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何玉萍2012-12-08
Palladium(II)-Catalyzed Alkene Functionalization
hydrogenation
oxidation
hydroformylation
oligomeriaztionpolymerization
RepresentativeReaction
H2C CH2 1/2 O2
Pd/Cu
H3C
O
H
H2C CH2
PdII CH2
CH2PdII
2+
H2O
H+
PdII
OH
+
H
O
CH3
Pd0
2Cu+
2Cu2+H2O
1/2 O2+ 2H+
Smidt, J. Angew. Chem. 1959, 71, 176; Angew. Chem., Int. Ed. 1962, 1, 80.
Wacker Oxidation
Versatility of the PdII-Alkyl Intermediate Arising from Alkene Nucleopalladation
1. Enantioselective Reaction involving Oxypalladation1.1 Phenol Cyclization1.2 Carboxylic acid Nucleophiles1.3 Alcohol Nucleophiles
2. Enantioselective Reaction involving Aminopalladation
3. Enantioselective Reaction involving Carbopalladation
The first example of an enantioselective Pd-catalyzed alkene functionalization
Hosokawa, T.; J. Chem.Soc., Chem. Commun. 1978, 687; J. Chem. Soc., Chem.Commun. 1979, 475.
OHPd(OAc)2 (10%)
pinene (10%)
Cu(OAc)2 (1 equiv)O2 (1atm)
MeOH/H2O
O
12% ee
62% yield
pinene
PdO
O
2
PdOAc
CuX OAc
L
R
OMe
Me
H
Cl
COMe
yield (%)
44
76
77
72
74
ee (%)
26
21
18
6
1
2.1 Phenol Cyclization
Electronic Effect:
Hayashi, T. J. Am. Chem. Soc. 1999, 121, 5063
Tetrasubstituted AlkenesOH
Pd(TFA)2 (10%)
ligand (10%)
BQ (4 eq)MeOH, 60oC
O
N
O
O
N R
R
1: R = i-Pr
96% ee
75% yield
N
O
O
N R
R
COOMe
COOMe2
4% ee
30% yield(with Pd(MeCN)4(BF4)2
N
O O
NR R
3 : R = i-Pr
18% ee
64% yield
N
O O
NR R
4 : R = i-Pr
35% ee
6% yield
R1
R2
R1 = R2 = PPh2 (BINAP)
R1 = PPh2, R2 = OMe (MOP)
R1 = R2 = COOH
R1 = R2 =O
NH
OH
i-Pr
all racemic prouducts
R R R = H, 4-F, 4-Ph, 4-Me, 6-Me
90% - 97% ee
Trisubstituted Alkenes
OH
H
Pd(MeCN)2(BF4)2 (5%)
ligand (10%)
BQ (4 eq), O2 (1 atm)MeOH, 20oC
OH
N
O
O
N R
R
1: R = i-Pr
N
O
O
N R
R
COOMe
COOMe2
Ligand 1: 9% ee, 90% yield
Ligand 2: 88% ee, 90% yield
Hayashi, T. J. Org. Chem. 1999, 64, 1620.
O
NO
N
R'R
R'R
PdII
O
NO
N
R'R
R'R
Pd
PdII
R'
R'
N
ON
O
R
R
not observed
R'
R'
N
ON
O
R
R
Pd
OH
R
Pd(TFA)2 (10%)ligand (10%)
BQ (4 equiv)MeOH
OR
O
NO
N
OMeR'
MeOR'
R' = Ph
R = CH3, 94% ee, 92% yield
N
O
O
N
O
NN
O
R'
R'
R'
R'
R' = Ph
R = CH3, 94% ee, 92% yield
R = H, 93% ee, 79% yield
Zhang, W. B. Tetrahedron Lett. 2007, 48, 4179.J. Org. Chem. 2007, 72, 9208.Tetrahedron Lett. 2007, 48, 4083.Tetrahedron. 2008, 64, 9413.
