development of palladium-catalyzed c-n bond formation reaction wu hua 2010.4.24
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Development of Palladium-Catalyzed C-N Bond Formation Reaction
Wu Hua
2010.4.24
First Intermolecular Carbon-NitrogenBond Formation
Br Bu3SnNR2+[(o-MeC6H4)3P)2PdX2
NR2 + Bu3SnBr
R R
In 1983 Kosugi et al. published report of intermolecular carbon-nitrogen bond formation. Only electron neutral aryl bromides gave products in good yields. Vinyl Bromides and aryl bromides containing electron donating or electron withdrawing groups gave products in low yields.
Only Unhindered dialkyl amides gave good yields of amination products.
M. Kosugi, M. Kameyama, T. Migita, Chem. Lett. 1983, 927
First Intramolecular Carbon-NitrogenBond formation
NOEt
O
EtO
O
H2N
Br
NOEt
O
EtO
O
HN
Pd(PPh3)4
First example of palladium(0) mediated carbon-nitrogen bond formation using stoichiometric quantities of palladium(0) was reported by Boger in 1984
eq. Pd(PPh3)4 Solvent Temperature/oC Time/h Yield/%
1.0 THF(sealed tube) 80 20 50
1.2 THF(sealed tube) 80 21 81
1.5 THF(sealed tube) 80 21 84
1.2 Dioxane 100 20 50
1.5 Dioxane 100 24 73-80
1.2 Toluene 100 24 43
0.01 THF(sealed tube) 80 24 0
D. L. Boger, J. S. Panek, Tetrahedron Lett. 1984, 3175
Catalytic examples using amino stanannes
Bu3Sn-NEt2 + HNRR' ~80oC-HNEt2
Bu3Sn-NRR'
Br
R''
1-2.5 mol% Pd cat.Toluene, 105oC
NRR'
R''
Work reported by S. Buchwald:
Examples:
EtO2C N
Ph
Me2N N
Ph
NN
H
88 % 81 %
66 % 55 %
A. S. Guram, S. L. Buchwald, J. Am. Chem. Soc. 1994, 7901.
Catalytic examples using amino stanannes
L-Pd ArBrArNR2
PdAr L
Br BrPd
L ArBr
Pd-LAr
PdNR2
ArL
n=1,2
L2Pd
R2NSnBu3BrSnBu3
L(NHR2)PdX2
L2PdX2
R=Me,Etreduction/dissoc.
Work reported by J. Hartwig:
R Br Bu3SnNMe2+[(o-MeC6H4)3P)2PdX2
R NMe275-85%
Catalytic cycle:
F. Paul, J. Patt, J. F. Hartwig, J. Am. Chem. Soc. 1998, 5969.
A lot of advantages !
Achieving the Same Chemistry Withoutthe use of Tin Reagents
ArBr + HNRR'L2Pd or L2PdCl2
LiN(SiMe3)2
L=P(o-tol)3
ArNRR'
Work reported by J. Hartwig:
L-Pd ArBrArNR2
PdAr L
Br BrPd
L ArBr
Pd-LAr
L2PdL2PdCl2reduction
HNR2Pd
L Br
Ar NR2
H
PdL
Ar NR2
LiN(TMS)2
HN(TMS) 2 + LiBr
Catalytic cycle:
J. Louie, J. F. Hartwig, Tetrahedron Lett. 1995, 3609.
Achieving the Same Chemistry Withoutthe use of Tin Reagents
R
I + HNRR'
cat. Pd2(dba)3P(o-tolyl)3NaOtBuDioxane
65oC or 100oCR
NRR'
HN HN
O
O
HNBu2 HN
n-Hexyl-NH2H2N NH2
Work reported by S. Buchwald:
Tested a variety of aryl iodides with primary and secondary amines:
I MeO I Cl I
I
NBu2
O
MeO
I
I
Good yields for all, 59-79%.
