何玉萍 2012-12-08 Palladium(II)-Catalyzed Alkene Functionalization.

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..