Pd
Bimetallic Catalysis
Rh
－Reactions and Catalysts
Chang Liu
Department of Chemistry
Michigan State University
What’s Bimetallic Catalyst?
1. Alloy of two metals (MxM’Y)
COOH
Ru6Pd6
or Ru10 Pt2
or Ru12 Ag4
COOH
Thomas, J. M.; Johnson, B. F. G.; Raja, R.; Midgley, P. A. Acc. Chem. Res. 2003, 26, 20-30
2. Dinuclear catalysts (one metal complex containing two metal nuclei)
CH3CN
a
H
O O
Pd Pd
N S N
O
CH3CONH2
N
Van den Beuken. E. K.; Feringa, B. L.Tetrahedron 1998, 54, 12985-13011
a:
3. Two-component catalyst (no interaction before reaction)
R
R
PdCl2(PCy)2, Co2(CO)8
CO, H2, NEt3
R
R
CHO
Ishii, Y,; Miyashita, K.; Kamita, K.; Hidai, M. J. Am. Chem. Soc. 1997, 119, 6448-6449
95% yield
N
Classification of Two-component Catalyst
1. Main and co-catalyst
R1
+
R2
R1
+
R2
Cat. a, Cat. b
Cat. a only
Product
100 % yield, 100% ee
Product
50 % yield, 30 % ee
i. co-catalyst activates substrates
R1
+
Activated R1
+
Activated R1
Cat. b
R2
Cat. a
Product
ii. co-catalyst activates main catalysts
Cat. a
+
Cat. b
R1
+
R2
Activated Cat. a
Activated Cat. a
2. Cooperative (same importance)
R1
+
R2
Cat. a only
No reaction
Product
Where We are
Chemistry
Organic Chemistry
Traditional
Other Fields in chemistry
( Inorganic, Analytical, Physical)
Organometallic
Monometallic
Bimetallic
Binuclear
Two-component
Main and co-catalyst
Cooperative
Alloy
Outline
1. Introduction to two-component catalysts
2. Two-component catalysts
(1) Main and co-catalyst
i. Activate the substrates
Pd(0) and Rh(I) catalyzed asymmetric Tsuji-Trost-type reaction
ii. Activate the main catalyst
Pd(0) and Ag(I) catalyzed asymmetric Heck reaction
(2) Cooperative
Pd(0) and Cu(I) catalyzed indole formation reaction
Pd(0) and Cu(I) catalyzed trazole formation reaction
3. The extension of bimetallic catalysts
Æ
Main and co-catalyst
activate the substrates
Pd(0) and Rh(I) Catalyzed Tsuji-Trost Type Reaction
R
Shaw B. L. Chem. Ind. (London), 1961, 517
L
Pd
L
Shaw, B. L. Chem. Ind. (London), 1962,1190
Tsuji- Trost reaction (Trost allylation)
1965 Tsuji’s report
CH2
HC
Pd
CH2
H2C
Cl
CH +
Pd
Cl
H2C
O
HC C OEt
X
X=
O
O
EtOH, DMSO
r.t.
O
C OEt or
CH
X
OEt
O
C OMe
Tsuji, J.; Takashashi, H.; Morikawa,M. Tetrahedron Lett. 1965, 49, 4387-4389
+
C
X
OEt
Main and co-catalyst
Æ
activate the substrates
General Equation and Mechanism of Tsuji-Trost Type
Reaction
[Pd]0, NuH
X
Base
Nu
NuH = malonates, β-diketone, β-keto esters, enamines, β-keto sulfones
X = Br, Cl, OCOOR, SO2R, OCOR, OCONR2, OPO(OR)2 etc.
Nu
Oxidative
Addition
L
Pd
Nucleophilic
Addition
L
X
Nu
Pd(0)Ln
Pd(0)Ln
Catalyst
Association
Pd(0)Ln
X
Starting Material
Dissociation
Nu
Product
C. G. Frost; M. J. Williams Tetrahedron Asym. 1992, 3, 1089-1091
Æ
Main and co-catalyst
activate the substrates
What We Know about Rhodium
Generation of Nucleophile α to cyano group
R2
R1 C C N
H
R2
R1 C C N
H
M
M
R2
R1 C C N
H
New C-C Bond
Formation Reaction
Electrophile
M = Low Valent Metal Ru, Rh, etc.