(-)-sparteine
OH
R
Pd(II) (10%)(-)-sparteine (100%)
3A MS, O2
toluene, 80oC, 36h
O
R
Pd Source
PdCl2
yield(%) ee(%)
2 12
Pd(nbd)Cl2 68 12
53 12
328
20 16
18 51
72 76
83 77
PdBr2
Pd(CH3CN)2Cl2
Pd(CH3CN4)(OTf)2
Pd(OAc)2
Pd(TFA)2
(sp)Pd(TFA)2
nbd
Stoltz, B. M. Angew. Chem., Int. Ed. 2003, 42, 2892; J. Am. Chem. Soc. 2005, 127, 17778.
OH
R
(sp)Pd(TFA)2 (10%)(-)-sparteine (100%)
Ca(OH)2 (2 eqiuv)
3A MS, O2
toluene, 80oC, 36h
O
R
R = OMe: 64% yield, 88% ee
R = C(O)Me: 60% yield, 20% ee
R = t-Bu: 47% yield, 83% ee
R = H: 87% yield, 81% ee
R = Me: 47% yield, 86% ee
[a] Unless noted, reactions were carried out using 0.25 mmol of starting material, 5 mol% Pd(TFA)2
(0.0125 mmol), 20 mol% pyridine(0.05 mmol), 0.5 mmol additive, 125 mg MS3A (500 mg/mmol substrate), and 1 atm O2 in 1.0 mL (entries 1–5) or 2.5 mL (entries 6–7) PhCH3 at 80oC. All yields are based on isolated product. [b] The starting Material was used as a mixture of E and Z alkenes. [c] 10 mol% Pd(TFA)2, 40 mol% pyridine, 2 equiv LiOAc. [d] 3:1 Z:E. [e] 10 mol% Pd(TFA)2, 40 mol% pyridine. [f ] 2 equiv Na2CO3 were added.
Aerobic oxidative heteroatom/alkene cyclizationsEntry Substrate product Time,Yield
O
OHO
O
O
NHTs
O
NHOBn
O
NTs
O
NOBn
O
O
COOEt
COOEt
COOH
O O
OHO
O
8h, 90% yield
8h, 88% yield
4h, 82% yield
48h, 63% yieldc,d
48h, 62% yielde
3h, 87% yieldf
10h, 93% yieldf
1b
2b
3b
4b
5
6b
7 OH
Zhang, W. B. Angew. Chem., Int. Ed. 2012, 51, 9141.
NHPG
OPd(TFA)2 (5%)
ligand (7.5%)
4A MSO2 (balloon)
MeCN, 60oC
NPG
O
N N
O
t-Bu-pyrox
ligand
8 9
R
OH
R2
PdII
oxy-palladation
O PdII
R2
R'
R = H
olefin insertion
O
R2
R'
O
2
R = Me hydride elimination
CO + NuH
R = H
carbonylation
O
2
NuOH
OH
BnO O
OMeO
O
Me
BnO
Pd(TFA)2
ligand (40%)
BQ (4equiv)
CH2Cl2, rt, 3.5d 97% ee
84% yield
N
O
O
NRR
R = Bn
OH
OMe
O OMePd(TFA)2 (3%)ligand (12%)
BQ (4equiv)
MeOH, rt, 15h 96% ee
80% yield
CO (1 atm) O
Tietze, L. F. Angew. Chem., Int. Ed. 2005, 44, 257;Chem.—Eur. J. 2006, 12, 8770; Chem.—Eur. J. 2008, 14, 8956; Heterocycles 2007, 74, 473.
OH Pd(TFA)2 (10%)
ligand (11%)
BQ (4equiv)
(CHCl2)2, 60oC
O
54% ee
55 yield
11% 5-membered ring
N OO N
H HR
RRR
R = i-Pr
ligand
Sasai, H. Tetrahedron: Asymmetry 2010, 21, 767.
Overman, L. E.; Org. Lett. 2007, 9, 911. Adv. Synth. Catal. 2009, 351, 3186.
