An aerobic ligandless palladium acetate catalysed Suzuki-Miyaura cross-coupling reaction in an aqueous solvent

Article abstract of DOI:10.3184/030823408X349952

The Suzuki-Miyaura reaction of aryl iodides and aryl bromides was catalysed by Pd(OAc)₂ (1 mol%) using K₃PO₄-3H ₂O (2 equiv) as base in dimethyl acetamide DMA-H₂O (1:1) at room temperature. Changes in the loading of Pd(OAc)₂ (from 1 mol% to 2 mol%), temperature (from room temperature to 80°C) and the ratio of DMA to water (from 1:1 to 5:1) resulted in the successful coupling of activated aryl chlorides with phenylboronic acid.

Full text of DOI:10.3184/030823408X349952

JOURNALꢀOFꢀCHEMICALꢀRESEARCHꢀ2008ꢀ
SEPTEMBER,ꢀ525–527ꢀ
RESEARCHꢀPAPERꢀ 525
An aerobic ligandless palladium acetate catalysed Suzuki–Miyaura
cross-coupling reaction in an aqueous solvent
a,b
a
a
Chen Li , Xiao-Qiang Li and Chi Zhang *
a
The State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, P. R. China
bThe Key Laboratory of Catalytic Technology, Tianjin Chemical Research & Design Institute, CNOOC, P.R. China
The Suzuki–Miyaura reaction of aryl iodides and aryl bromides was catalysed by Pd(OAc) (1 mol%) using K PO ·3H O
2
3
4
2
(
(
5
2 equiv) as base in dimethyl acetamide DMA-H O (1ꢀ: ꢀ1 ) at room temperature. Changes in the loading of Pd(OAc)
from 1 mol% to 2 mol%), temperature (from room temperature to 80°C) and the ratio of DMA to water (from 1ꢀ: ꢀ1 to
ꢀ: ꢀ1 ) resulted in the successful coupling of activated aryl chlorides with phenylboronic acid.
2
2
Keywordsꢀ:ꢀꢀSuzuki–Miyauraꢀreaction,ꢀligandless,ꢀpalladiumꢀacetate,ꢀaqueousꢀsolvent
Theꢀ palladium–catalysedꢀ Suzuki–Miyauraꢀ cross-couplingꢀ
ofꢀarylꢀhalidesꢀwithꢀarylboronicꢀacidsꢀhasꢀbecomeꢀoneꢀofꢀtheꢀ
mostꢀimportantꢀmethodsꢀforꢀtheꢀsynthesisꢀofꢀunsymmetricalꢀ
desiredꢀ cross-couplingꢀ productsꢀ inꢀ excellentꢀ yieldsꢀ (entriesꢀ
3–11ꢀandꢀentriesꢀ14–17).ꢀAsꢀforꢀtheꢀtwoꢀbromobenzoicꢀacids,ꢀ
4-bromobenzoic ꢀa cid ꢀ( entry ꢀ1 2) ꢀa nd ꢀ3 -bromobenzoic ꢀa cid ꢀ( entryꢀ
13),ꢀtheꢀcouplingꢀreactionꢀneededꢀ9hꢀandꢀ3hꢀrespectivelyꢀforꢀ
theꢀfullꢀconversionꢀofꢀsubstrates.ꢀItꢀwasꢀworthꢀnotingꢀthatꢀarylꢀ
bromidesꢀ orꢀ arylboronicꢀ acidsꢀ containingꢀ ortho-substituentsꢀ
1
,2
3,4
biaryls. ꢀGenerally,ꢀphosphineꢀligands ꢀhaveꢀbeenꢀusedꢀtoꢀ
guaranteeꢀtheꢀexcellentꢀyieldsꢀofꢀtheꢀcross-couplingꢀreaction.ꢀ
However,ꢀ manyꢀ phosphineꢀ ligandsꢀ areꢀ sensitiveꢀ toꢀ air;ꢀ andꢀ
thereꢀ areꢀ otherꢀ problemsꢀ associatedꢀ withꢀ theꢀ ligandsꢀ usage,ꢀ
5
suchꢀasꢀphosphoniumꢀsaltꢀformation ꢀandꢀaryl–arylꢀexchangeꢀ
Table 1 Effects of solvents and bases on Pd(OAc)2-catalysed
coupling reaction of 4-bromotoluene with phenylboronic acid
at room temperaturea
6
reaction. ꢀ Consequentlyꢀ theꢀ developmentꢀ ofꢀ ligandlessꢀ
palladium-catalysedꢀ Suzuki–Miyauraꢀ reactionsꢀ hasꢀ receivedꢀ
attentionꢀinꢀtheꢀpastꢀdecade.7-15
2
Pd(OAc) (1 mol %)
Br
+
PhB(OH)
2
base (2 equiv)
