Recent Developments in Cross-Couplings: … Developments in Cross-Couplings: Coupling Boronates with...
Transcript of Recent Developments in Cross-Couplings: … Developments in Cross-Couplings: Coupling Boronates with...
Recent Developments in CrossRecent Developments in Cross--Couplings: Couplings: Coupling Coupling BoronatesBoronates with Inert Cwith Inert C--O Bonds, O Bonds,
and and BoronBoronicic AcidsAcids with Carbonylswith Carbonyls
Wen Yuan12-02-09
2
Cross-Coupling Reaction
The reaction of organometallic reagents with organic electrophiles in the presence of metal catalysts
C-C, C-N, C-O, C-S, C-P, etc.
[M]: Group 8–10 Metal catalystsFe, Co, Ni, Cu, Pd, Ru, Rh…
X: I, Br, Cl, OTf …
m: Mg, B, Si, Sn, Zn, Al …
Miyaura, N. Cross-Coupling Reactions: A Practical Guide. Springer: 2002
Study of Transition Metal Catalyst
Total Synthesis of Natural Product
Synthesis of Macromolecule …
3
Importance in Total Synthesis of Haplophytine
Haplophyton Cimicidum
NOHO
ONMe
MeO NOMe
N
HMe
OO
Suzuki-Miyaura couplingHaplophytine
NOBnO
ONCbz
MeO NOMe CO2Me
N
OI
CO2TMSE
TBSO
+
BPin
Pd(dppf)Cl2TlOEt
Isolated by Snyder, 1952
Total synthesis by Nicolaou, 2009
Nicolaou, K. C.; Dalby, S. M.; Li, S.; Suzuki, T.; Chen, D. Y. Angew. Chem. Int. Ed. 2009, 48, 7616.
4
Suzuki-Miyaura Coupling
Miyaura, N. Cross-Coupling Reactions: A Practical Guide. Springer: 2002Matos, K.; Soderquist, J. A. J. Org. Chem. 1998, 63, 461
5
Why Non-Halogen Coupling
22
434
1052
6174
16700
0 5000 10000 15000 20000
R-OH
R-OAc
R-Br
R-OTf
R-I
Org
anic
Ele
ctro
phile
Price $/mol
R:
• Cost
• Commercial availability
• Facile preparation
• Environment friendly
6
[Pd] R-XR-R'
Pd XRPd R'R
B OHOH
OHR'B(OH)3 + X-
path A
R''O-
Pd OR''RR'-B(OH)2(HO)2B
R''O Pd
R'
R path B
path C
1
2
3
45
X=I, Br, Cl, OTf
R-OR''
2
Suzuki-Miyaura Coupling
Miyaura, N. Cross-Coupling Reactions: A Practical Guide. Springer: 2002Matos, K.; Soderquist, J. A. J. Org. Chem. 1998, 63, 461
7
General Outline
AromaticEther
AromaticEster
TautomerizableHeterocycle
From Ketone toTosylhydrazones
8
General Outline
R1CO
R2
AromaticEther
AromaticEster
TautomerizableHeterocycle
From Ketone toTosylhydrazones
9
Oxidative Addition
R-X[M] M
R X
PPh2
PPh2
OCH3RhCl(PPh3)3
P
P
Ph2
Ph2
RhClOCH3
van der Boom, M. E.; Liou, S.-Y.; Ben-David, Y.; Milstein, D. J. Am. Chem. Soc. 1998, 120, 6531.Blanksby, S. J.; Ellison, G. B. Acc. Chem. Res. 2003, 36, 255.
10
Ru Catalyst for Suzuki Coupling
RuPPh3
PPh3
H
H
PPh3
C O
• How does Ru activate C-O bond?
• What is the selectivity between the C-H and C-O bond?
• What is the reasonable mechanism?
• What is the deficiency in this chemistry and how to improve it?
Kakiuchi, F.; Usui, M.; Ueno, S.; Chatani, N.; Murai, S. J. Am. Chem. Soc. 2004, 126, 2706
11
Chelating Assistance for C-O Activation
ORu
OR
Ph3P
PPh3
OC
?
