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Rhodium-Catalyzed Borylation of Aryl 2-Pyridyl Ethers through Cleavage of the Carbon–Oxygen Bond: Borylative Removal of the Directing Group J. Am. Chem. Soc., Ar%cle ASAP DOI: 10.1021/ja511622e James Johnson, Wipf Group Current Literature
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Transition Metal Catalyzed C-‐H bond transformations
Chem. Soc. Rev., 2011, 40, 5068–5083
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HR
[MLn]XR
YR2
R
Y = Sn, Cu, Ni, Zn, etc
R2
Traditional cross-coupling
[MLn]
YR2
R
R2[MLn]
HR2
Direct cross-coupling Dehydrogenative cross-coupling
[Ox]
HDG
R
C-H activation
HR
HH
Y = Br, I, M
HR
Substrate dependent
Angew. Chem. Int. Ed. 2012, 51, 10236 – 10254
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Common directing groups
HDG
[M]DG
FGDG
(Het)Ar (Het)Ar (Het)Ar
N N
NN N
O
NR
HN R
ON
ROMe CO2H OHn
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Adv Synth Catal. 2011, 8, 353
Directing groups in C-‐H activation
Angew. Chem. Int. Ed. 2011, 50, 2450 – 2494
NR
R
H
NR
R
ArAr-X removal of DG?
R
ArH
NSOO
NH
CO2Me
NH
CO2Me
B NHN N
HSiEt3RuH2(CO)(PPh3)3
1)
2) HCl aq., RT, 2h
R
B(OH)2
R
SiEt3
Pd(CH3CN)2Cl2
1)
2) Zn, NH4Cl THF RT
CO2H
R
Pd(OAc)2AgOAc/AcOH
ArI
RAr
H1)
2) CuO, 1,10-phenNMP, 160 °C 24h
OH
R
RhCl(PPh3)PR2OAr or PR2Cl
ArX
OH
R
Ar
toluene, reflux
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2-‐pyridylsilyl directing group
Pd(OAc)2PhI(OR)2AgOAcDCE
100 °C, 8 h22 examples
SiR N
DCE 70 °C, 1 h
24 examples
SiR N
X iPriPr
iPriPr
SiR N
iPriPr
SiR N
NX iPriPr
Pd(OAc)2PhI(OR)2
NXS
SiR N
iPriPr
OR
OR2) Pd(OAc)2, PhI(OR)2
AgOAc, DCE, 80°C, 20 h
1) Pd(OAc)2, PhI(OR)2NXS, DCE, 50°C, 12 hSi
R N
NiPriPr
21 examples
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Angew. Chem., Int. Ed. 2011, 50, 2450 Chem. Soc. Rev. 2014, 43, 6906. SynleQ 2013, 24, 145.
Removal of 2-‐pyridylsilyl group
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Chem. Soc. Rev. 2014, 43, 6906
2-‐Aminopyridine directing groups
NN
Pd(OAc)2AgNO3, BQ
tBuOH60°C, 24 h
ArBF3K
NN
Ar
24 examples
1) MeOTf, CH2Cl2rt, 24 h
2) NaOH, MeOHreflux, 12 h
HN Ar
ArNO2
OMe
80%
75%
70%
HNN
Pd(OAc)2Ag2O, BQ
THF80°C, 24 h
ArB(OH)2
HNN
Ar
15 examplesR R
1) Pd/C, H2, HCliPrOH, rt, 16 h
2) NH2NH2 AcOHiPrOH, 120°C, 2.5h
78% (2 steps)
H2N
N
O
N
Cu(OAc)2PivOHxylenes
150°C, 24 h
HetAr
35 examples
N
O
N
HetAr
NH
O
O
N1) MeOTf, CH2Cl2rt, 24 h
2) KOtBu, EtOHEt2O rt.
60%
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J. Am. Chem. Soc. 2010, 132, 8270 Angew. Chem., Int. Ed. 2010, 49, 8729. Angew. Chem., Int. Ed. 2013, 52, 10800.