Ourꢀ researchꢀ interestsꢀ inꢀ Suzuki–Miyauraꢀ cross-couplingꢀ
lie in the development of highly efficient water-soluble
ligandsꢀforꢀcross-couplingꢀreactions.ꢀInꢀtheꢀcourseꢀofꢀstudies,ꢀ
1.5 equiv
solvent (6 mL), rt
Yield/%b
Entry
Base
Solvent
weꢀfoundꢀthatꢀ1ꢀmol%ꢀofꢀPd(OAc) ꢀwasꢀableꢀtoꢀcatalyseꢀtheꢀ
2
1c
2
Na2CO3
CH3CN/H2O (1ꢀ:ꢀ1)
CH CN/H O (1ꢀ:ꢀ1)
98
30
52
76
92
92
96
97
98
Suzuki–Miyauraꢀ cross-couplingꢀ ofꢀ 4-bromotolueneꢀ withꢀ
phenylboronicꢀ acidꢀ inꢀ aqueousꢀ acetonitrileꢀ atꢀ 80ꢀ°Cꢀ withoutꢀ
addedꢀligands.ꢀThisꢀaffordedꢀ4-methylbiphenylꢀinꢀaꢀyieldꢀofꢀ
2
Na CO3
3
2
3
Na CO3
THF/H O (2ꢀ:ꢀ1)
2
2
4
Na CO3
DME/H O (2ꢀ:ꢀ1)
2
2
9
8%ꢀ withꢀ sodiumꢀ carbonateꢀ asꢀ theꢀ baseꢀ (Tableꢀ 1,ꢀ entryꢀ 1).ꢀ
5
Na CO3
DMF/H O (2ꢀ:ꢀ1)
2
2
However,ꢀ theꢀ yieldꢀ decreasedꢀ dramaticallyꢀ toꢀ onlyꢀ 30%ꢀ
whenꢀreactionꢀwasꢀcarriedꢀoutꢀatꢀroomꢀtemperatureꢀ(entryꢀ2).ꢀ
InꢀaqueousꢀetherealꢀsolventsꢀsuchꢀasꢀTHFꢀ(entryꢀ3)ꢀandꢀDMEꢀ
6d
Na CO3
DMF/H O (2ꢀ:ꢀ1)
2
2
7
8
9
Na2CO3
DMA/H2O (2ꢀ:ꢀ1)
K PO ·3H O
DMF/H O (2ꢀ:ꢀ1)
3
4
2
2
d
K PO ·3H O
DMA/H O (1ꢀ:ꢀ1)
3
4
2
2
(entryꢀ4),ꢀtheꢀreactionꢀgaveꢀ4-methylbiphenylꢀinꢀtheꢀyieldꢀofꢀ
aUnless otherwise indicated, all reactions were performed
5
2%ꢀandꢀ76%ꢀrespectively.ꢀEncouragingly,ꢀwhenꢀpolarꢀaproticꢀ
with 1.0 mmol of 4-bromotoluene at room temperature for
solventsꢀ suchꢀ asꢀ DMFꢀ andꢀ DMAꢀ (N,N-dimethylacetamide)ꢀ
were used, excellent yields (≥ 92%) of 4-methylbiphenyl
wereꢀ attainedꢀ atꢀ roomꢀ temperatureꢀ (entriesꢀ 5–7).ꢀ Whenꢀ
K PO ·3H OꢀwasꢀusedꢀinsteadꢀofꢀNa CO ꢀinꢀaqueousꢀDMFꢀ
b
c
1
6–17 h under N2. Isolated yield. Reaction was run at 80ꢀ°C.
d
Coupling reaction was carried out in air.
3
4
2
2
3
Table 2 Suzuki–Miyaura coupling of aryl iodides and bromides
andꢀDMAꢀ(entriesꢀ8ꢀandꢀ9),ꢀalmostꢀquantitativeꢀyieldsꢀofꢀ4-
methylbiphenylꢀwereꢀobtained.ꢀComparedꢀwithꢀDMF,ꢀDMAꢀ
wasꢀtheꢀchoiceꢀofꢀorganicꢀsolventꢀsinceꢀitꢀresultedꢀinꢀanꢀevenꢀ
higherꢀyieldꢀofꢀ4-methylbiphenylꢀwithꢀaꢀsmallerꢀamountꢀusedꢀ
inꢀtheꢀreactionꢀ(entriesꢀ8ꢀandꢀ9).ꢀItꢀwasꢀworthꢀnotingꢀthatꢀtheꢀ
yieldꢀ ofꢀ cross-couplingꢀ productꢀ wasꢀ notꢀ affectedꢀ whenꢀ theꢀ
reactionꢀwasꢀcarriedꢀoutꢀinꢀairꢀ(entriesꢀ5,ꢀ6,ꢀ8ꢀandꢀ9).ꢀFurtherꢀ
decreasingꢀ theꢀ totalꢀ volumeꢀ ofꢀ aqueousꢀ DMAꢀ fromꢀ 6ꢀ mlꢀ
a
with arylboronic acids in DMA–H O at room temperature
2
Pd(OAc)
2
(1 mol %)
X
+
B(OH)2
R
1
R2
K
3
PO
4
·3H
2
O (2 equiv) R1
R
2
DMA / H
rt , air
2
O= 1:1 (4 mL)
X=Br, I
1.5 equiv
Entry
X
R1
R2
Time/h Yield/%b
1c
2
3
4
5
6
7
8
9
I
4-OMe
2-NO2
4-Me
H
H
H
H
H
H
H
H
H
H
6
94
98
98
98
99
98
98
99
98
95
99
96
90
99
99
89
90
I
6
(entryꢀ9)ꢀtoꢀ4ꢀmlꢀproducedꢀanꢀunchangedꢀyieldꢀofꢀ4-methyl-
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
0.5
0.2
0.4
0.5
0.8
0.8
0.5
0.8
0.5
9
biphenyl.ꢀ Thus,ꢀ aꢀ convenientꢀ ligandlessꢀ procedureꢀ forꢀ theꢀ
Suzuki–Miyauraꢀ cross-couplingꢀ reactionꢀ wasꢀ developedꢀ
whichꢀwasꢀrunꢀinꢀairꢀatꢀroomꢀtemperatureꢀ(Schemeꢀ1).