Kakiuchi, F.; Usui, M.; Ueno, S.; Chatani, N.; Murai, S. J. Am. Chem. Soc. 2004, 126, 2706
run ketone product yield
OMe O
OMe
Ph O
Ph
96%1
OOMe
OMe
OPh
OMe
3 75%
2O
Me Ph0%
12
Crystal Structure of Intermediate
ORu
OAr
Ph3P
PPh3
OC
RuH2(CO)(PPh3)3
O
OAr+
toluenereflux, 20h
Ar=p-C6H4CH3
By Discovery Studio ViewerProUeno, S.; Mizushima, E.; Chatani, N.; Kakiuchi, F. J. Am. Chem. Soc. 2006, 128, 16516.
13
Proposed Mechanism
Mechanism :
Kakiuchi, F.; Usui, M.; Ueno, S.; Chatani, N.; Murai, S. J. Am. Chem. Soc. 2004, 126, 2706
14
Selectivity of Activation
C-H activation
C-O activation
Kakiuchi, F.; Kan, S.; Igi, K.; Chatani, N.; Murai, S. J. Am. Chem. Soc. 2003, 125, 1698.
Kakiuchi, F.; Usui, M.; Ueno, S.; Chatani, N.; Murai, S. J. Am. Chem. Soc. 2004, 126, 2706
15
C-O Activation vs C-H Activation
• Bond Dissociation Energy
O
+O
BO
PhRuH2(CO)(PPh3)3
toluene, reflux
O
PhOMe
H H O
OMe
Ph
VS
16
• Bond Dissociation Energy
• Intermediate Observed by NMR
Ueno, S.; Mizushima, E.; Chatani, N.; Kakiuchi, F. J. Am. Chem. Soc. 2006, 128, 16516.
1H NMR 31P NMR
A
B
-5.97
No Ru-H
FAB-MS
35.49; 39.85
33.16
879 (M+-H)
879 (M+-H)
C-O Activation vs C-H Activation
17
C-O Activation vs C-H Activation
• Bond Dissociation Energy
• Intermediate Observed by NMR
Ueno, S.; Mizushima, E.; Chatani, N.; Kakiuchi, F. J. Am. Chem. Soc. 2006, 128, 16516.
1H NMR 31P NMR
A
B
-5.97
No Ru-H
FAB-MS
35.49; 39.85
33.16
879 (M+-H)
879 (M+-H)
Thermodynamic product Kinetic product
18
Scope of Organoboronates
O
+O
BO
PhRuH2(CO)(PPh3)3
toluene, reflux
O
PhOMe
O
CF3
O
NMe2
O O
CH3
O
86% 89% 84% 83% 81%
Kakiuchi, F.; Usui, M.; Ueno, S.; Chatani, N.; Murai, S. J. Am. Chem. Soc. 2004, 126, 2706
19
Deficiency and Improvement1. Ortho Position 2. Price
R=Me 93%
Tobisu, M.; Shimasaki, T.; Chatani, N. Angew. Chem. Int. Ed. 2008, 47, 4866.
0.55
80
334
0 100 200 300 400
Ni
Ru
Pd
Met
al
$/oz
Updated Oct. 2009
Application on Synthesis of Oligoarenes
Symmetric oligoarenes
Asymmetric oligoarenesLittke, A. F.; Dai, C. Y.; Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020.Li, H. Personal communicationGillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2007, 129, 6716.
21
Br
OMe
B(OH)2
cat. [Pd(PPh3)4]Na2CO3
toluene/H2Oreflux, 12h
OMe
77%
BO
O
cat. [Ni(cod)2]/PCy3
toluene, CsF120 oC, 12h 95%
Application on Synthesis of Oligoarenes
Tobisu, M.; Shimasaki, T.; Chatani, N. Angew. Chem. Int. Ed. 2008, 47, 4866.
50g/225$
22
General Outline
R1CO
R2
AromaticEther
TautomerizableHeterocycle
AromaticEster
From Ketone toTosylhydrazones
Starting from Trost-Tsuji Reaction
OAcOAc
PdL
L[Pd] PdL
L
OAc-
(II)
PdL
L(II)
allyl
Nu-
PdL
L(II)
Nureductiveelimination
-PdL2
Nu
Trost, B. M.; VanVranken, D. L. Chem. Rev. 1996, 96, 395. Luo, Y.-R.; Holmes, J. L. J. Phys. Chem. 1994, 98, 303.
