transition metal catalyzed c h activation on the cmd...
TRANSCRIPT
1
2
3
4
5
Background
Direct Catalytic C‐H Bond Metallation of Arenes
The Catalytic Cross‐Coupling of Unactiviated Arenes
References
Mechanistic Work on the CMD Pathway
Contents
A X M B A BCatalyst
Reaction type 1
Ar Ar'
Ar B(OH)2
Ar' X
Ar ZnX
Ar' X
Ar MgX
Ar' X
Ar SiR3
Ar' X
Ar SnR3
Ar' X
Ar X
Ar X
Negishi Coupling
Stille CouplingSuzuki Coupling
Hiyama Coupling
Kumada Coupling
Ullmann Reaction
Both aromatic compounds must be preactivated
Background
Background
A X H B A BCatalyst
Reaction type 2
A H M B A BCatalyst
Direct Arylation of Unactivated Arenes
EducationPh.D.: University of Toronto, 2002 (Supervisor: Prof. Mark Lautens)
M.Sc.: University of Toronto, 2000 B.Ed.: University of Saskatchewan, 1995
Employment History2007‐2009 Associate Professor with tenure, University of Ottawa
2002‐2007
Assistant Professor, University of Ottawa 1998‐2002 Graduate Student in Organic Chemistry, University of Toronto
1995‐1996 High School Teacher, Ecole Canadienne Française/St. Joseph HS Saskatoon, SK
Keith Fagnou1971‐2009
Background
X
Y
X
R
X = O, CO, NHY = Br, I
10% mol Pd(OAc)2
K2CO3, DMA
R
Ames,
D. E.; Opalko,
A.
Tetrahedron
1984,
40,
1919.Ames,
D. E.; Opalko,
A.
Synthesis
1983,
234.
Direct Catalytic C‐H Bond Metallation of Arenes
Campeau, L.‐C.; Parisien, M.; Leblanc, M.; Fagnou, K.
J. Am. Chem. Soc.
2004,
126, 9186
NO
XN
1) Pd(OAc)2, P(t-Bu)3-HBF4K2CO3, PhMe,110oC
2)Pd/C, HCOONH4MeOH, rt
RR
RR
Direct Catalytic C‐H Bond Metallation of Arenes
Fagnou, K.
J. Am. Chem. Soc.
2005,
127, 18020
Lafrance, M.; Rowley, C.N.; Woo, T. K.; Fagnou, K.
J. Am. Chem. Soc.
2006,
128, 8754
Direct Arylation of Unactivated Arenes Unprecedented Reactivity from a Palladium‐Pivalic Acid Co‐Catalyst SystemPivalic Acid as a Catalytic Proton Shuttle and a Key Element in Catalyst Design
Pd(OAc)2 (3 mol%)Ligand (3 mol%)
t-BuCO2H (30 mol%)
K2CO3 (2.5 equiv.)DMA/C6H6/C6H5OMe(1.2:0.5:0.5), 1200C100% conversion
F
BrA o, m, p-C
o, m, p = 22: 3: 1
A: C = 1: 11
F
Direct Catalytic C‐H Bond Metallation of Arenes
LnPd(0)
PdLn(Ar)Br
ArBr
KBr
OH
O
O
OK2CO3 KHCO3
K
Pd OO
PR3Ar
PdR3PH
O O
PdR3PAr
OOH
PdAr(PR3)
Ar
O
OH
PdR3P
Ar
ArBr + K2CO3
KBr + KHCO3
HPh
Pathway A
Pathway B
Direct Catalytic C‐H Bond Metallation
of Arenes
Lafrance, M.; Fagnou, K.
J. Am. Chem. Soc.
2006,
128, 16496
The Catalytic Cross‐Coupling of Unactiviated
Arenes
Campeau, L.‐C.; Schipper, D.; Fagnou, K.