Underꢀtheseꢀoptimisedꢀreactionꢀconditions,ꢀarylꢀiodidesꢀandꢀ
arylꢀbromidesꢀwereꢀcoupledꢀwithꢀarylboronicꢀacidsꢀprovidingꢀ
theꢀ correspondingꢀ cross-couplingꢀ productsꢀ inꢀ excellentꢀ
yields.ꢀTwoꢀarylꢀiodides,ꢀ4-iodoanisoleꢀ(Tableꢀ2,ꢀentryꢀ1)ꢀandꢀ
4-CN
4-OMe
4-CHO
4-OH
4-NHAc
4-NO2
4-COOEt
4-Me
4-COOH
3-COOH
4-Me
1
1
0
1
4-OMe
d
d
2
-nitroiodobenzeneꢀ(entryꢀ2)ꢀwereꢀtested,ꢀandꢀexcellentꢀyieldsꢀ
12
13
H
H
ofꢀcross-couplingꢀproductsꢀwereꢀobtainedꢀafterꢀ6ꢀhours.ꢀExceptꢀ
forꢀtwoꢀbromobenzoicꢀacids,ꢀtheꢀcouplingꢀreactionsꢀofꢀallꢀotherꢀ
arylꢀ bromides,ꢀ para-substitutedꢀ orꢀ evenꢀ ortho-substitutedꢀ
arylꢀ bromidesꢀ (eitherꢀ electronꢀ withdrawingꢀ orꢀ electronꢀ
donatingꢀgroups)ꢀwereꢀcompletedꢀwithinꢀ1ꢀhour,ꢀaffordingꢀtheꢀ
3
1
1
1
1
4
5
6
7
2-OMe
H
2-OMe
H
0.5
0.5
0.5
0.5
2-Me-4-OMe
2-Me
2-Me
a
Unless otherwise indicated, all reactions were performed with 1.0
b
c
mmol of aryl iodides or aryl bromides. Isolated yield. Conversion
was 96%. Three equivalents of K PO ·3H O were used.
*
ꢀCorrespondent.ꢀE-mail:ꢀzhangchi@nankai.edu.cn
d
3
4
2

5
26ꢀ JOURNALꢀOFꢀCHEMICALꢀRESEARCHꢀ2008
Pd(OAc) (1 mol %)
2
Br
+
PhB(OH)2
K PO ·3H O (2 equiv)
1.5 equiv
3
4
2
DMA / H O (1:1) (4 mL)
2
98%
rt , air
Scheme 1ꢀ OptimalꢀreactionꢀconditionsꢀforꢀPd(OAc) -catalysedꢀSuzuki–Miyauraꢀcouplingꢀreactionꢀofꢀ4-bromotoluene.
2
onꢀtheꢀaromaticꢀringsꢀalsoꢀworkedꢀwellꢀinꢀtheꢀcross-couplingꢀ
reactionꢀ (entriesꢀ 14–17).ꢀ Typically,ꢀ theꢀ successfulꢀ couplingꢀ
ofꢀ 2-bromotolueneꢀ withꢀ 2-methoxyphenylboronicꢀ acidꢀ gaveꢀ
General procedure for Suzuki–Miyaura reaction
Aꢀmixtureꢀofꢀ1ꢀmmolꢀofꢀarylꢀiodidesꢀorꢀarylꢀbromides,ꢀarylboronicꢀ
acidꢀ (1.5ꢀ mmol),ꢀ K PO ·3H Oꢀ (533ꢀ mg,ꢀ 2ꢀ mmol)ꢀ andꢀ Pd(OAc) ꢀ
3
4
2
2
(
2.2ꢀmg,ꢀ0.01ꢀmmol)ꢀinꢀ4ꢀmlꢀofꢀDMA-H Oꢀ(1ꢀ:ꢀ1)ꢀwasꢀstirredꢀatꢀroomꢀ
2
2
'-methoxy-2-methylbiphenylꢀinꢀaꢀyieldꢀofꢀ89%ꢀafterꢀ30ꢀminꢀ
temperature.ꢀUponꢀcompleteꢀconsumptionꢀofꢀsubstratesꢀasꢀdeterminedꢀ
byꢀTLC,ꢀ NaOHꢀ (1ꢀ M)ꢀ solutionꢀ 10ꢀ mlꢀ wasꢀ addedꢀ andꢀ theꢀ mixtureꢀ
wasꢀthenꢀextractedꢀwithꢀEtOAcꢀ(4ꢀ×ꢀ20ꢀml).ꢀTheꢀcombinedꢀorganicꢀ
layerꢀwasꢀwashedꢀwithꢀwaterꢀ(3ꢀ×ꢀ20ꢀml)ꢀandꢀbrineꢀonce.ꢀItꢀwasꢀdriedꢀ
(entryꢀ16).