Murahashi, S.; Mizuho, Y.; Oyasato, N.; Hiraoka, M.; Hirano, M.;Fukuoka, A.. J. Am. Chem. Soc. 1995, 117, 12436-12451
O
O
+
R3
NC
OR4
Me
0.1-1mol%
RhH(CO)(PPh3)
(S, S)-(R, R)-TRAP
Benzene
O
O
R3
Me
OR4
CN
R2P
Me
(R)
H
PR2
H
Me
Fe
Fe
88% ~ 99% yield
R3
4
= Me, Et, Ph, 4-MeOPh, 2-MeOPh, 4-ClPh, H
72% ~ 89% ee
R = Alkyl
Sawamura, M.; Hamashima, H.; Ito, Y. J. Am. Chem. Soc. 1992,114, 8295-8296
(S, S)-(R, R)-TRAP
Æ
Main and co-catalyst
activate the substrates
Rh(I) Catalyzed Nucleophilic Addition
R
0.1-1mol%
RhH(CO)(PPh3)
O
O
+
3
NC
OR4
Me
O
(S, S)-(R, R)-TRAP
R3
Me
Benzene
Ln*Rh
CN
OR4
(R)
Mechanism:
E
O
O
C OR4
O
C OR4
Ln*Rh
N C C
Me
N C C
Me
Catalyst
Rh(I)Ln*
O
E
Me
OR4
CN
Product
O
NC
OR4
Me
Starting Material
Sawamura, M.; Hamashima, H.; Ito, Y. J. Am. Chem. Soc. 1992, 114, 8295-8296
E
Main and co-catalyst
Æ
activate the substrates
Here Comes the Idea
H+ + OH- = H2O
Pd
Can we put them
together?
Nu
E
Rh
Main and co-catalyst
Æ
activate the substrates
New Reaction
O
O
O
+
OR
NC
O
Me
2
1
O
Rh(acac)(CO)2 (1 mol%)
Pd(Cp)(π -C3H5) (1 mol%)
PhTRAP, THF, -40oC, 6h
+ ROH + CO2
O
Me CN
3
b: R= CH(CF3)2
a: R = Et
Mechanism:
P
Pd
P
RO
O C
P
CO2
Pd
P
RO
-
O C
O
O
Rh
N C
Me
P
O
Rh
N C
O
Me
P
OR
NC
P
O C
Rh
P
P
ROH
O
P
O
O
P
OR
P
Pd(0)
O
O
Me CN
Sawamura, M.; Sudoh M.; Ito, Y. J. Am. Chem. Soc. 1996, 118, 3309-3310
O
Me
Main and co-catalyst
Æ
activate the substrates
Closer Look at This Reaction
O
O
O
OR
+
NC
Pd(Cp)(π-C3H5 ) (1 mol%)
PhTRAP, THF, -40oC, 6h
O
Me
2
1
O
Rh(acac)(CO)2 (1 mol%)
+ ROH + CO2
O
Me CN
3
a: R = Et
b: R = CH(CF3)2
1
Pd
Rh
Temp
oC
Time
h
Yield
%
ee
%
1
1a
+
+
0
4
98
32(R)
2
1a
+
-
0
5
97
0
3
1a
-
+
0
24
0
4
1b
+
+
-25
5
91
Entry
Sawamura, M.; Sudoh M.; Ito, Y. J. Am. Chem. Soc. 1996, 118, 3309-3310
93(R)
Æ
Main and co-catalyst
activate the substrates
Lubricant for This Reaction
O
O
O
OR
+
NC
O
Me
2
1
Pd(Cp)(π -C3H5) (1 mol%)
PhTRAP, THF, -40oC, 6h
+ ROH + CO2
O
Me CN
3
b: R= CH(CF3)2
a: R = Et
P
Pd
P
RO
O C
P
Pd
P
RO
O C
-
O
Rh
N C
N C
O
Me
OR
P
NC
P
O C
Pd(0)
ROH
O
Rh
P
P
Me
P
O
P
O
O
P
-