Nonoxidation Intermolecular Addition of Phenols to (Z)-Allylic Trichloroacetimidates
Addition of Phenols to (E)-Allylic Trichloroacetimidates
Cl3C O
NH n-Pr
ZRHO
3 equiv
1% COP-OAc
CH2Cl2, 38 oC n-Pr
O R
HO
92% ee86% yield
HO
90% ee63% yield
OMe
HO
90% ee97% yield
FHO
91% ee96% yield
HO
90% ee87% yield
Br
ClF
Cl3C O
NH
n-Pr
ERHO
5 equiv
1% catalyst
CDCl3, 38 oCn-Pr
O R
n-Pr
N
O
Cl3C
COP-OAc: 59% (91% ee) 41%
COP-NHCOCl3: 92% (90% ee) 8%
Overman, L. E. J. Am. Chem. Soc. 2005, 127, 2866.
1.2 Addition of Carboxylic Acids to (Z)-Allylic Trichloroacetimidates
Cl3C O
NH
E 3 equiv
1% COP-OAC
CH2Cl2, room temp R
OR
HO
O
R'
O
R'
with R' = Me
Cl3C O
NHOH
97% ee92% yield
Cl3C O
NHOAc
>99% ee90% yield
Cl3C O
NHOTBS
93% ee98% yield
3
with R = n-Pr
HO
O
Me
94% ee88% yield
HO
O
Ph
94% ee98% yield
OMeO
HO
>99% ee92% yield
O
HO
>94% ee60% yield
NO2
Mechanism (Illustrated for Catalysis by (+)-COP-OAc)
*
R2COOH
-H+
NH
OCl3C
R1
Pd
N
C
*
N
OCl3C
R1
Pd
N
C OCOR2
HOAc
Cl3C
O
NH2
R1
OCOR2
PdC
C OAc
*
*
NH
OCl3C
R1
Pd
N
C
-OAc
R1
R2
O
Cl3CNH
O R1
1
3
2
45
6
7
Pd(TFA)2 (15%)
ligand (18%)
BQ (4equiv)
CH2Cl2, rt
N OO N
H HR
RRR
R = i-Pr
ligand
HO OH OMe
HO
70% ee 70% yield
BINAP : no reaction
N
O O
N
R = i-Pr
no reaction
N
O
O
N
R
R
R = i-Pr
no reaction
2.3 Alcohol Nucleophiles2.3.1 Addition of Alcohols to Unactivated Alkene
Sasai, H. J. Am. Chem. Soc. 2001, 123, 2907; Heterocycles 2004, 62, 831.
Pd(TFA)2 (20%)
ligand (24%)
BQ (4equiv)
0oC
N
O
O
N
R
R
R = i-Pr
BzO OH OBnO
95% ee
68% yield
(85 hr)
ON N O
R2
R3R1
O N N O
56% ee
36% yield
ligand
a
b
c
d
R1
H
Me
H
t-Bu
R2
H
Me
i-Pr
i-Pr
R3
H
Me
i-Pr
i-Pr
yield(%)
34
54
59
74
ee(%)
66
87
97
95
OBzHO
OBzHO
PdN
N*
O
O
2HX
OH
OH
PdXX
NN
*
1
*
O OBz
3
HX
O
Pd
OBz
NN* X
O OBz
48O
BnO
2
O
Pd
OBz
NN
*
7
HX
HX
O
Pd
OBz
NN
* X
6
5HX
O
PdN
N*
X
OBz
2
PdN
N
H
X
* PdN
N
H
X
* Pd(0)N
N
Plausible Mechanism of Tandem Cyclization viathe Oxy-palladation
Pd(OAc)2 (5%)
ligand (7.5%)
BQ (50%)AcOH, rt
OH
OH
CO (balloon)O
O O
OH
OH62% ee
29% yield
racemic
N
OO
N
ligand
Yoshida, Z. Tetrahedron Lett. 1985, 26, 4479.
Sasai, H. Org. Lett. 2010, 12, 3480.