Althoughꢀexcellentꢀresultsꢀwereꢀachievedꢀforꢀarylꢀiodidesꢀ
andꢀ arylꢀ bromides,ꢀ arylꢀ chloridesꢀ didꢀ notꢀ workꢀ veryꢀ wellꢀ
underꢀtheꢀstandardꢀconditions.ꢀItꢀwasꢀobservedꢀthatꢀtheꢀcross-
couplingꢀreactionꢀofꢀ4-chloroacetophenoneꢀwithꢀphenylboronicꢀ
overꢀanhydrousꢀMgSO , filtered, and concentrated. Preparative TLC
4
orꢀ columnꢀ chromatographyꢀ onꢀ silicaꢀ andꢀ elutionꢀ withꢀ petroleumꢀ
ether/EtOAcꢀ affordedꢀ theꢀ cross-couplingꢀ products.ꢀ Productsꢀ wereꢀ
acidꢀwasꢀlargelyꢀaffectedꢀbyꢀtheꢀratioꢀofꢀDMAꢀtoꢀH O.ꢀBothꢀ
1
13
2
confirmed by comparison of their HꢀNMRꢀandꢀ CꢀNMRꢀdataꢀwithꢀ
higherꢀ (DMA–H O,ꢀ 1ꢀ:ꢀ1)ꢀ andꢀ lowerꢀ (DMA–H O,ꢀ 20ꢀ:ꢀ1)ꢀ
thoseꢀreportedꢀinꢀtheꢀliterature.
2
2
1
6
16
waterꢀamountꢀhadꢀaꢀdeleteriousꢀeffectꢀonꢀcouplingꢀreaction,ꢀ
resultingꢀinꢀlowꢀyieldsꢀofꢀ4-acetylbiphenylꢀ(Tableꢀ3,ꢀentriesꢀ1ꢀ
and 7). Through fine tuning of the volumetric ratio of DMA to
4-Methoxybiphenyl (Table 2, entry 1): ꢀꢀ M.p.ꢀ 90–91ꢀ°Cꢀ (Lit. ꢀ
7–88ꢀ°C).ꢀ HꢀNMRꢀ(400ꢀMHz,ꢀCDCl ): δ 7.55 (t, Jꢀ=ꢀ8.8ꢀHz,ꢀ4H),ꢀ
1
8
7
2
1
3
.42ꢀ(t, Jꢀ=ꢀ8ꢀHz,ꢀ2H),ꢀ7.31ꢀ(t,ꢀJꢀ=ꢀ7.2ꢀHz,ꢀ1H),ꢀ6.99ꢀ(d,ꢀJ =ꢀ8.4ꢀHz,ꢀ
1
3
H),ꢀ3.86ꢀ(s,ꢀ3H);ꢀ CꢀNMRꢀ(100ꢀMHz,ꢀCDCl ): δ 159.12, 140.81,
3
H O,ꢀtheꢀratioꢀofꢀ5ꢀ:ꢀ1ꢀwasꢀfoundꢀtoꢀbeꢀtheꢀbestꢀvalueꢀ(entriesꢀ
2
33.76,ꢀ128.69,ꢀ128.14,ꢀ126.70,ꢀ126.64,ꢀ114.18,ꢀ55.32.
2
–6)ꢀsinceꢀtheꢀhighestꢀyieldꢀofꢀ4-acetylbiphenylꢀ(77%)ꢀwasꢀ
17
17
2
-Nitrobiphenyl (Table 2, entry 2): ꢀ M.p.ꢀ 37–38ꢀ°Cꢀ (Lit. ꢀ 34–
1
achievedꢀinꢀthisꢀsolventꢀsystemꢀ(entryꢀ3).
35ꢀ°C).ꢀ Hꢀ NMRꢀ (400ꢀ MHz,ꢀ CDCl ): δ 7.86 (d, Jꢀ =ꢀ 8.0ꢀ Hz,ꢀ 1H),ꢀ
3
1
3
Variousꢀ arylꢀ chloridesꢀ withꢀ electron-withdrawnꢀ groupsꢀ
couldꢀbeꢀcoupledꢀwithꢀphenylboronicꢀacidꢀinꢀtheꢀsameꢀsolventꢀ
systemꢀ providingꢀ 78–97%ꢀ yieldsꢀ ofꢀ desiredꢀ cross-couplingꢀ
productsꢀ (Tableꢀ 4,ꢀ entriesꢀ 1–4).ꢀ However,ꢀ 4-chlorotoluene,ꢀ
anꢀelectron-neutralꢀarylꢀchloride,ꢀgaveꢀonlyꢀmoderateꢀyieldꢀofꢀ
7.62ꢀ(t, Jꢀ=ꢀ7.2ꢀHz,ꢀ1H),ꢀ7.51–7.40ꢀ(m,ꢀ5H),ꢀ7.34–7.31ꢀ(m,ꢀ2H);ꢀ Cꢀ
NMRꢀ(100ꢀMHz,ꢀCDCl ): δ 149.12, 137.26, 136.10, 132.15, 131.78,
3
1
1
6
16
1
HꢀNMRꢀ(400ꢀMHz,ꢀCDCl ): δ 7.58 (d, Jꢀ=ꢀ7.6ꢀHz,ꢀ2H),ꢀ7.55ꢀ(d,
Jꢀ=ꢀ8.1ꢀHz,ꢀ2H),ꢀ7.48ꢀ(t,ꢀJꢀ=ꢀ7.5ꢀHz,ꢀ2H),ꢀ7.33ꢀ(d,ꢀJꢀ=ꢀ7.2ꢀHz,ꢀ1H),ꢀ
1
3
4-methylbiphenylꢀ(entryꢀ5).ꢀThus,ꢀcomparedꢀwithꢀtheꢀoptimalꢀ
7.25ꢀ(d,ꢀJꢀ=ꢀ6.0ꢀHz,ꢀ2H),ꢀ2.40ꢀ(s,ꢀ3H);ꢀ CꢀNMRꢀ(100ꢀMHz,ꢀCDCl3)ꢀ:ꢀ
δ 141.13, 138.32, 136.95, 129.44, 128.68, 127.13, 126.94, 21.05.