CO2
O
O
Rh(acac)(CO)2 (1 mol%)
Rh
OR
P
O
O
Me CN
Sawamura, M.; Sudoh M.; Ito, Y. J. Am. Chem. Soc. 1996, 118, 3309-3310
O
Me
Æ
Main and co-catalyst
activate the substrates
Possible Ligand Exchange in This Reaction
O
O
O
OR
+
NC
O
Me
Rh(acac)(CO)2 -PhTRAP (1 mol%)
Pd(Cp)(π-C3H5)-dppb (1 mol%)
o
O
O
Me CN
THF, -40 C
93% ee
R = CH(CF3 )2
O
O
O
OR
+
NC
Rh(acac)(CO) 2-dppb (1 mol%)
O
Me
Pd(Cp)(π-C3H5)-PhTRAP (1 mol%)
THF, -40o C
O
O
Me CN
93% ee
R = CH(CF3 )2
Sawamura, M.; Sudoh M.; Ito, Y. J. Am. Chem. Soc. 1996, 118, 3309-3310
Main and co-catalyst
Æ
activate the substrates
Application (extension) of This Reaction
1.
Use the product
O
LiAlH4
O
O
Me CN
MeMgBr
H
96% yield
Me
97% yield
Me CN
O
Me CN
2.
Change different functional groups on the substrates and even different
catalyst
O
X
EWG
R1
Y
R2
O
X
Rh(acac)(CO)2,
[Pd(π -C3H5)(COD)][BF4],
PhTRAP
R1
Y
R2
EWG
Sawamura, M.; Sudoh M.; Ito, Y. J. Am. Chem. Soc. 1996, 118, 3309-3310
R1, R2 = Alkyl
X = C, P
Y = O, N
Main and co-catalyst
Æ
activate the substrates
Application (extension) of This Reaction
2.
Change different functional groups on the reagents and even different
catalyst
O
NC
P OEt
OEt
Me
Rh(acac)(CO)2 (1 mol%)
[Pd(π-C3H5)(COD)][BF4 ] (1 mol%),
O
P OEt
OEt
Me CN
PhTRAP (2 mol%)
1b (2 eq.), THF, -25o C, 72h
5
91% yield
92% ee
(-)-6
R
Rh
cat. Pd(0)
R'OCO
L2Pd
7
8
ReL6N2
Reactions
R
L L
L Re NC
L
N
C
2NCCHRCO2R'
-H2 , -N2
O
R, R' = Alkyl
O
OR'
Pd
Reactions
R
R
OR'
Sawamura, M.; Sudoh M.; Ito, Y. J. Am. Chem. Soc. 1996, 118, 3309-3310
L = PMe2Ph
R, R' = H, Me, Et
Main and co-catalyst
Æ
activate the substrates
Summary of this part
1. Two metals activate their substrates
2. Two known mechanisms
3. Easy to handle and extend
Æ
Main and co-catalyst
activate the main catalyst
Pd(0) and Ag(I) Catalyzed Asymmetric Heck Reaction
•
Heck reaction
I
Pd(OAc) 2 (1 mol%)
+
75% yield
(t-Bu)3N, 100oC, 2h
Heck, R. F.; Nolly. J. P., Jr. J. Org. Chem. 1972, 37, 2320-2322
•
Asymmertric Heck reaction
OTf
Pd(OAc)2 (10 mol%)
(R, R)-DIOP (10 mol%)
n
O
1
n
O
Et3N, Benzene, r.t.
