Communication
Bipyridine-Modulated Palladium-catalyzed Oxidative Heck-type Reactions
of Arylboronic Acids with Olefins
Chien-Ming Hsu(),Chih-Bin Li()and Chia-Hsing Sun*()
Department of Chemistry,Soochow University,Taipei111,Taiwan,R.O.C.
We have demonstrated that4,4¢-dimethyl2,2¢-bipyridine as ligand for Pd(II)catalysts was very effi-cient for oxidative Heck-type coupling reaction of arylboronic acids with olefins in DMA or CH3CN un-der atm air at80°C.The prence of chelated bipyridine ligand isindispensable to achieve high reaction yields and to suppress the formation of biphenyl as homocoupled byproduct.
Keywords:Bipyridine-modulated;4,4¢-Dimethyl2,2¢-bipyridine;Pd(II)catalysts;Oxidative Heck-type coupling reaction;Arylboronic acids;Olefins.
INTRODUCTION
The transition metal-catalyzed cross-coupling reac-tion of organoboronic acid and olefins,known as the oxida-tive Heck reactions,1is now growing rapidly as one of the alternative tools for constructing C-C bonds,mainly be-cau boronic acids are stable,low toxic,and commercially available.2Palladium-catalyzed oxidative Heck reactions3 have been extensively investigated by veral rearch groups including Larhed.’s in which a typical oxidative Heck experiments was investigated in acetonitrile using. p-Tolylboronic acid n-butyl acrylate N-methylmorpholine (NMM)as ba,ligand and2%Pd(OAc)2as the palladium source.1d They found phenanthroline-class ligand,espe-cially2,9-dimthyl-1,10-phenanthroline(dmphen)ligand provided high yields with good control over the regio-chemistry and stereochemistry under open-air and at room temperature.1d Other nitrogen-containing ligands such as momodentate pyridine was ineffective,and both2,2¢-bi-pyridine and6,6¢-dimethyl-2,2¢-bipyridine gave modest production with Pd black formation for the latter.Generally nitrogen-containing ligands,known to facilitate the reoxi-dation of Pd(0)and stabilize Pd(II)complex thus formed, are very cheap,air and moisture stable compared to their phosphine counterparts.4Nitrogen-containing ligands have been found most successful when the reaction is run under oxygen.1Although the mechanistic aspect of the reaction is not well-elucidated yet,bad on the standpoint of better understanding and control of oxidative Heck reactions and their synthetic applications,it is intriguing to promote bi-pyridine ligands for oxidative Heck reactions since bipyri-din
e ligands required are either commercially-available or synthetically accessible.Herein we reported that4,4¢-di-methyl-2,2¢-bipyridine1c was screened as the most supe-rior ligand for for Pd(II)catalysts,it was very efficient for oxidative Heck-type coupling reaction of arylboronic acids with olefins in DMA or CH3CN under atm air at80°C in high yields and without biphenyl as homo-coupled byprod-uct.
RESULTS AND DISCUSSION
As illustrated in Table1,veral commercially avail-able pyridine(1a)and bipyridine derivatives(1b-1k,ex-cept1f and1j were prepared)were screened as potential ligands,using a model cross-coupling reaction1.0mmol of butyl acrylate and2.0mmol of phenylboronic acid in the prence of2mol%of Pd(OAc)2,2.4mol%of ligand and 2.0mmol of N-methylmorpholine(NMM)in5.0mL of DMA at80°C in atm air.Ligand was found to be a crucial factor in determining the yields of product3a and biphenyl, a homocoupled byproduct.Without ligand,only2%of3a was produced with18%of biphenyl isolated as the major product(entry1).Pyridine,a monodentate nitrogen ligand did not work either.Among bidentate nitrogen ligands, 4,4¢-dimethyl-2,2¢-bipyridine1c proved to be the most su-perior one to give3a in96%yields,while6,6¢-dimethyl-2,2¢-bipyridine1i gave considerably lower yields of38%
Journal of the Chine Chemical Society,2009,56,873-880873
*Corresponding author.E-mail:
chsun@mail.scu.edu.tw