reactionꢀ systemꢀ forꢀ arylꢀ bromidesꢀ (Schemeꢀ 1),ꢀ changesꢀ inꢀ
1
6
16
4
-Cyanobiphenyl (Table 2, entry 4): ꢀM.p.ꢀ86–87ꢀ°Cꢀ(Lit. ꢀ88–
catalystꢀloading,ꢀtemperatureꢀandꢀvolumetricꢀratioꢀofꢀDMA–H Oꢀ
2
1
8
9ꢀ°C).ꢀ HꢀNMRꢀ(400ꢀMHz,ꢀCDCl ): δ 7.73 (d, J =ꢀ7.6ꢀHz,ꢀ2H),ꢀ7.69ꢀ
3
madeꢀthisꢀcatalyticꢀsystemꢀapplicableꢀtoꢀactivatedꢀarylꢀchlorides.
Inꢀsummary,ꢀaꢀconvenientꢀprotocolꢀhasꢀbeenꢀdevelopedꢀforꢀ
(d, J =ꢀ8.4,ꢀ2H),ꢀ7.59ꢀ(d,ꢀJ =ꢀ8.0ꢀHz,ꢀ2H),ꢀ7.49ꢀ(t,ꢀJ =ꢀ8.0ꢀHz,ꢀ2H),ꢀ
13
7
.47–7.41ꢀ(m,ꢀ1H).ꢀ CꢀNMRꢀ(100ꢀMHz,ꢀCDCl ): δ 145.53, 139.03,
3
theꢀ ligandlessꢀ Pd(OAc) -catalysedꢀ Suzuki–Miyauraꢀ reactionꢀ
132.49,ꢀ129.02,ꢀ128.57,ꢀ127.62,ꢀ127.13,ꢀ118.87,ꢀ110.78.
2
1
6
ofꢀ arylꢀ halidesꢀ withꢀ arylboronicꢀ acidsꢀ inꢀ aqueousꢀ DMAꢀ inꢀ
airꢀ withoutꢀ theꢀ aidꢀ ofꢀ phase-transferꢀ reagent.ꢀ Thisꢀ protocolꢀ
allows the efficient coupling of various aryl bromides with
arylboronicꢀacidsꢀatꢀroomꢀtemperatureꢀinꢀaꢀquiteꢀshortꢀreactionꢀ
Biphenyl-4-carbaldehyde (Table 2, entry 6) ꢀ:ꢀꢀ M.p.ꢀ 57–58ꢀ°Cꢀ
1
6
1
(
Lit. ꢀ59ꢀ°C).ꢀ HꢀNMRꢀ(400ꢀMHz,ꢀCDCl ): δ 10.07 (s, 1H), 7.96 (d,
3
J =ꢀ8.0ꢀHz,ꢀ2H),ꢀ7.76ꢀ(d,ꢀJ =ꢀ8.0ꢀHz,ꢀ2H),ꢀ7.64ꢀ(d,ꢀJ =ꢀ8.0ꢀHz,ꢀ2H),ꢀ
1
3
7
1
.51-7.42ꢀ(m,ꢀ3H);ꢀ CꢀNMRꢀ(100ꢀMHz,ꢀCDCl ): δ 191.87, 147.14,
3
39.66,ꢀ135.15,ꢀ130.23,ꢀ128.69,ꢀ128.42,ꢀ127.63,ꢀ127.32.
times.ꢀAꢀstrongꢀsolventꢀeffectꢀwasꢀobservedꢀandꢀDMA–H Oꢀ
Biphenyl-4-ol (Table 2, entry 7):18ꢀM.p.ꢀ159–161ꢀ°Cꢀ(Lit.18ꢀ164–
2
1
(5ꢀ:ꢀ1)ꢀ wasꢀ foundꢀ toꢀ beꢀ theꢀ bestꢀ solventꢀ system,ꢀ inꢀ whichꢀ
165ꢀ°C).ꢀ HꢀNMRꢀ(400ꢀMHz,ꢀCDCl3): δ 7.54 (d, J =ꢀ8.0ꢀHz,ꢀ2H),ꢀ
7
2
.49ꢀ(d,ꢀJ =ꢀ8.0ꢀHz,ꢀ2H),ꢀ7.42ꢀ(t,ꢀJ =ꢀ8.0ꢀHz,ꢀ2H),ꢀ7.32ꢀ(d,ꢀJ =ꢀ7.2ꢀHz,ꢀ
H),ꢀ 6.91ꢀ (d,ꢀ J =ꢀ 7.2ꢀ Hz,ꢀ 2H);ꢀ Cꢀ NMRꢀ (100ꢀ MHz,ꢀ CDCl )ꢀ:ꢀꢀ
activated aryl chlorides were efficiently coupled to provide
theꢀcross-couplingꢀproductsꢀinꢀgoodꢀtoꢀexcellentꢀyields.
1
3
3
δ 155.00, 140.73, 134.07, 129.40, 128.71, 128.39, 126.71, 115.62.