O
2
90% yield
45% ee
Carpenter, N. E.; Kusera, D. J.; Overman, L. E. J. Org. Chem. 1989, 54, 5846-5848
O
H
H
PPh2
PPh2
(R, R)-DIOP
Æ
Main and co-catalyst
activate the main catalyst
Mechanism of Asymmetric Heck Reaction
baseHX
*
P
Reductive
elimination
base
R1 X
4
P
Pd0
Oxidative
addition
3
*
*
P
H
P
9
X
β -hydrogen
*
elimination
R1
1
R
P
PdII
R1
X
5
P
PdII
* α
R5 2 β'
R
R3
β
R4
8
P
R5 *
R2 α
3
βR
R4
7
P
PdII
X
Insertion
R5
α
R2
6
R
β
4
Shibasaki, M.; Boden, C. D. J.; Kojima, A. Tetrahedron 1997, 53, 7371-7395
R3
Æ
Main and co-catalyst
activate the main catalyst
Two Pathways in the Insertion Step
X = OTf
Cationic Pathway
*
P
P
P
PdII
R1
*
R1
X-
P
PdII
R4
R3
11 R2
10
X-
high ee
*
*
R1
Insertion
P
P
PdII
X
R1
5
R5 *
R2 α
R3
*
P
R4
*
R2
P
PdII
R1
X
P
12
P
P
PdII
X
R4 β
7
low ee
P
PdII
R1
X
13
Neutral Pathway
X = Halide and other
Shibasaki, M.; Boden, C. D. J.; Kojima, A. Tetrahedron 1997, 53, 7371-7395
R3
Æ
Main and co-catalyst
activate the main catalyst
How Ag(I) Improve the Regioselectivity
O
Pd(OAc)2 (1 mol%)
PPh3 (12 mol%)
Me
N
Et3N (2 eq.)
CH3CN
I
13
Mechanism:
O
Me
N
O
Me
N
O
+
Regioisomer 14
Regioisomer 15
no Ag
1
:
1
AgNO3
26
:
1
Me
N
O
P
Regioisomer 15
P
Pd0
Me
N
13
16
O
Me
N
O
P
H
H
P
PdII
20
PdII
19
I
I
I
O
P
O
Me
N
P
Me
N
Me
N
H
Regioisomer 14
I
PdII
P
P
18
Abelman, M.M.; Oh, T.; Overman, L.E. J. Org. Chem. 1987, 52, 4130-4133
PdII
P
P
17
I
Æ
Main and co-catalyst
activate the main catalyst
How Ag(I) Improve the Regioselectivity
O
Pd(OAc)2 (1 mol%)
PPh3 (12 mol%)
Me
N
Et3N (2 eq.)
CH3CN
I
13
Mechanism:
O
Me
N
O
Me
N
O
+
Regioisomer 14
Regioisomer 15
no Ag
1
:
1
AgNO3
26
:
1
Me
N
O
P
Regioisomer 15
AgNO3
P
Pd0
Me
N
13
16
O
Me
N
O
P
H
H
P
Pd
II
20
P
Me
N
I
I
PdII
19
I
O
P
O
Me
N
Me
N
II I
Pd
H
P
P
Regioisomer 14
18
Abelman, M.M.; Oh, T.; Overman, L.E. J. Org. Chem. 1987, 52, 4130-4133
PdII
P
P
17
I
Main and co-catalyst
Æ
activate the main catalyst
How Ag(I) Improve the Enantioselectivity
•
First Ag(I) promoted Heck reaction
74% yield
46% ee
Cyclohexene (6 mol%)
Ag2 CO3 (2 eq.)
NMP, 60oC
I
21
•
CO2Me
Pd(OAc)2 (3 mol%)
(R)-BINAP (9 mol%)
CO2Me
H
22
Mechanism:
*
I
P
+
CO2Me
21
23
P
CO2Me
25
P
PdII
P
P
PdII
AgY
*
P
Pd
*
*
P
II
Y-
P
PdII
H
CO2Me
26
Y-
CO2Me
22
+ AgI
I
P
Pd
II
I
*
CO2Me
24
*
P
I
P
P
PdII
low ee
product
CO2Me
CO2Me
28
27
Sato, Y.; Sodeoka, M.; Shibasaki, M. J. Org. Chem. 1989, 54, 4738-4739
Y- = CO32-
Main and co-catalyst
Æ
activate the main catalyst
Which Ag(I) Salt is the Best
CO2Me
I
21
Pd(OAc)2 (3 mol%)
(R)-BINAP (9 mol%)
Cyclohexene (6 mol%)
Ag2 CO3 (2 eq.)