Cylization of b - Dicarbonyl nucleophilies
Pd(TFA)2 (10%)
ligand (12%)
BQ (2 equiv)
diglyme, 25oC,12h
N OO N
H HR
RRR
O
O
R
OH
O
R
O
O
R
R = i-Pr
R = 81% ee, 80% yield
R = 51% ee, 60% yield
OR
major minor
Pd(TFA)2 (10%)
ligand (12%)
BQ (2 equiv)
diglyme, 25oC,12h
OH
O R
O
O
R
R =
OR
(z)-1a 72% 12%
Pd(TFA)2 (10%)
ligand (12%)
BQ (2 equiv)
diglyme, 25oC,12h
OH
O
O
O
R =
O
52% 8%
a
b
Plausible Mechanism
PdII
Pd0
O
H
HOR1
R2H
Pd
OHO
R1
R2
O
O H
H
Pd
H
R2
R1
ringflipping
Helimination
O
O H
R2
R1 Helimination
O
O H Pd
H
R2
R1
H
OHO
R1
R2H
Pd H
O
OR1
R2H
Pd
Helimination
O
OH
R2
H
R1
H
O
R2
R1H H
OH
O
R2
R1
O
H
1
2
3
I
II
III
IV
v
VI
H Pd
re-insertion
Hosokawa, T. J. Org. Chem. 2009, 74, 3048.
Intermolecular Alkoxyvinylation of Viny Ethers
OH
OH
N
O
N
O
Bn Bncatechol
ligand
O
O
CuX
PdX
N
N
N
Nbisoxazoline
X = anionic ligands
Ph OHOnBu
Pd(OAc)2 (5%)Cu(OAc)2 (5%)catechol (10%)
ligand (10%)O2, toluene, rt
HOnBu
53% ee
86% yield
O
Ph
PdII
OnBuvia
2.3.2 Addition of Alcohols to ortho-Vinyl Phenols
OH
5% Pd[(-)-Sparteine]Cl2
OH OMe
OMe
OH PdIIX
OMe
PdII X2
MeOH
O
OMe
Pd0
MeOH
quinone methideformation
-HX
oxypalladation
-HX
MeOH
20% CuCl2, O2
rt70% yield
Sigman, M. S. J. Am. Chem. Soc. 2006, 128, 2794. Sigman, M. S. Org. Lett. 2006, 8, 5557.
OH
PdN
N
Cl
Cl
R1
OHR
HR2
R O
PdN
N
Cl
HPd
O
H
NN
Cl-+
H
OPd
N
N
OR2
HO
R2OH
Pd0 A
CuCl2 or O2
Readily OxidizedHidered Alchol
NucleophilicAlcohol
Pd(MeCN)2Cl2 (4%)
ligand (10%)
KHCO3(40%), O2
CuCl (8%)
OH OH Nu'
HO R
Rn Nu'HO
n
RR
toluene, rt
OH O
O
92% ee
57% yield
5:1 dr
OH O
O
OH
90% ee
59% yield
9:1 dr
OH OH
O
96% ee
63% yield
5:1 dr
OH N3
O
84% ee
51% yield
1.4:1 dr
OH
O
94% ee
82% yield
>20:1 dr
N
OH
O
85% ee
53% yield
>20:1 dr
N
OH OMe
O
90% ee
68% yield
10:1 dr
OH OMe
88% ee
50% yield
6:1 dr
O
N
N
O
RR = i-Prligand
Sigman, M. S. J. Am. Chem. Soc. 2009, 131, 17074. Sigman, M. S. J. Am. Chem. Soc. 2010, 132, 7870.
Summary
1.Broad functional-group compatibility air- and moisture-tolerence of PdII catalyst for preparing of important organic building blocks as well asuseful hetero- and carbocyclic molecules.
2. Only a small number of reactions proceed with very high enantiomeric excess, and the successful examples generally have been demonstrated for only a small scope of substrates.
3. Many chiral ligands appear to have deleterious effects on catalyst activity, resulting in the need for high catalyst loadings and long reaction times and a large excess of undesirable oxidants.
4. The discovery of new classes of chiral ligands compatible with the use of molecular oxygen reactivity is in need..