J. Am. Chem. Soc.
2008,
130, 3266
N
O
H
H
H
N
O
N
O
Ar
Ar
excess
R R' Pd(II) catalyst
N
O
Roxidant(- 2H+)
R
R
R'
1 major
2
3
Stuart, D. R.; Fagnou, K.
Science
2007,
316, 1172
The Catalytic Cross‐Coupling of Unactiviated
Arenes
Entry Indole Arene T (0C) mol % Pd % Conv. 1:2:3
1
2
3
4
5
6
7
8
9
% Yield 1
NAc
NAc
NAc
NAc
NAc
NAc
NAc
NAc
NAc
AcO
H3CCl
Cl
MeO
O
MeO
140 10 100 11.2:1:0.4 84
140 10 100 8110:1:0.6
110*
110*
140
140
140
140
140
10
10
10
20
20
20
20
83
81
100
80
nd
72
nd
6.5:1:0
5.7:1:0
10.5:1:0.3
2.8:1:0
10.4:1:0.4
6.7:1:0
9.9:1:0
63
61
74
54
45
52
42
CH3
H3COMe
MeOF
F
The Catalytic Cross‐Coupling of Unactiviated
Arenes
Stuart, D. R.; Fagnou, K.
Science
2007,
316, 1172
N
H
H
CH3
CH3
H
RN
H
R
CH3
CH3
N
H
R CH3
CH3
Pd(II) cat.
Cu(OAc)2oxidantR = Ac
AgOAcoxidantR = Piv
C-3 oxidativearylation
C-2 oxidativearylation
Stuart, D. R.; Villemure, E; Fagnou, K.
J. Am. Chem. Soc.
2007,
129, 12072
The Catalytic Cross‐Coupling of Unactiviated Arenes
The Catalytic Cross‐Coupling of Unactiviated
Arenes
Stuart, D. R.; Fagnou, K.
Science
2007,
316, 1172
NR
H NRH
R' R'
exess
Pd(TFA)2 (10%)AgOAc
PhH: PivOH1100C
N
OMe
O
CH3
NCH3
O
CH3
N
OMe
O
OMe
N
OMe
O
CH3
N
O
64% 68% 66%
67% 53%
Stuart, D. R.; Villemure, E; Fagnou, K.
J. Am. Chem. Soc.
2007,
129, 12072
The Catalytic Cross‐Coupling of Unactiviated
Arenes
Mechanistic Work on the CMD Pathway
A. D. Ryabov, I. K. Sakodinskaya, A. K. Yatsimirsky. J. Chem. Soc., Dalton Trans. 1985,
2629.
S
N
Hb
Hc O
Ha
S
N
Ha
Hb O
S
NHc
HaHb
N
Hc
Hb
Ha
O
S Ha
Hb
O Ha
HbN
N N
Ha
Hb
N
Ha
Hb
Hc
N
H
CH3 N
H
O
OMe
FF
FF
F
H H
SH 26.5
Hb
SH
F
23.3
22.7
22.5
23.8
30.5
31.1
27.3 23.6
29.7
26.3
25.6
29.9
25.3
28.721.4
30.7
22.5
30.9
27.1
23.2 22.9
22.3 33.9
22.6
1 2 3 4
5 6 7 8
9 10 11 12
13 14
Calculated activation barrier for the CMD pathway.
Mechanistic Work on the CMD Pathway
S
S
F
S
S
F
Ar
ArPd(OAc)2 / PCy3HBF4K2CO3, DMA, 1000C
Ar-Br (0.1 equiv.)PivOH (30 mol%)
Ar = 4-C6H4CO2Et
A
B
A: B = 1:>20
Gorelsky, S.; Lapointe, D.; Fagnou, K.
J. Am. Chem. Soc.
2008,
130, 1084
Mechanistic Work on the CMD Pathway
Gorelsky, S.; Lapointe, D.; Fagnou, K.
J. Am. Chem. Soc.
2008,
130, 1084
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