and significant amount of biphenyl as homocoupled by-product due to the steric hindrance of dimethyl at 6,6¢-posi-tion of bipyridyl (entry 10).Stronger electron-donating methoxy group,at 4,4¢-position,did not improve but re-sulted in lower reaction yields (entry 5)and at 6,6¢-posi-tion,gave very low yield of 11%(entry 11).Even lower re-action yields of 51%were obtained with electron-with-drawing groups –COOH (entry 8),-COOMe (entry 9)and poor yield of 11%with the strongest electron-withdrawing group –CF 3(entry 7).Slight electron-withdrawing phenyl group,at 4,4¢-position,gave moderate yield of 75%(entry 6),but poor yield of 11%at 6,6¢-position (entry 12).When increasing ligand 1c from 2.4mol%to 4.5mol%,it resulted in a yield decrea of 3a by 11%.From our obrvation,it may suggest that dimethyl group at 4,4¢-position (1c )of bipyridyl will give a tight biden
tate-Pd coordination bond-ing which afforded a stable Pd complex with higher cata-lytic activity.However,dimethoxyl group at 4,4¢-positoin (1d )of bipyridyl will give a stronger bonding to inhibit the catalytic activity of Pd complex.It is also clear that weaker coordination bonding between N-Pd-N will lead to low re-action efficacy as electron-withdrawng groups were at-tached at 4,4¢-positoin (1d )of bipyridyl.Generally,steric hindrance impod by substituents at 6,6¢-position of bi-pyridyl will destabilize the Pd complex and lower the cata-lytic activity.The prence of chelated bipyridine ligand is indispensable to achieve high reaction yields and to sup-press the formation of biphenyl as homocoupled byprod-uct.
To optimize the reaction condition,solvents were found to have profound effect on palladium catalytic activ-ity (Table 2).Attempts on optimization with respect to sol-vent showed that the reaction proceeded best in DMA (96%),Other aprotic polar solvents such as acetonitrile,DMF and DMSO,except NMP,proved to be effective also with no more than 90%yields.The nopolar solvents such as dioxane and toluene gave lower yields.Notably,both electronic effect and steric effect were pronounced for sub-stituted arylboronic acids.Generally,electron-donating arylboronic acids with MeO-or Me-at 4-position (entry 2and entry 3)gave significantly higher yields than tho of electron-withdrawing arylboronic acids with Me(C=O)-or CF 3-at 4-position (entry 5and entry 7)and NO 2-at 3-
posi-tion (entry 10).Steric hindrance was found to decrea sig-nificantly the reaction yields at 2-position (entry 4and en-try 9).But unsubstituted arylboronic acid (entry 1)af-
874J.Chin.Chem.Soc.,Vol.56,No.5,2009Hsu et al.
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Table 1.Ligand screenig on oxidative arylation of n -butyl
生活大爆炸第二季1acrylate with phenylboronic acid
a
3a
mylf是什么意思Entry Ligand Yield (%)b
Yield of biphenyl (%)b 1No L
21821a N
113
番禺会计培训机构1b
N N
51
141c
N
N
966c 85d
10c 1d 51d
N
N
OCH 3
H 3CO
南宁会计培训
88
1
61e
N
N
Ar
Ar
75
1
71f
N
N
CF 3
F 3C
11
1
马达加斯加1下载81g
N
N
COOH
HOOC
51
上海新世界日语3
91h
N
N
COOCH 3
H 3COOC
512101i
N N
3839c 720c 111j
N N
OCH 3
H 3CO
11
1
12
1k N N
Ar
Ar
111
a
Reaction conditions:1.0mmol of olefin,2.0mmol of boronic acid,2mol%of Pd(OAc)2,2.4mol%of ligand,2.0mmol of NMM,5.0mL of DMA.b
Isolated yield.c
Performed at rt,5.0mL of CH 3CN.d
4.5mmol%Ligand.
forded the highest yields than the substituted ones.Unex-pectedly,electron-releasing 4-butyl diminished while elec-tron-withdrawing 4-fluoro enhanced the reaction yields.
In a typical reaction mechanism propod for Heck-type coupling reaction,aryl group is transferred to bipyri-dine palladium(II)intermediate to form an aryl palladium complex (Scheme I).Presumably,the reactivity of bipyri-dine aryl-Pd complex is determined by a resultant elec-tronic balance on p -donating and p -accepting ability of sub-stituent on aryl ring.Electron-donating group will increa p -donating ability,meanwhile decrea its p -accepting ability of aryl ring,and rever are the electron-withdraw-ing groups.