Allyl C-O bond is weakerthan Acyl C-O bond
24
Allyl Acetate vs Aryl Acetate
Allyl C-O bond is weakerthan Acyl C-O bond
Luo, Y.-R.; Holmes, J. L. J. Phys. Chem. 1994, 98, 303.Blanksby, S. J.; Ellison, G. B. Acc. Chem. Res. 2003, 36, 255.
25
Acyl C-O Bond Cleavage
NiL2RCOOPh
oxidativeaddition
NiOPh
COR
-COdecarbonylation
L
L
-L
NiOPh
MeOC
L +LNi
OPh
MeL
L
-COdecarbonylation
L2NiOPh
H-C2H4
eliminationL2Ni
OPh
H +CO+L
reductiveelimination
(B)
+CO
disproportionation(A)
L=PPh3
Yamamoto, T.; Ishizu, J.; Kohara, T.; Komiya, S.; Yamamoto, A. J. Am. Chem. Soc. 1980, 102, 3758.
26
Quasdorf, K. W.; Tian, X.; Garg, N. K. J. Am. Chem. Soc. 2008, 130, 14422.
Guan, B. T.; Wang, Y.; Li, B. J.; Yu, D. G.; Shi, Z. J. J. Am. Chem. Soc. 2008, 130, 14468.
Aryl C-O Bond Cleavage
27
Proposed Mechanism for Shi’s work
Guan, B. T.; Wang, Y.; Li, B. J.; Yu, D. G.; Shi, Z. J. J. Am. Chem. Soc. 2008, 130, 14468.
28
Two Pathways for Oxidative Addition
NiL
L
PhOAc
NiL
LOAc
NiL L
OAcNi
L L
OAcNi
L
L
OAc
-L
+LNiL
PhOAc NiL
OAc
NiL
OAcNi
L
O
OC
IN1
IN2
TS1
IN3 IN4
bis-phosphine mechanism
mono-phosphine mechanism
IN5 IN6 IN7
TS2
L=PPh3IN: IntermediateTS: Transition State
Li, Z.; Zhang, S. L.; Fu, Y.; Guo, Q. X.; Liu, L. J. Am. Chem. Soc. 2009, 131, 8815
29
Energy Comparison between Two Pathways
IN1
IN2
TS1
IN3
IN4
30.3
0.0
17.9
5.3
54.9
IN5
IN6
TS2
IN7
10.5
0.8
22.9
-30.3
NiL
L
OAc
NiL
O
OC
NiL
L
NiL L
OAc
NiL
OAc
Oxidative Addition of PhOAc to Ni(0) prefer the monophosphine mechanism
Li, Z.; Zhang, S. L.; Fu, Y.; Guo, Q. X.; Liu, L. J. Am. Chem. Soc. 2009, 131, 8815
Unit: kcal/mol
30
Li, Z.; Zhang, S. L.; Fu, Y.; Guo, Q. X.; Liu, L. J. Am. Chem. Soc. 2009, 131, 8815
NiL
O
OC
IN7
K[PhB(OH)3]Ni
L
O
O BH OH
OH
OK Ni
L OB(OH)2
IN11
H
IN10
KOAc
NiL O
B(OH)2
H
TS4Ni
L OB(OH)2H
IN12
NiL
IN13
B(OH)3
Energy Barrier= 31.2 kcal/mol
Base-assisted Transmetallation:
Transmetallation & Elimination
31
Transmetallation & Elimination
NiL
O
OC
IN7
K[PhB(OH)3]Ni
L
O
O BH OH
OH
OK Ni
L OB(OH)2
IN11
H
IN10
KOAc
NiL O
B(OH)2
H
TS4Ni
L OB(OH)2H
IN12
NiL
IN13
B(OH)3
NiL
IN13
NiL
TS5NiL
NiL
L
+L
IN5IN1
-L
Reductive Elimination:
Energy Barrier= 31.2 kcal/mol
Energy Barrier= 6.0 kcal/mol
Li, Z.; Zhang, S. L.; Fu, Y.; Guo, Q. X.; Liu, L. J. Am. Chem. Soc. 2009, 131, 8815
Base-assisted Transmetallation:
32
Two more Questions Discussed• Why stronger Aryl C-O bond? • Why Ni not Pd in this chemistry?
High reverse barrier is the major reason!
