, 3670ꢀ3673.
(23) Marcel, H.; Sigrid, Z.; Beatrice, A.; Bernd, K.; Artur, K.; Ralf, B., Lars, K.; Christian, D.
K.; Rolf, W. H. Molecules 2008, 13, 1081ꢀ1110.
(24) Biava, M.; Porretta, G. C.; Poce, G.; Supino,S.; Forli, S.; Rovini, M.; Cappelli, A.;
Manetti, F.; Botta, M.; Sautebin, L.; Rossi, A.; Pergola, C.; Ghelardini, C.; Vivoli, E.;
Makovec, F.; Anzellotti, P.; Patrignani, P.; Anzini, M. J. Med. Chem. 2007, 50, 5403ꢀ5411.
(25) Jo, E.ꢀA.; Jun, C.ꢀH. Eur. J. Org. Chem. 2006, 2504ꢀ2507.
(26) Maerten, E.; Sauthier, M.; Mortreux, A.; Castanet, Y. Tetrahedron 2007, 63, 682ꢀ689.
(27) Leventis, N.; Rawaswdeh, A. M.; Zhang, G.; Elder, I. A.; Leventis, C. S. J. Org. Chem.
2002, 67, 7501ꢀ7510.
(28) Rao, M. L. N.; Venkatesh, V.; Banerjee, D. Tetrahedron 2007, 63, 12917ꢀ12926.
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