Palladium-catalyzed Allylation via Bis-π-allylpalladium Complexes · 2004-03-31 · Outline....

Palladium-catalyzed Allylationvia Bis-π-allylpalladium

Complexes

Xiaoyu XingDepartment of ChemistryMichigan State University

December 17th, 2003

OutlineOutline

. Palladium-catalyzed Allylation via Mono-π-allylpalladiumComplexes (Tsuji-Trost-type Reaction)

. Palladium-catalyzed Allylation via Bis-π-allypalladiumComplexesI. Nucleophilic Addition to Aldehydes and IminesII. Amphiphilic BisallylationIII. ChemoselectivityIV. RegioselectivityV. Enantioselectivity

. Conclusion

Electrophilic Mono-π-allylpalladium Complexes (Tsuji-Trost-type Reaction)

First Tsuji-Trost-type Reaction

CH2

HC

CH2

Pd

Cl

Cl

Pd

H2C

CH

H2C

+ HC CO

OEtX

CHX

O

OEt + C

O

XOEt

X= C OEtO

C MeO

or

EtOH, DMSOr.t.

Tsuji, J.; Takashashi, H.; Morikawa, M. Tetrahedron Lett. 1965, 49, 4387-4388

First Asymmetric Catalytic Tsuji-Trost-type ReactionCO2CH3

OAc

Pd(PPh3)4 (0.75 mol%)(+)-DIOP (10 mol%)

NaCH(SO2Ph)(CO2CH3)

DME, refluxing

CO2CH3

SO2Ph

H3CO2C

CO2CH3

H3CO2C

ee: 24%

+

AcO

H3CO2C

O

OMe

Me PPh2

PPh2

s

s

(+)-DIOP

Trost, B. M.; Strege, P. E. J. Am. Chem. Soc. 1977, 99, 1649-1651


Asymmetric Catalytic Tsuji-Trost-type Reaction

CO2CH3

CO2CH3+

Ph Ph

OAc

THF Ph Ph

CH(CO2CH3)2

Yield: 95%ee: 96%

Pd(OAc)2Ligand

N PPh2

Ligand

Wimmer, P.; Widhalm, M. Tetrahedron Asym. 1995, 6, 657-660

OCO2CH3

+ NaOCCH2CH3

O [Pd(C3H5)Cl]2 Ligand

THAB, CH2Cl2O CH2CH3

O

Yield: 91%ee: 98%

NHNH

PPh2 Ph2P

OO

Ligand THAB= Tetrahexylammonium Bromide

Trost, B. M.; Organ, M. G. J. Am. Chem. Soc. 1994, 116, 10320-10321


General Equation and Catalytic Cycle

Xcat. Pd(0), ligand

NuHBase

Nu

NuH = malonate, primary alcohol, carboxylate, phenol, alkylamine, azide, etc.X = OCOR, OCOOR, OPO(OR)2, Cl, etc.

Pd(0)Ln

X

PdL L

NuX

Catalyst

association

oxidative addition

nucleophilic addition

dissociationPd(0)Ln Pd(0)Ln

Nu

Nu

C. G. Frost; M. J. Williams Tetrahedron Asym. 1992, 3, 1089-1091


Summary

. It is a useful reaction to form new C-C, C-O and C-N bonds

. High enantioselectivities can be realized with a wide range of substrates in a predictable fashion

. Mono-π-allylpalladium complexes are electrophilic, which can be attacked by nucleophiles to afford allylated products

OutlineOutline

. Palladium Catalyzed Allylation via Mono-π-allylpalladiumComplexes (Tsuji-Trost-type Reaction)

. Palladium Catalyzed Allylation via Bis-π-allypalladiumComplexes

I. Nucleophilic Addition to Aldehydes and IminesII. Amphiphilic BisallylationIII. ChemoselectivityIV. RegioselectivityV. Enantioselectivity