NMP, 60oC
CO2Me
74% yield
46% ee
H
22
Entry
Silver salt
Time
h
Yield
%
ee
%
1
Ag3PO4
188
48
69
2
Ag2SO4
188
11
53
3
AgBF4
252
27
26
4
AgNO3
134
39
27
5
AgClO4
230
33
29
6
AgOTf
208
31
23
7
AgOAc
61
70
6
Sato, Y.; Sodeoka, M.; Shibasaki, M. J. Org. Chem. 1989, 54, 4738-4739
Main and co-catalyst
Æ
activate the main catalyst
Summary of Ag(I) Effect
1. Enhancing the rate of Heck reaction
2. Enhancing the regioselectivity of asymmetric Heck reaction
3. Enhancing the enantioselectivity by introduce the reaction
into the cationic pathway, usually 2 eq. of Ag3PO4, Ag2CO3,
Ag exchanged zeolite can give very high ee in asymmetric
Heck reaction.
4. All those functions are based on the halide scavenger ability
of Ag(I)
Main and co-catalyst
Æ
activate the main catalyst
Problem 1: Where does Ag(I) Scavenge the HX
How Ag enhances the regioselectivity:
O
Me
N
O
P
Regioisomer 15
AgNO3
P
Pd0
Me
N
13
I
16
O
Me
N
O
P
H
H
I
PdII
P
P
P
Me
N
I
I
PdII
19
O
Me
N
Me
N
O
20
PdII
P
P
17
H
I
PdII
P
P
18
Regioisomer 14
How Ag enhances the enantioselectivity:
P
Ag(I)
P
1
R
P
PdII
R
X-
P
P
PdII
R1
X
Neutral Pathway
1
P
PdII
R4
R3
R2
X = OTf
X-
X = Halide and other
Æ
Main and co-catalyst
activate the main catalyst
Conflict in AgNO3
1. We know Ag is to scavenge the halide
O
Pd(OAc)2 (1 mol%)
Me
N
Me
N
O
PPh3 (12 mol%)
Et3N (2 eq.)
CH3CN
I
+
Regioisomer 15
Regioisiomer 14
13
Me
N
O
no Ag
1
:
1
AgNO3 (1 eq.)
26
:
1
70% total yield
Abelman, M.M.; Oh, T.; Overman, L.E. J. Org. Chem. 1987, 52, 4130-4133
2. AgNO3 must be a very good scavenger
O
Pd2(dba)3 (5 mol%)
(R)-BINAP (12 mol%)
Me
N
I
13
O
Me
N
4% yield
AgNO3 (2 eq.)
NMP, 80oC, 26h
0% ee
(S)-32
Ashimori, A.; Bachand, B.; Overman, L. E.; Poon, D. J. J. Am. Chem. Soc. 1998, 120, 6477-6487
Main and co-catalyst
Æ
activate the main catalyst
What Happens without Ag(I) (Neutral Pathway)
O
Me
N
O
Pd2(dba)3 , (R)-BINAP
Me
N
5 eq. of base
I
(R)-32
13
Me
PMP =
N Me
MeMe
Me
N
N
PS =
Entry
Base
Solvent
Pd2(dba)3
%
(R)- BINAP
%
Time
h
Yield
%
ee
%
1
PMP
DMA
10
22
8
71
63
2
PS
DMA
10
22
11
70
46
Ashimori, A.; Bachand, B.; Overman, L. E.; Poon, D. J. J. Am Chem. Soc. 1998, 120, 6477-6487
Main and co-catalyst
Æ
activate the main catalyst
Two Pathways in the Insertion Step
X = OTf
Cationic Pathway
*
P
P
P
PdII
R1
*
X
R1
-
P
PdII
R4
R3
11 R2
10
X-
high ee
*
*
R1
Insertion
P
P
PdII
X
R1
5
R5 *
R2 α
R3
*
P
R4
*
R2
P
R1
PdII
P
P
II
Pd
R1
X
13
X
12
Neutral Pathway
X = Halide and other
P
PdII
X
R4 β
7
P
low ee
R3
Main and co-catalyst
Æ
activate the main catalyst
Can Monodentate Ligands Give High ee?