1
9
N-biphenyl-4-yl-acetamide (Table 2, entry 8): ꢀM.p.ꢀ167–169ꢀ°Cꢀ
Lit. ꢀ168–170ꢀ°C).ꢀ HꢀNMRꢀ(400ꢀMHz,ꢀCDCl ): δ 7.57–7.54 (m,
Experimental
1
9
1
(
3
Allꢀ reagentsꢀ wereꢀ purchasedꢀ fromꢀ commercialꢀ suppliersꢀ andꢀ usedꢀ
6
2
1
H),ꢀ7.43ꢀ(t, J =ꢀ7.6ꢀHz,ꢀ2H),ꢀ7.33ꢀ(t,ꢀJ =ꢀ7.2ꢀHz,ꢀ1H),ꢀ7.20ꢀ(s,ꢀ1H),ꢀ
without further purification. All solvents were distilled before use.
13
.22ꢀ(s,ꢀ3H);ꢀ CꢀNMRꢀ(100ꢀMHz,ꢀCDCl ) δ 168.73, 140.70, 137.41,
3
1
13 ꢀ
Theꢀ HꢀNMRꢀspectraꢀwereꢀrecordedꢀatꢀ300ꢀMHzꢀorꢀ400ꢀMHzꢀandꢀ C
35.86,ꢀ128.99,ꢀ127.80,ꢀ127.32,ꢀ127.04,ꢀ120.50,ꢀ24.82.
NMRꢀspectraꢀwereꢀmeasuredꢀatꢀ75ꢀMHzꢀorꢀ100ꢀMHz,ꢀusingꢀCDCl3,ꢀ
16
16
4-Nitrobiphenyl (Table 2, entry 9): ꢀ M.p.ꢀ 112–113ꢀ°Cꢀ (Lit. ꢀ
acetone-d ,ꢀDMSO-d asꢀtheꢀsolvents.
113ꢀ°C).ꢀ1HꢀNMRꢀ(400ꢀMHz,ꢀCDCl ): δ 8.31 (d, Jꢀ=ꢀ8.4ꢀHz,ꢀ2H),ꢀ
6
6ꢀ
3
7
.75ꢀ(d,ꢀJꢀ=ꢀ8.8ꢀHz,ꢀ2H),ꢀ7.63ꢀ(d,ꢀJꢀ=ꢀ7.6ꢀHz,ꢀ2H),ꢀ7.51–7.47ꢀ(m,ꢀ
Table 3ꢀ EffectꢀofꢀDMA–H Oꢀvolumetricꢀratioꢀonꢀcross-couplingꢀ
2
a
reactionꢀofꢀ4-chloroacetophenoneꢀwithꢀphenylboronicꢀacid
Table 4ꢀ Suzuki–Miyauraꢀ couplingꢀ ofꢀ arylꢀ chloridesꢀ withꢀ
phenylboronicꢀacidꢀinꢀaqueousꢀDMAa
Cl
Pd(OAc)
2
(2 mol %)
(2 equiv)
PhB(OH)
1.5 equiv
2
+
Pd(OAc)
2
(2 mol %)
O (2 equiv)
O=5:1(6 mL)
K
3
PO ·3H
4
2
O
Cl
PhB(OH)2
Ac
+
R
K
PO ·3H
R
DMA / H O (6 mL)
C, 24 h, air
2
3
4
2
Ac
1.5 equiv
o
80
DMA/H
2
o
80
C, 24 h, air
Entryꢀ
DMA/H Oꢀ
Yield/%bꢀ
Conversion/%
2
Entryꢀ
1ꢀ
Rꢀ
Yield/)bꢀ
Conversion/%
1
2
3
4
5
6
7
a
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
1ꢀ: ꢀ1 ꢀ
4ꢀ: ꢀ1 ꢀ
23ꢀ
40ꢀ
77ꢀ
47ꢀ
39ꢀ
29ꢀ
20ꢀ
30
52
80
53
48
31
23
4-NO2ꢀ
4-Acꢀ
4-CNꢀ
4-CF3ꢀ
4-Meꢀ
97ꢀꢀ
77ꢀꢀ
87ꢀꢀ
78ꢀꢀ
50ꢀꢀ
99
80
c
5ꢀ: ꢀ1 ꢀ
2 ꢀ
6ꢀ: ꢀ1 ꢀ
3ꢀ
4ꢀ
5ꢀ
93
10ꢀ: ꢀ1 ꢀ
15ꢀ: ꢀ1 ꢀ
20ꢀ: ꢀ1 ꢀ
100
65
a
Unlessꢀ otherwiseꢀ indicated,ꢀ allꢀ reactionsꢀ wereꢀ performedꢀ
b
c
Unlessꢀotherwiseꢀindicated,ꢀallꢀreactionsꢀwereꢀperformedꢀwithꢀ
withꢀ1.0ꢀmmolꢀofꢀarylꢀchlorides.ꢀ Isolatedꢀyield.ꢀ Biphenylꢀwasꢀ
obtainedꢀinꢀtheꢀyieldꢀofꢀ36%.
b
1
.0ꢀmmolꢀofꢀ4-chloroacetophenone.ꢀ Isolatedꢀyield.