. Conclusion

Nucleophilic Addition to Aldehydes and Imines

Different Reactivity between Mono- andBis-π-allylpalladium Complexes

Mono-π-allypalladium Complexes

Bis-π-allylpalladium Complexes

Pd

η3

L-L

PdL

η1

1

2

3

electron sufficient

PdLGL

η3

L-L

PdL

LGL

η1electron deficient

PdL LG

Nu

Nu

Pd

E

E


Discovery of Bis-π-allylpalladium Complexes

Nakamura, H.; Iwama, H.; Yamamoto, Y. J. Am. Chem. Soc. 1996, 118, 6641-6647

SnBu3 +PdCl2(PPh3)2 (10 mol%)

THFPhCHO

Ph

OH

Yield: 64%Mechanistic Study

SnBu3 + PdCl2(PPh)2

PdPPh3

ClPh3P

PdCl

PPh3

+ PPh3

Bu3SnCl +

SnBu3 Bu3SnCl Pd + 2PPh3

PdPPh3

+ PPh3

PhCHOX PhCHO

Ph

OH


Catalytic Cycle

SnBu3 +PdCl2(PPh3)2 (10 mol%)

THFPhCHO

Ph

OH

Yield: 64%

Pd PdPPh3

+ PPh3

PhCHO

Pd

O H

Phnucleophilic addition

Pd OPh

SnBu3

Ph

OSnBu3

Ph

OH

coordination

transmetalation



Methods to Form Bis-π-allylpalladium Intermediates From Pd (II)Double Transmetalation

SnBu3 + PdPdCl2(PPh3)2


Single Transmetalation

PdCl

ClPd + SnBu3 Pd + Bu3SnCl

Nakamura, H.; Nakamura, K.; Yamamoto, Y. J. Am. Chem. Soc. 1998, 120, 4242-4243

Allylsilanes

PdCl

ClPd + SiMe3 Pd + Me3SiCl

TBAF

Hexane-THF

Nakamura,K.; Nakamura, H.; Yamamoto, Y. J. Org. Chem. 1999, 64, 2614-2615


Methods to Form Bis-π-allylpalladium Intermediates From Pd(0)Allylstannanes

Pd(0) + LGoxidative addition Pd

LG

L

SnBu3

transmetalation Pd

LG = Cl, OAc

Nakamura, H.; Shim, J.; Yamamoto, Y. J. Am. Chem. Soc. 1997, 119, 8113-8114

Hexamethylditin

Pd(0)Ln

LGR

PdLG

LR

(SnMe3)2

Me3SnLG

PdSnMe3

LR

SnMe3R

PdLG

LR

+

R

Pd

R

LG = Cl, OAc

R = Ph, CN, COCH3

oxidative addition

transmetalation

reductive elimination

Wallner, O. A.; Szabo, K. J. Org. Lett. 2002, 4, 1563-1566'


Methods to Form Bis-π-allylpalladium Intermediates From Pd(0)Bis(pinacolato)diboron

OAcR O

OB B

O

O+

Pd2(dba)3 (6 mol%)DMSO B

O

O

R

Ph CH

NBs

PhR

NHBs

xPd

OAc

LR

PdLPd L

-L RR

RR

O

OB OAc

+

+R R

Ph CH

NBs

Sebelius, S.; Wallner, O. A.; Szabo, K. J. Org. Lett. 2003, 5, 3065-3068'

Ishiyama, T.; Ahiko, T.; Miyaura, N. Tetrahedron Lett, 1996, 37, 6889-6892


Chemoselective Allylation of Imines in the Presence of Aldehydes

R2CHO+

N

R2

R1

SnBu3 (1 equiv) / BF3.OEt2 R2

OH N

R2

R1

+

SnBu3 (1 equiv)