LM
PhX ML
X
MX
L
TS M XL
M=Ni, Pdcomplex
Ph-X Ni(0) barrier Pd(0) barrier
Ph-Br 3.3 3.4
Ph-OAc 26.4 34.0
Ph-NHAc 24.2 31.4
Energy Barrier from η2 complex to TS is the major reason!
Li, Z.; Zhang, S. L.; Fu, Y.; Guo, Q. X.; Liu, L. J. Am. Chem. Soc. 2009, 131, 8815
Unit: kcal/mol
33
One-Pot Reaction
Quasdorf, K. W.; Tian, X.; Garg, N. K. J. Am. Chem. Soc. 2008, 130, 14422.
Me
H
H HHO
O1. PivCl, Et3N, CH2Cl22. (4-MePhBO)3, Ni(PCy3)2Cl2K3PO4, H2O, Dioxane
Me
H
H H
O
62% yieldEstrone
Latest Examples of Ester Coupling
OPiv+ PhZnCl
NiCl2(PCy3)2(5 mol%)
THF/DMA70 oC
Ph
84% yield
Li, B. J.; Xu, L.; Wu, Z. H.; Guan, B. T.; Sun, C. L.; Wang, B. Q.; Shi, Z. J. J. Am. Chem. Soc. 2009, 131, 14656.
Yu, J. Y.; Kuwano, R. Angew. Chem. Int. Ed. 2009, 48, 7217.
Li, B. J.; Li, Y. Z.; Lu, X. Y.; Liu, J.; Guan, B. T.; Shi, Z. J. Angew. Chem. Int. Ed. 2008, 47, 10124.
35
Conclusion for Part 1 and 2
• Chelation assistance helps Ru catalyst to activate inert C-O bond in aromatic ethers
• Cheaper Ni catalyst can activate aryl C-O bond in ether or ester for Suzuki coupling
• Computation studies help propose and understand the mechanism
36
General Outline
AromaticEther
TautomerizableHeterocycle
AromaticEster
From Ketone toTosylhydrazones
38
Synthetic Route for 6-arylpurine Nucleosides
NH
NN
N
O
O
OHOH
HO
NH
NN
N
O
O
OPOP
PO
protection
N
NN
N
X
O
OPOP
PO
N
NN
N
Ar
O
OPOP
PO
activation functionalization
N
NN
N
Ar
O
OHOH
HO
deprotection
traditional multi-step transformation
< 40%
Kang, F. A.; Sui, Z. H.; Murray, W. V. J. Am. Chem. Soc. 2008, 130, 11300.
39
Activation of Carbonyl Group
HN
N
O
N
N POCl3/PhN(Me)2
MeCN/N
N
Cl
N
N
TMSBrButanone
-40 oC
NaIButanone
-40 oC
N
N
Br
N
N N
N
I
N
N
preformation
Reactivity order in transition metal catalyzed couplings:C-I>C-Br,C-OTf,C-OP+>C-Cl
Liu, J.; Robins, M. J. J. Am. Chem. Soc. 2007, 129, 5962.
41
Castro’s Reagent
Han, S. Y.; Kim, Y. A. Tetrahedron 2004, 60, 2447.
Kang, F. A.; Sui, Z. H.; Murray, W. V. J. Am. Chem. Soc. 2008, 130, 11300.
42
N
NN
O P+N
N
N
PF6
PyBOP
N
NN
O Heterocycle
Scope of Phosphonium Salts
EnvironmentalEnvironmentalConsiderationConsideration& Reactivity& Reactivity
Side reactionSide reaction& atom economic& atom economic
Coste, J.; Dufour, M. N.; Pantaloni, A.; Castro, B. Tetrahedron Lett. 1990, 31, 669.
Delarue, S.; Sergheraert, C. Tetrahedron Lett. 1999, 40, 5487.
43
Proposed Catalytic Cycle
Kang, F. A.; Sui, Z. H.; Murray, W. V. J. Am. Chem. Soc. 2008, 130, 11300.