TBDMSO
OTBDMS
O
5% [Pd2(dba)3] CHCl3,
NMe
I
O
11mol% monophosphane ligands
PMP (4 eq.), MeCONMe2, 100oC
N
Me
39
(S)-Oxindole 40
PPh2
X
X = OTBDMS
27% ee
X = Oi- Pr
23% ee
X = CHPh2
19% ee
X = PPh2 ((R)-BINAP) 66% ee (R)- product
Overman, L. E.; Poon, D. J. Angew. Chem. Int. Ed. Engl. 1997, 36, 518-520
Æ
Main and co-catalyst
activate the main catalyst
What are the Possibilities of Neutral Pathway
P
P
ArX
33
P
P
X
35
X
Pd
P
P
Pd
Ar
X
X
P
P
Ar
Pd
Pd
36
34
P
Ar
P
X-
P
Pd
X
38
X
P
Pd
Ar
X
37
Overman, L. E.; Poon, D. J. Angew. Chem. Int. Ed. Engl. 1997, 36, 518-520
Thorn, D. L.; Hoffmann, R. J. J. Am. Chem. Soc. 1978, 100, 2079-2090
Samsel, E. G.; Norton, J. R. J. Am. Chem. Soc. 1984, 106, 5505-5512
Ar
Main and co-catalyst
Æ
activate the main catalyst
Knowledge Update
P
P
AgY
P
ArX
33
P
Pd
Pd
36
Ar
Cationic Pathway
Y-
high ee
P
P
P
Pd
Ar
P
Pd
X(Y)
42
X
34
high ee
X = Halide
P
P
Pd
Ar
X
37
P
P
Pd
41
Neutral Pathway
Ar
X-
Overman, L. E.; Poon, D. J. Angew. Chem. Int. Ed. Engl. 1997, 36, 518-520
Ar
Main and co-catalyst
Æ
activate the main catalyst
Problem 2: Does Ag(I) Help to Determine Chirality of the
Product?
O
(R)-(BINAP)Pd
Me
N
86% yield
Ag(I) salt
O
70% ee
(S)-32
Me
N
I
13
O
(R)-(BINAP)Pd
Me
N
71% yield
amine
63% ee
(R)-32
Overman, L. E.; Poon, D. J. Angew. Chem. Int. Ed. Engl. 1997, 36, 518-520
Main and co-catalyst
Æ
activate the main catalyst
Another Possibility
(S)-product
AgY
P
ArX
33
X = Halide
P
Ag(I)
P
P
Pd
P
Ar
P
Y-
Pd
P
P
Pd
*
Ar
45
44
Pd
Y
Ar
X
34
base
P
P
Pd
Ar
X
37
Can Ag(I) coordinate to BINAP?
P
P
Pd
P
Ar
P
X-
Pd
X
*
43
41
(R)-product
Overman, L. E.; Poon, D. J. Angew. Chem. Int. Ed. Engl. 1997, 36, 518-520
Ar
Æ
Main and co-catalyst
activate the main catalyst
Can Ag(I) Coordinate to BINAP?
OCH3
Br
O
OCH3
OCH3
Pd2(dba)3 CHCl3 (5 mol%)
(S)-ligands (15 mol%)
O
CaCO3 (2.2 mol eq.)
Ag(I), NMP, 4d
OCH3
46
PPh2
PPh2
O
47
PdL2
OCH3
(S)-BINAP
O
AsPh2
AsPh2
O
OCH3
48
O
(S)-BINAs
Entry
Ag reagent
mol eq.