J. P. Wolfe, S. L. Buchwald, J. Org. Chem. 1996, 1133.
Catalyst Development
PPh2
Ph2P
Br
+ RNH2
Pd2(dba)3BINAP
NaOtBu
Toluene
80oC
NHR
Buchwald found dramatic improvements in yield and substrate generality by using BINAP as the ligand
Catalyst loadings are also significantly reduced
Compared with 35% when using P(o-tolyl)3 and R = n-hexyl
R Mol% Pd Reaction time/h Yield/%
n-hexyl 0.5 2 88
Bn 0.5 4 79
Bn 0.05 7 79
Cyclohexyl 0.5 18 83
J. P. Wolfe, S. Wagaw, S. L. Buchwald, J. Am. Chem. Soc. 1996, 7215.
BINAP Reaction Mechanism
ArBrArNRR'
(BINAP)Pd(dba)
NaOtBu
NaBr + HOtBu
(BINAP)Pd
Pd2(dba)3 + BINAP
(BINAP)Pd(Ar)(Br)
(BINAP)Pd(Ar)(Br)
NHRR'
(BINAP)Pd(Ar)[NRR']
Catalyst developmentHartwig developed a dppf based system that shows enhanced catalytic qualities
Fe
PPh2
PPh2
PdCl2
Good for primary amines and works on electron deficient aryl halides
R
X + H2NR + NaOtBu
5mol% (DPPF)PdCl2DPPFTHF
100oC/~3h
R
NHR
M. S. Driver, J. F. Hartwig, J. Am. Chem. Soc. 1996, 1133.
Coupling of Secondary Acyclic Amines
t-Bu
Br
Bu2NH+
0.25 mol% Pd2(dba)3
0.75 mol% Ligand
1.4 equiv. NaOtBu
toluene
80oC t-Bu
NBu
Bu
Fe
PPh2
PPh2
NMe2
Fe
PPh2
Fe
PPh2
NMe2
Fe
PPh2
OMe
(rac)-BPPFA FcPPh2 (rac)-PPFA (rac)-PPF-OMe
Ligand Time/h Isolated yield/%
P(o-tolyl)3 48 77
BINAP 48 -
DPPF 48 -
(rac)-BPPFA 48 -
FcPPh2 48 -
(rac)-PPFA 24 89
(rac)-PPF-OMe 5 93
J. Marcoux, S. Wagaw, S. L. Buchwald, J. Org. Chem. 1997, 1568.
Coupling of Aryl Triflates
R
OTf + HNRR'
2 mol% Pd(OAc)2
BINAP or Tol-BINAP
NaOtBu
Toluene
80oC R
NRR'
Buchwald:
R
OTf + HNRR'
1-5 mol% Pd(OAc)2
3-10 mol% BINAP or DPPF
1.5 equiv. NaOtBu
Toluene
85oC R
NRR'
Hartwig:
Both systems use electron rich and electron poor aryl triflates with primary and secondary amines (cyclic and acyclic)
J. P. Wolfe, S. L. Buchwald, J. Org. Chem. 1997, 1264.
J. Louie, M. S. Driver, B. C. Hamann, J. F. Hartwig J. Org. Chem. 1997, 1268.
Intermolecular Markovnikov Hydroamination of vinylarenes with alkylamines
HNRR' + R
5 mol% Pd(O2CCF3)2
10 mol% DPPF
20 mol% CF3SO3H
Dioxane, 120 oC, 24 hR
NRR'
(DPPF)Pd
OTf
HNRR'Via:
Amines: OHN NRHN HN
n = 1,2
HN
Me
BnHN
Me
n-hexyl
Products formed in 43-79 % yield
M. Utsunomiya, J. F. Hartwig, J. Am. Chem. Soc. 2003, 14286.
Synthesis of Enamines and Imines
R1 BrR2 N
H
R3 R1 NR3
R2Pd2(dba)3/BINAP
NaOtBu
Toluene+
Pd(OAc)2/BINAP or
Examples:
N
O
96 %
N
96 %
N
N
O
95 %
Bn
N
O
86 %
BnO
N
O
96 %
C7H15
N
O
96 %
75 %
M. Fernández, F. Aznar, C. Valdés, J. Barluenga, Chem. Eur. J. 2004, 494.
Scope and Limitations of the Pd/BINAP-Catalyzed Amination of Aryl Bromides
John P. Wolfe, Stephen L. Buchwald. J. Org. Chem. 2000, 65, 1144-1157
Catalytic Amination of Aryl Bromides Using NaO-t-Bu as the Base.