JOURNALꢀOFꢀCHEMICALꢀRESEARCHꢀ2008ꢀ 527
13
7.42 (d, J = 6.0 Hz, 1H), 2.65 (s, 3H); 13CꢀNMRꢀ(100ꢀMHz,ꢀCDCl )ꢀ:ꢀ
3
H);ꢀ CꢀNMRꢀ(100ꢀMHz,ꢀCDCl ): δ 147.56, 147.02, 138.69, 129.11,
3
3
1
28.87, 127.74, 127.32, 124.03.
δ 197.61, 145.62, 139.72, 135.72, 128.86, 128.81, 128.14, 127.16,
127.10, 26.56.
2
0
Biphenyl-4-carboxylic acid ethyl ester (Table 2, entry 10): M.p.
5–46ꢀ°C (Lit.20 47–48ꢀ°C). H NMR (400 MHz, CDCl ): δ 8.11 (d,ꢀ
1
20
4
4-Trifluoromethylbiphenyl (Table 4, entry 4) : M.p. 69–70ꢀ°Cꢀ
3
J = 8.4 Hz, 2H), 7.67–7.64 (m, 4H), 7.47 (t, J = 7.4 Hz, 2H), 7.40 (d,
J = 7.2 Hz, 2H), 4.40 (q, J = 7.2 Hz, 2H), 1.42 (t, J = 7.2 Hz, 3H);ꢀ
(Lit.20 64–65ꢀ°C). 1H NMR (400 MHz, CDCl ): δ 7.69 (s, 4H), 7.60
3
(
d, J = 7.6 Hz, 2H), 7.48 (t, J = 7.6 Hz, 2H), 7.40 (t, J = 7.6 Hz,
1
3
Cꢀ NMRꢀ (100ꢀ MHz,ꢀ CDCl ): δ 166.47, 145.47, 140.00, 130.02,
13
3
1H);ꢀ ꢀCꢀNMRꢀ(100ꢀMHz,ꢀCDCl ) δ 144.71, 139.73, 129.17, 128.96,
3
1
29.20, 128.87, 128.06, 127.23, 126.96, 60.93, 14.34.
1
28.17, 127.38, 127.24, 125.70, 125.66.
2
1
4
'-Methoxy-4-methylbiphenyl (Table 2, entry 11): M.p. 110–
12ꢀ°C (Lit. 109–110ꢀ°C). 1H NMR (400 MHz, CDCl ): δ 7.51ꢀ
21
1
3
This work was supported by the National Natural Science
Foundation of China (No. 20572046 and No. 20421202),
the 111 Project (B06005), and the Ministry of Educationꢀ
of China.
(d, J = 8.8 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H),
1
3
6
.967 (d, J = 8.8 Hz, 2H), 3.85 (s, 3H), 2.38 (s, 3H); CꢀNMRꢀ(100ꢀ
MHz,ꢀ CDCl ): δ 158.88, 137.90, 136.29, 133.67, 129.40, 127.90,
1
3
26.53, 114.11, 55.23, 21.01.
Biphenyl-4-carboxylic acid (Table 2, entry 12): M.p. 225–227ꢀ°Cꢀ
1
8
18
1
(Lit. 227–229ꢀ°C). H NMR (400 MHz, DMSO-d ): δ 12.99 (bs,
6
Received 29 May 2008; accepted 31 July 2008
Paper 08/5300 doiꢀ:ꢀ10.3184/030823408X349952
Published online: 5 September 2008
1
H), 8.02 (d, J = 8.0, 2H), 7.80 (d, J = 8.0 Hz, 2H), 7.73 (d, J = 7.2
1
3
Hz, 2H), 7.50 (t, J = 7.2 Hz, 2H), 7.43 (d, J = 7.2 Hz, 1H); CꢀNMRꢀ
100 MHz, DMSO-d ): δ 167.50, 144.57, 139.22, 130.25, 129.82,
(
6
1
29.29, 128.48, 127.14, 127.00
Biphenyl-3-carboxylic acid (Table 2, entry 13): M.p. 165–167ꢀ°Cꢀ
1
8
References
18
1
(Lit. 163–166ꢀ°C). H NMR (300 MHz, Acetone-d ): δ 11.39 (bs,
6
1
2
3
N. Miyaura, T. Yanagi and A. Suzuki, Synth. Commun., 1981, 11, 513.
F. Bellina, A. Carpita and R. Rossi, Synthesis, 2004, 2419.
J.P. Wolfe, R.A. Singer, B.H. Yang and S.L. Buchwald, J. Am. Chem. Soc.,ꢀ
1999, 121, 9550.
1
7
2
H), 8.30 (s, 1H), 8.05 (d, J = 7.2 Hz, 1H), 7.93 (d, J = 7.8 Hz, 1H),
.72 (d, J = 7.2 Hz, 2H), 7.62 (t, J = 7.2 Hz, 1H), 7.51 (t, J = 7.2 Hz,
1
3
H), 7.42 (t, J = 7.2 Hz, 1H); C NMR (75.5 MHz, Acetone-d )ꢀ:ꢀ
6
δ 206.12, 167.52, 142.25, 140.90, 132.22, 130.03, 129.90, 129.32,
28.79, 128.69, 127.84.
-Methoxy-4'-methylbiphenyl (Table 2, entry 14): M.p. 70–72ꢀ°Cꢀ
4
5
A.F. Littke, C. Dai and G.C. Fu, J. Am. Chem. Soc., 2000, 122, 4020.
T. Migita, T. Nagai, K. Kiuchi and M. Kosugi, Bull. Chem. Soc. Jpn.,
1983, 56, 2869.