Ligand
Yield
%
ee
%
1
Ag exchanged zeolite (6.0)
(S)- BINAs
trace
39
2
Ag exchanged zeolite (2.0)
(S)- BINAs
24
52
3
Ag exchanged zeolite (1.0)
(S)- BINAs
21
53
4
Ag exchanged zeolite (6.0)
(S)- BINAP
9
11
5
Ag exchanged zeolite (2.0)
(S)- BINAP
28
47
6
Ag exchanged zeolite (1.0)
(S)- BINAP
39
63
Miuazake, F.; Uotsu, K.; Shibasaki, M. Tetrahedron, 1998, 54,13073-13078
Main and co-catalyst
Æ
activate the main catalyst
Two Tendencies in This Reaction
1. BINAP is better than BINAs
2. 1 eq. is the best
•
Explanation
P
1 eq. AgY
P
ArI
33
P
(same Ag salt, same amount)
(same ligand, same Ag salt)
P
Pd
P
P
P
Pd
Pd
Y
-
Ar
38
Y
36
Pd
P
Ar
+ AgI
Ar
more Ag
I
34
P
Ag(I)
P
49
Pd
Ar
P
Ag(I)
Y-
P
50
+
Pd
Ar
Y-
51
Miuazake, F.; Uotsu, K.; Shibasaki, M. Tetrahedron, 1998, 54,13073-13078
Main and co-catalyst
Æ
activate the main catalyst
Conclusion of Pd(0) and Ag(I) Catalyzed Asymmetric Heck
Reaction
1. For asymmetric Heck reaction, the function of Pd(0) is comparatively clear.
2. Ag(I) is the scavenger of halide, but we don’t know if Ag(I) is doing
something else.
3. Previously, people thought there are two pathways in this reaction, Ag(I)
can direct the reaction into cationic pathway.
4. Two open questions: a: Where does Ag(I) scavenge the halide?
b: Does Ag(I) help to determine the chirality?
Cooperative
Pd(0) and Cu(I) catalyzed Indole Formation Reaction
Transition metal catalyzed indole formation reactions
(1) Pd(II)- alkyne complex
PdII
R
R
Pd(II)
N
R'
NH
R'
NH
R'
R
(2) Intramolecular Heck reaction
X
R
Pd(0)
PdX R
N
R1
N
R1
N
R1
R
(3) Heck type reaction and cyclization
R2
X
+
NH
R1
R3
R2
Pd(0)
R2
R3
PdX
NH
R1
Kamijo, S.; Yamamoto, Y. J. Org. Chem. 2003, 68, 4764-4771
N
R1
R3
Cooperative
Pd(0) and Cu(I) Catalyzed Indole Formation Reaction
R1
OCO2R2
+
1 mol% Pd(PPh3)4
4 mol% CuCl
N
R1
CO2R2
THF
NCO
2
1
3
Entry
R1
R2
Time
h
Yield
%
1
Pr
Me
1
81
2
Ph
Me
2
62
3
p- MeOC6H4
Me
6
62
4
p- CF3C6H4
Me
7
65
5
Pr
i-Pr
1
69
6
Pr
t- Bu
1
72
7
Pr
Ph
1
86
8
Pr
Bn
1
83
Kamijo, S.; Yamamoto, Y. J. Org. Chem. 2003, 68, 4764-4771
Cooperative
Which Catalyst Combination is the Best
Pr
+
NCO
OCO2Me
Pr
5 mol% Pd(PPh3)4
20 mol% 2nd catalyst
THF, 100oC, 1h
Pr
N
CO2 Me
2a
1a
+
N
CO2Me
3a
4a
Entry
2nd catalyst, M
Yield of 3a
%
Yield of 4a
%
1
CuCl
78
0
2
CuBr
70
Trace
3
CuOAc
26
37
4
CuCl (5 mol%)
0
78
5
none
0
89
6
K2CO3
0
87
7
CuCl2
0
0
8
LiCl
0
0
9
ZnCl2
0
0
Kamijo, S.; Yamamoto, Y. J. Org. Chem. 2003, 68, 4764-4771
Cooperative
The Mechanism of This Reaction
OCO2R2
R1
N
C O
R2O
product 3
CO2
Pd
R2O
N
C
2
Pd(0)
R1
Pd OR2
CuCl
5
O
CuCl
8
R1