The open vesl procedure employing 6,6¢-dimethyl-2,2¢-bipyridine 1i was thereafter applied directl
y to a range of olefins (4a -f ),utilizing phenylboronic acid (2a )as the arylating agent (Table 4).Both electron-poor and elec-tron-rich olefins were coupled in moderate to good yields.
Bipyridine-Modulated Heck-type Reactions J.Chin.Chem.Soc.,Vol.56,No.5,2009
875
Scheme I Propod mechanism for Heck-type oxidative arylation of olefins
Table 2.Solvent effect on oxidative arylation of n -butyl acrylate
with phenylboronic acid
a
2mmol%Pd(OAc)2
Entry Solvent Yield (%)b
1CH 3CN 902DMF 913DMA 964DMSO 925NMP 636Dioxane 617
Toluene
61
a
Reaction conditions:1.0mmol of olefin,2.0mmol of boronic acid,2.0mmol of NMM,5.0mL of solvent.b
Isolated yield.
The high reactivity of both electron-poor 4a and 4c pro-duced excellent yields (93%and 88%)after 24h at 80°C (entry 1and entry 3,Table 4)with high regiolectivity (99%)at b -position.The electron-rich olefin (4d )gave lower yield (68%)with high regiolectivity at a -position.Surprisingly styrene (4b )only afforded low yield (36%)in DMA and high yield (93%)in acetonitrile with slightly lower regiolectivity.
A comparison is made in Table 5on chelated biden-tate 4,4¢-dimethyl 2,2¢-bipyridine and 2,9-dimethyl-1,10-phenanthroline as ligand in Heck-type reaction.2,9-di-methyl-1,10-phenanthroline was reported as a superior ligand in which the reaction was performed at room tem-perature to give 81%yield and high regiolectivity in ace-
tonitrile with butyl acrylate (entry 1),and 85%yield with styrene (entry 2).Importantly,4,4¢-dimethyl 2,2¢-bipyri-dine performed better at higher temperature 80°C to give 96%yield with butyl acrylate in
DMA (entry 3),and 93%yield with styrene in acetonitrile (entry 4).Both reactions also afforded high regiolectivities.
In conclusion,we have demonstrated that 4,4¢-dimeth-yl 2,2¢-bipyridine as ligand for Pd(II)catalysts was very ef-ficient for oxidative Heck-type coupling reaction of aryl-boronic acids with olefins in DMA or CH 3CN under atm air at 80°C.The prence of chelated bipyridine ligand is in-dispensable to achieve high reaction yields and to suppress the formation of biphenyl as homocoupled byproduct.The catalytic activity was found nsitive to both electronic and steric effect of substituents on the 2,2¢-bipyridine.Elec-tron-withdrawing groups and steric hindrance will retard the reaction,while the electron-donating groups will en-hance it.However,too strong electron-donating group such as methoxy group will result in lower yield than moderate electron-donating group such as methyl group.
876J.Chin.Chem.Soc.,Vol.56,No.5,2009Hsu et al.
Table 3.Oxidative arylation of n -butyl acrylate with diver
arylboronic acid a Entry Boronic acid
Products &Yield
(%)b
12a B(O H)2
3a ,96
c
22b B(O H)2
H 3CO
3b ,90c 3
2c
B(OH)2
H 3Clike this
3c ,86
42d
B(O H)2
CH 3
3d ,32
一年级数学思维训练c
52e B(OH )2
H 3CO C
3e ,6862f B(OH)2F 3f ,8472g B(OH)2
F 3C
3g ,35c 8
2h
B(OH)2
n-Bu
turn the corner
3h ,33
92i
B(OH)2
OCH 3
3i ,29
10
2j
B(OH)2
O 2N
3j ,24
a
Reaction conditions:1.0mmol of olefin,2.0mmol of boronic acid,2.0mmol of NMM,5.0mL of DMA.b
Isolated yield.c
Determined by NMR,a /b =1/99.
Table 4.Oxidative arylation of different olefins with phenyl-boronic acid a
R +
B(OH)
2mmol%Pd(OAc)2
DMA,NMM,Air,80C,24h
R
Entry Olefin
Product &Yield
(%)b
a
/b d 1
4a
O
OBu
3a ,96
1/9924b
5b ,365b ,93c 2/985/9534c
N
CH 3CH 35c ,88
1/99
44d N O 5d ,6899/1
a
Reaction conditions:1.0mmol of olefin,2.0mmol of boronic acid,2.0mmol of NMM,5.0mL of DMA.b
Isolated yield.c
Solvent is CH 3CN.d
Determined by NMR.