K.-C. Kong and C.-H. Cheng, J. Am. Chem. Soc., 1991, 113, 6313.
T.I. Wallow and B.M. Novak, J. Org. Chem., 1994, 59, 5034.
N.A. Bumagin and V.V. Bykov, Tetrahedron, 1997, 62, 14437.
E.M. Campi, W.R. Jackson, S.M. Marcuccio and C.G.M. Naeslund,
Chem. Commun., 1994, 2395.
1
3
2
3
1
6
7
8
9
(
Lit. 71–72ꢀ°C). H NMR (400 MHz, CDCl ): δ 7.42 (d, J = 8.0 Hz,
3
2
3
1
H), 7.32–7.29 (m, 2H), 7.22 (t, J = 7.4 Hz, 2H), 7.03–6.96 (m, 2H),
.80 (s, 3H), 2.39 (s, 3H); 13CꢀNMRꢀ(100ꢀMHz,ꢀCDCl ): δ 156.42,
3
36.50, 135.53, 130.72, 130.61, 129.34, 128.67, 128.30, 120.72,
1
11.09, 55.42, 21.14.
4
1
0
L. Liu, Y. Zhang and Y. Wang, J. Org. Chem.,ꢀ2005,ꢀ70, 6122.
L. Liu, Y. Zhang and B. Xin, J. Org. Chem., 2006, 71, 3994.
-Methoxy-2-methylbiphenyl (Table 2, entry 15):22 Colourless oil.
1
1
1
H NMR (400 MHz, CDCl ): δ 7.32 (d, J = 6.8 Hz, 2H), 7.26–7.19
3
12 D. Badone, M. Baroni, R. Cardamore, A. Ielmini and U. Guzii, J. Org.
Chem., 1997, 62, 7170.
13 D. Zim, A. Monteiro and J. Dupont, Tetrahedron Lett., 2000, 41, 8199.
14 Y. Deng, L. Gong, A. Mi, H. Liu and Y. Jiang, Synthesis, 2003, 337.
15 X. Tao, Y. Zhao and D. Shen, Synlett, 2004, 359.
16 J. Li, Y. Huang and M. Cai, J. Chem. Res., 2006, 658.
17 D.A. Widdowson and R. Wilhelm, Chem. Commun., 2003, 578.
18 G. Lu, R. Franzén, Q. Zhang and Y. Xu, Tetrahedron Lett., 2005,
(
3
m, 3H), 7.09 (d, J = 8.4 Hz, 1H), 6.74 (s, 2H), 3.77 (s, 3H), 2.20 (s,
13
H);ꢀ CꢀNMRꢀ(100ꢀMHz,ꢀCDCl ): δ 158.67, 141.58, 136.59, 134.53,
3
1
30.74, 129.32, 127.94, 126.38, 115.65, 111.00, 55.07, 20.67.
23
2
-Methoxy-2'-methylbiphenyl (Table 2, entry 16): M.p. 41–43 ꢀ° Cꢀ
23
1
(Lit. 42–44 ꢀ° C). H NMR (400 MHz, CDCl ): δ 7.35 (t, J = 7.2 Hz,
3
1
H), 7.26–7.14 (m, 5H), 7.03–6.96 (m, 2H), 3.77 (s, 3H), 2.14 (s, 3H);
1
3
CꢀNMRꢀ(100ꢀMHz,ꢀCDCl ): δ 155.54, 138.60, 136.75, 130.94, 130.79,
3
4
6, 4255.
1
29.96, 129.52, 128.51, 127.24, 125.40, 120.39, 110.59, 55.30, 19.88.
2
-Methylbiphenyl (Table 2, entry 17):11 Colourless oil. Hꢀ NMRꢀ
1
19 S. Srivastava, P.H. Ruane, J.P. Toscano, M.B. Sullivan, C.J. Cramer,ꢀ
D. Chiapperino, E.C. Reed and D.E. Falvey, J. Am. Chem. Soc.,ꢀ2000,ꢀ
(
400 MHz, CDCl ): δ 7.39–7.36 (m, 3H), 7.34–7.25 (m, 2H), 7.20–
3
1
22, 8271.
A.K. Sahoo, T. Oda, Y. Nakao and T. Hiyama, Adv. Synth. Catal., 2004,
46, 1715.
S.E. Denmark and M.H. Ober, Org. Lett.,ꢀ2003,ꢀ5, 1357.
13
7
1
1
.17 (m, 4H), 2.20 (s, 3H); CꢀNMRꢀ(100ꢀMHz,ꢀCDCl ): δ 141.90,
3
2
2
0
1
41.88, 135.23, 130.27, 129.76, 129.14, 128.02, 127.21, 126.71,
25.74, 20.42.
3
4
-Acetylbiphenyl (Table 4, entry 2): M.p. 120–121ꢀ°C (Lit.16ꢀ
16
22 L.R. Moore and K.H. Shaughnessy, Org. Lett., 2004, 6, 225.
23 T.E. Barder, S.D. Walker, J.R. Martinelli and S.L. Buchwald, J. Am.
Chem. Soc.,ꢀ2005,ꢀ127, 4685.
1
1
17–118ꢀ°C). H NMR (400 MHz, CDCl ): δ 8.04 (d, J = 6.4 Hz,
3
2
H), 7.70 (d, J = 6.8 Hz, 2H), 7.64 (d, J = 5.2 Hz, 2H), 7.48 (m, 2H),