R2O
N
C
R1
Pd
O
6
CuCl
N
4
N
CO2R2
byproduct 10
CuCl
R2O
N
C
R1
R1
C
O
R1
Pd
O
7
Kamijo, S.; Yamamoto, Y. J. Org. Chem. 2003, 68, 4764-4771
CuCl
1
NCO
Cooperative
Pd(0) and Cu(I) Catalyzed Triazole Formation Reaction
•
The synthesis of triazoles via the [3+2] cycloaddition reaction using
activated substrates
1. Activated alkynes with simple azides
R
+
EWG
EWG
R
R' N3
R'
N
N
N
2. Simple alkynes with activated azides
R
R
R
•
R
+
EWG N3
N
N
N
EWG
What we know about Cu
R
H
Cu
R
Cu
Activated alkyne
Kamijo, S.; Jin, T.; Huo, Z.; Yamamoto, Y. J. Am. Chem. Soc. 2003, 125, 7786-7787
Cooperative
Pd(0) and Cu(I) Catalyzed Triazole Formation Reaction
R
H
+
11
OCO2Me +
12
TMSN3
13
H
R
Pd2(dba)3 CHCl3 (2.5 mol%)
P(OPh)3 (20 mol%)
N
CuCl(PPh3)3 (10 mol%)
AcOEt (0.5 M), 100oC
N
14
Entry
R=
Time
h
Yield
%
1
Ph
10
83
2
p-Cl-C6H4
6
78
3
p-MeO-C6H4
18
63
4
t-Bu
24
58
5
isopropenyl
24
50
6
BnOCH2
6
56
Kamijo, S.; Jin, T.; Huo, Z.; Yamamoto, Y. J. Am. Chem. Soc. 2003, 125, 7786-7787
N
Cooperative
What Catalyst Combination is the Best
Ph
+
H
OCO2Me +
TMSN3
H
Ph
Pd2(dba)3 CHCl3 (2.5 mol%)
dppp (10 mol%)
N
2nd catalyst
(10 mol%)
AcOEt (0.5 M), 100oC
N
N
Entry
2nd catalyst
Time
h
Yield
%
1
none
24
Complex mixture
2
CuCl(PPh3)3
12
73
3
CuCl
12
15
4
CuI
12
12
12
78
5
Ph
Cu
6
CuCl2
12
0
7
Cu power
12
trace
Kamijo, S.; Jin, T.; Huo, Z.; Yamamoto, Y. J. Am. Chem. Soc. 2003, 125, 7786-7787
Cooperative
Mechanism of Pd(0) and Cu(I) Catalyzed Triazole
Formation Reaction
R
H
11
Pd N3
CuClLn
17
HCl
R
CuLn
N
19
CO2
CuLn
R
N
+
TMSOMe
N
16
Pd
18
OCO2Me
Pd(0)
R
H
11
or HCl
H
R
N
N
15
N
14
Kamijo, S.; Jin, T.; Huo, Z.; Yamamoto, Y. J. Am. Chem. Soc. 2003, 125, 7786-7787
12
+
TMSN3
13
Cooperative
Summary of this part
1. T his type of bimetallic catalysis is more complicated.
2. Most of this type are based on Pd.
3. Knowledge about monometallic catalysis can help us to understand
the mechanism.
4. Cooperative bimetallic catalysts have brilliant future.
Summary
Acknowledgement
Dr. Hollingsworth
Dr. Tepe
Dr. Maleczka
My friends:
Group Members:
Yana
feng
xiaoyu
chunrui
zhensheng yu
jun
yiqian
kyoungsoo ying
zhenjie
lingling
meng
tao
lei
zhiyi
ziyang
Li
zhen
hanmi
kun
carol
phalicia
Thank you for your atten
xuezheng
changyou
linjuan
gia
ping
betsy
baseHX
R1 X
4
*
P
base
P
Pd0
3
*
*
P
P
PdII
X
H
9
P
PdII
X
R1
5
P
1
R
R1
P
R5 *
R2 α
P
PdII
X
R4 β
7
X = OTf
Cationic Pathway
high ee
R3
*
P
R1
R1
P
PdII
R1
X
X-
10
*
P
P
PdII
P
P
PdII
R3
6
X-
R2
11
R3
R4
*
R2
12
6
R4
P
PdII
R1
X
13
*
* α
R 2 β'
R
R3
β
R4
8
5
*
P
X = Halide and other
Neutral Pathway
low ee