2-‐Pyridyloxy directing group
OPd(OAc)2PhI(OAc)2
Ac2O/AcOH100 °C, 12 h
R
20 examples
N
N OR N
NOAc
OPd(OAc)2
Cu(OTf)2, Ag2O
toluene, 120 °C, 24 h
R
20 examples
N
N OR N
NAr
ArB(OH)2
O1) BBr3, DiPEA
CH2Cl2, 0 °C, 12h
2) Et3N, rt,12hR
20 examples
N
OR NH B
O OHO OH
O MesCO2H, K2CO3
toluene, 120 °C, 20 h
R
23 examples
N
OR N
Ar[RuCl2(p-cymene)]2
F F
ArX
OPd(OAc)2, Ag2CO3
BQ (1 eq), DMSO (4eq)
CH2Cl2, 130°C48h
R
20 examples
N
OR N
ArArBF3K
heated in bomb
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9 JACS. 2000, 122, 12882 JACS. 2001, 123, 10935 JACS. 2012, 134, 12924 OL. 2014, 16, 2748. J. Organometallics 2013, 32, 272
Deprotection of 2-‐Pyridyloxy O
R NBO O
1) Cu(OAc)2, O2, 4Å MSCH2Cl2, 40°C, 15h, 60%
2) MeOTf, PhMe, 100°C, 2h3) Na/MeOH, reflux 30 min 70%
PhNH2
OH
NHPh
1) Pd(PPh3)4, PhMeNa2CO3, reflux 12h 90%
2) MeOTf, PhMe, 100°C, 2h3) Na/MeOH, reflux 30 min92%
OH
ON OMe
R1) MeOTf, PhMe100 °C OH OMe
R
2) Na/MeOH,reflux, 30 min
R = H, 81%R = F, 90%
ON NO2 1) MeOTf, PhMe100 °C 2 h OH NO2
2) Na/MeOH,reflux, 15 min
79%
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JOC. 2009, 74, 7203. J. Organometallics 2010, 29, 4058. OL. 2012, 14, 1154.
C-‐O bond cleavage
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Early work CN
Si2Me6[RhCl(cod)]2 5 mol%
ethylcyclohexane130 °C, 15 h
RSiMe3
R
38 examples
CN
ethylcyclohexane130 °C, 15 h
R R
13 examples
SiEt3
SiEt3Si2Me6
[RhCl(cod)]2 5 mol%
CNSi2Me6
[RhCl(cod)]2 5 mol%
ethylcyclohexane130 °C, 15 h
R
10 examples
XR2 R
XR2
Me3Si
CN
ethylcyclohexane160 °C, 15 h
RH
R
17 examples
HSi(i-Pr)3[RhCl(cod)]2 10 mol%P(O-i-Pr)3 (20 mol%)
CNXantPhos 20 mol%
[RhCl(cod)]2 5 mol%
DABCO 1 eq.toluene 100 °C, 15 h
RB
R
60 examples
OB
OB
O
O
O
O
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12 JACS. 2006, 128, 8152. JACS. 2008, 130, 15982. JACS. 2009, 131, 3174 Bull. Korean Chem. Soc. 2010, 31, 582. JACS. 2012, 134, 115
Title paper
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Optimization of conditions
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Optimization of conditions
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Sequential functionalization
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C-‐OPy cleavage
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CN
(SiMe3)2, PCy3[RhCl(cod)]2 5 mol%
ethylcyclohexane130 °C, 15 h
RSiMe3
R
O
N
O
NtBu
(SiMe3)2[RhCl(cod)]2 5 mol%
(SiMe3)2, IMes[RhCl(cod)]2 5 mol%
toluene, 100°C, 15h
toluene, 130°C, 15h
NR
NR
PhB(OH)2, PCy3[RhCl(cod)]2 5 mol%O
N
O
NtBu
PhB(OH)2, IMes[RhCl(cod)]2 5 mol%
toluene, 100°C, 15h
toluene, 130°C, 15h
NR
NR
B2(pin)2, PCy3[RhCl(cod)]2 5 mol%O
N
O
NtBu
B2(pin)2, IMes[RhCl(cod)]2 5 mol%
toluene, 100°C, 15h
toluene, 130°C, 15h
OH
OH
tBu
92%
90%
ON
B2(pin)2, IMes[RhCl(cod)]2 5 mol%
toluene, 130°C, 15h90%
NR
Deuterium Exchange
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O
NtBu
B2(pin)2, IMes[RhCl(cod)]2 5 mol%
toluene-d8, 130°C, 15h
O
NtBu
B(pin)
tBu
23% D3% D
73%
O
NtBu
B(pin)
tBu
17% D3% D
B2(pin)2, IMes[RhCl(cod)]2 5 mol%
toluene-d8, 130°C, 6h
21% 65%
2% D28% D 90% D
86% D
87% D78% D
O
NtBu
O
NtBu
IMes[RhCl(cod)]2 5 mol%
toluene-d8, 130°C, 15h
87%
10% D19% D 78% D
72% D
74% D78% D
Conclusions • Developed Rh-‐catalyzed boryla%on reac%on for Ar-‐2-‐pyridyl ethers.
• A new applica%on in directed C-‐H ac%va%on that can be used as a handle for further manipula%on.
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OPivR
B2(nep)2,P(4-MeOPh)3[RhCl(cod)]2
toluene130°C, 15 h
BR O
O