Note: When the weak base Cs2CO3 is employed, a much wider variety of functional groups are tolerated.
Tanoury, G. J. Senanayake. Tetrahedron Lett. 1998, 39, 6845
ClCl
O
ON
N N O N NH
Br NN
N
O
OTBS
Pd2(dba)3, BINAP
NaOBu-t, 81%
ClCl
O
ON
N N O N N NN
N
O
OTBS
Application In The Synthesis
N
NCl
F
NHH2N
Pd2(dba)3
BINAP
NaOBu-t+ N
N
F
NHNH
Selectivity 35:1
Yield: 85%
Hong. Y. Tetrahedron Lett. 1998, 39, 3121
Selective Cross-Coupling Using BINAP
Stephen L. Buchwald. J. Am. Chem. Soc. 2003, 125, 6653-6655
Jacqueline E. Milne, Stephen L. Buchwald. J. Am. Chem. Soc. 2004, 126, 13028-13032
Eric R. Strieter, Stephen L. Buchwald. Angew. Chem. Int. Ed. 2006, 45, 925 –928
Catalyst Activation Mechanism
Stephen L. Buchwald. J. Am. Chem. Soc. 2007, 129, 13001-13007
X
R H2N R'
O
+
Pd2dba3, Ligand
K3PO4, t-BuOH
HN
RO
R'
A New Class of Air- and Moisture- stable Pd Precatalysts
They are particularly useful in cases where a highly active Pd complex is required to promote a difficult cross-coupling reaction or where functional group instability requires the use of low temperatures.
Mark R. Biscoe, Brett P. Fors, Stephen L. Buchwald. J. Am. Chem. Soc. 2008, 130, 6686–6687
Chemoselective Cross-coupling Reactions
Debabrata Maiti and Stephen L. Buchwald. J. Am. Chem. Soc. 2009, 131, 17423–17429
Stephen L. Buchwald. J. Am. Chem. Soc. 2009, 131, 16720–16734
Kelvin Billingsley , Stephen L. Buchwald. J. Am. Chem. Soc. 2007, 129, 3358 3366
Application In Suzuki-Miyaura Reaction
Reduce the loading of catalyst !
Brett P. Fors, Stephen L. Buchwald. J. Am. Chem. Soc. 2009, 131, 12898–12899
N
O
O
O
O
OO
TDA
First, the dative ancillary ligands can be displaced by ammonia to form a catalytically unreactive complex.
Second, reductive elimination from an Ar-Pd-NH2 complex has never been observed, perhaps because complexes of the parent amido group often adopt stable bridging structures.
Third, if reductive elimination did form the arylamine, this product would likely be more reactive than ammonia and would further react to form the diarylamine.
Cross-coupling Reaction With Ammonia
Difficulties Suffered:
Qilong Shen and John F. Hartwig. J. Am. Chem. Soc. 2006, 128, 10028-10029
(i) many kinds of transition metals are deactivated by ammonia to give stable aminecomplexes and
(ii) when a reaction forms a primary amine, this product is more reactive than ammonia and causes problematic overreactions.
It is noteworthy that the use of aqueous ammonia is essential and that ammonia gas did not react at all !.
Takashi Nagano and Shu Kobayashi. J. Am. Chem. Soc. 2009, 131, 4200–4201
Palladium-Catalyzed Asymmetric Dearomatization of Naphthalene Derivatives
Stephen L. Buchwald. J. Am. Chem. Soc. 2009, 131, 6676–6677
Conclusion
First-generation catalyst: Pd/P(o-tolyl)3
Second-generation catalyst: Pd/aromatic phosphines
PPh2
Ph2P
Fe
PPh2
PPh2
PdCl2
Third-generation catalyst: Pd/Hindered alkylphosphines
BINAP DPPF
i-Pri-Pr
PCy2
1. One kind of the Buchwald-Hartwig cross-coupling reaction substrates must be aryl halides and aliphatic halides have not been reported.
2. It will be paid more attention to its use in asymmetric synthesis.