44
Intermediates Verified by NMR
31P NMR spectrumWan, Z. K.; Wacharasindhu, S.; Levins, C. G.; Lin, M.; Tabei, K.; Mansour, T. S. J. Org. Chem. 2007, 72, 10194.
hypoxanthine
45
NH
NN
N
O
O
OHOH
HO
NH
NN
N
O
OHOH
HO
O
NH
NN
N
O
OHOH
HO
NH
NH
NN
N
O
OHOH
HO
S
NH
NN
N
O
OHOH
HO
CH2
PyBroP,ArB(OH)2,PdCl2(PPh3)2, 70-72%
PyBroP, ArOH80-84%
PyBroPArSH,82-88%
PyBroPArNH2,70-75%
Kang, F. A.; Sui, Z. H.; Murray, W. V. Eur. J. Org. Chem. 2009, 461.
Single Step Transformation of C6-modified Nucleosides
46
General Outline
AromaticEther
TautomerizableHeterocycle
AromaticEster
From Ketone toTosylhydrazones
47
Diazo Compound in Pd Coupling Reaction
Ph
NNHTs+
Br
[Pd], Ligand
Base, Solvent70 oC, 4h
Ph98%
Roglans, A.; Moreno-Manas, M. Chem. Rev. 2006, 106, 4622Barluenga, J.; Moriel, P.; Valdes, C.; Aznar, F. Angew. Chem. Int. Ed. 2007, 46, 5587.
48
Bamford-Stevens Reaction
Base
CH3O2SNN
R1
R2
NN
R1
R2
Bamford, W. R.; Stevens, T. S. J. Chem. Soc. 1952, 4735.
49
Metal Free Coupling by Tosylhydrazones
NNHTs
+
B(OH)2
OMe
K2CO3
Dioxane110 oC
OMe
H
93%
Barluenga, J.; Tomas-Gamasa, M.; Aznar, F.; Valdes, C. Nature Chemistry 2009, 1, 494.
Metal free reaction
One-pot reaction
50
Proposed Mechanism
NNHTs
R1 R2 B-
NNTs
R1 R2
N
R1 R2
-Ts-
Ar-B(OH)2
N
N
R1 B
N
R2
OHOH
Ar
R1 R2Ar-B(OH)2
R1
R2 BOH
OHAr
R1
R2 B(OH)2Ar R2
R1
ArH
1 2 3
4
7 8
56
Mechanism
Barluenga, J.; Tomas-Gamasa, M.; Aznar, F.; Valdes, C. Nature Chemistry 2009, 1, 494.
51
Mechanism Studies
Barluenga, J.; Tomas-Gamasa, M.; Aznar, F.; Valdes, C. Nature Chemistry 2009, 1, 494.
Scope of Tosylhydrazones and Boronic Acids
NNHTs
R1 R2
R2
R1
R3
H
110 oCK2CO3
R3-B(OH)2 Dioxane
Barluenga, J.; Tomas-Gamasa, M.; Aznar, F.; Valdes, C. Nature Chemistry 2009, 1, 494.
NNHTs B(OH)2
MeOH
OMe
H
NNHTs B(OH)2
BrO O
Br
Ph
NNHTs
H
B(OH)2
Br Ph
Br
N
H
NNHTsCH3(CH2)5B(OH)2
N
(CH2)5CH3
Hydrazone Boronic acid Product
Ar1
NNHTs
95%
98%
99%
69%
Ar2 B(OH)2 Ar1 Ar2 Ar1 Ar2
1:2
NNHTs Ar B(OH)2 Ar Ar
1:1
53
[1,3]-borotropic Rearrangement
Ar1
NNHTsAr2 B(OH)2 Ar1 Ar2 Ar1 Ar2
+
110 oC
K2CO3
Dioxane+
Ar2B
HO OH
Ar1
Ar2
Ar1
B
HO OH
1 : 2
NNHTs Ar B(OH)2 Ar Ar+
110 oC
K2CO3
Dioxane+
ArB(OH)2
Ar
(HO)2B
1 : 1
Fang, G. Y.; Aggarwal, V. K. Angew. Chem. Int. Ed. 2007, 46, 359.Henriksen, U.; Snyder, J. P.; Halgren, T. A. J. Org. Chem. 1981, 46, 3767.
54
Conclusion
• Ru and Ni can activate the inert C–O bond in ether or ester group for Suzuki Coupling.
• Castro’s Reagent was used for C–C bond formation and application for one–step modification of nucleosides.
• Metal-free reductive coupling directly via Carbonyl group under Suzuki condition