EXPERIMENTAL
1H NMR(300MHz)and13C NMR(75MHz)spectra were recorded on a Bruker AVA-300spectrometer with TMS as internal standard.All reagents were ud directly as obtained commercially.All products are known. Typical experimental procedure for the palladium-catalyzed Heck-type cross-coupling reaction
Under an atmosphere of air,a mixture of Pd(OAc)2 (4.5mg,2.0mmol%),bipyridine(2.4mmol%),olefin(1.0 mmol),arylboronic acid(2.0mmol),NMM(2.0mmol)and DMA(5.0mL)were charged to a25mL round-buttom flask and stirred at80°C for24h.After ordinary workup and being evaporated by rotary evaporator,the residue was purified by column chromatography to give the required cross-coupled derivative(hexane/ethyl acetate).
Trans-stilbene(5b)7
White solid,mp=121-124°C;1H NMR(400MHz, CDCl3):d7.55(d,J=7.7Hz,4H,Ar),7.38(t,J=7.4Hz, 4H,Ar),7.31-7.27(m,2H,Ar),7.14(s,2H,ArC H C H Ar); 13C NMR(100MHz,CDCl
3
):d137.3,128.7,128.6,127.6, 126.
T rans-cinnamic acid n-butyl ester(3a)7Pale yellow liquid;1H NMR(300MHz,CDCl3):d7.68(d, J=16.2Hz,1H,ArC H),7.52-7.48(m,2H,Ar),7.37-7.34 (m,3H,Ar),6.43(d,J=15.9Hz,1H,C H CO2Bu),4.20(t,J =6.6Hz,2H,CO2C H2CH2),1.73-1.63(m,2H,CO2CH2C H2), 1.47-1.39(m,2H,C H2CH3),0.96(t,J=7.4Hz,3H, CH2C H3);13C NMR(75MHz,CDCl3):d166.9,144.4, 134.3,130.0,128.7,127.9,118.1,64.2,30.6,19.0,13.6. 4-Methoxy-trans-cinnamic acid n-butyl ester(3b)7
Pale yellow liquid;1H NMR(400MHz,CDCl3):d7.59(d, J=15.9Hz,1H,ArC H),7.42(d,J=8.8Hz,2H,Ar),6.85 (d,J=8.76Hz,2H,Ar),6.27(d,J=15.9Hz,1H, C H CO2Bu),4.16(t,J=6.7Hz,2H,CO2C H2CH2),3.77(s, 3H,ArOC H3),1.67-1.60(m,2H,CO2CH2C H2),1.42-1.36 (m,2H,C H2CH3),0.92(t,J=7.4Hz,3H,CH2C H3);13C NMR(100MHz,CDCl3):d167.3,161.2,144.1,129.5, 127.1,115.7,114.2,64.1,55.2,30.7,19.1,13.6.
4-Methyl-trans-cinnamic acid n-butyl ester(3c)7
Pale yellow liquid;1H NMR(300MHz,CDCl3):d7.65(d, J=16.0Hz,1H,ArC H),7.37(d,J=7.8Hz,2H,Ar),7.13 (d,J=7.8Hz,2H,Ar),6.37(d,J=16.2Hz,1H, C H CO2Bu),4.18(t,J=6.6Hz,
2H,CO2C H2CH2),2.32(s, 3H,ArC H3),1.68-1.61(m,2H,CO2CH2C H2),1.45-1.38
Bipyridine-Modulated Heck-type Reactions J.Chin.Chem.Soc.,Vol.56,No.5,2009877 Table5.Comparison of4,4¢-dimethyl2,2¢-bipyridine and2,9-dimethyl-1,10-phenanthroline
as ligand in Heck-type reaction
Entry11d Entry21d Entry3Entry4
Ligand
N N N N N N N N
Olefin
n Bu
O n Bu
Solvent CH3CN CH3CN DMA CH3CN Ba NMM NMM NMM NMM Temperature RT RT80°C80°C Time24h24h24h24h Yield81%85%96%93%
a/b0/100
15/85
1/99
5/95