cat. PdCl2(PPh3)2

R2 H

O

+R2

NHR1

Pd-catalyzed 99 97 : 3

Lewis Acid Promoted 96 <1 : 99

Pd-catalyzed 90 90 : 10

Lewis Acid Promoted 95 10 : 90

imine aldehyde condition yield(%) ratio of amine/alcohol

N

O2N

CO2Me

HCO

NO2

N

MeO

CO2Me

HCO

OMe



Chemoselective Allylation of Imines in the Presence of AldehydesPd-catalyzed

Pd

R2CHO

PdO H

R2

Pd OR3

NR1

R2

PdN R2

HR1

LPd N

R2L

R1

alcoholamine

SnBu3LL

Lewis Acid Promoted

NR2

R1

O

R3 H

BF3BF3

more electrophilicless electrophilic

Lewis acid activates botheletrophiles in the same manner



Summary

. The reactivity of bis-π-allylpalladium complexes is different to that of mono-π-allylpalladium complexes

. Bis-π-allylpalladium complexes can be obtained by different methods

. Nucleophilic addition to imines via bis-π-allylpalladium intermediates is chemoselectively preferred

Amphiphilic Bisallylation

Idea Derived from the Known

Allyl groups in mono-π-allylpalladium complexes are electrophiles

PdX

LNu

Tsuji-Trost-type Reaction

Allyl groups in Bis-π-allylpalladium complexes are nucleophiles


PdE

Is it possible to happen?


Pd

E Nu E Nu


The First Example

Mechanism 2 SnBu3 +

Pd EWG2

EWG1R1

R2

Pd

Pd(0)Cl

PdCl

SnBu3

Bu3SnCl

PdCl2(PPh3)2

EWG1

EWG2

R2R1

R1

R2 EWG2EWG1

EWG2

EWG1R1

R2

+ SnBu3 + X cat. Pd

THF, r.t.

R2R1EWG2

EWG1

EWG1 = CNEWG2 = CN, p-(NO2)C6H4, COOEt, SO2Ph

Nakamura, H.; Shim, J.; Yamamoto, Y. J. Am. Chem. Soc. 1997, 119, 8113-8114


. Intramolecular VersionCl SnBu3

Pd(PPh3)4 Pd Ph CN

CN+

Ph Ph CNCN

PhCNCN

CNCN + +

[4+2] adducts [8+2] adduct1 2 3

1734

19 10 40 18 34 18

THF/r.t.DMF/r.t.

CH2Cl2/reflux

12 3

31 2

[8+2] adduct[4+2] adducts

Yield of products (%)

solvent/tempentry

Nakamura, H.; Aoyagi, K.; Shim, J.; Yamamoto, Y. J. Am. Chem. Soc. 2001, 123, 372-377


. THF and DMF

Nakamura, H.; Aoyagi, K.; Shim, J.; Yamamoto, Y. J. Am. Chem. Soc. 2001, 123, 372-377

. CH2Cl2

PdCN

CN

R

CN

CN

R

Pd3

PdL

CN

CNR

Pd

CNNCR

1 + 2

34753

34 1832 12 4 23

Ph4-MeOC6H44-CF3C6H4

12 3

31 2

[8+2] adduct[4+2] adducts

Yield of products (%)

Rentry


.Tandem Reaction of Alkynylaldehydes

SnBu3

OHC

Ph

Cl+ +[PdCl(C3H5)]2

THF, r.t.

O O PhPh

+5-exo-dig 6-endo-dig

1

2 386% 10%

MechanismSnBu3

Cl

Pd(0) PdCl

LnPd

1

Pd+

Ph

-O

Ph-O

Pd+

ab

2 + 3

Nakamura, H.; Ohtaka, M.; Yamamoto, Y. Tetrahedron Lett. 2002, 43, 7631-7633


Summary

. Bis-π-allylpalladium complexes act as the amphiphlic catalytic allylating agent

. Besides activated olefins, other substrates, such as isocyanates, carbon dioxide, benzynes, aldehydes and imines, can also generate double allylated products

OutlineOutline

. Palladium-catalyzed Allylation via Mono-π-allylpalladium Complexes (Tsuji-Trost-type Reaction)

. Palladium-catalyzed Allylation via Bis-π-allypalladium ComplexesI. Nucleophilic Addition to Aldehydes and IminesII. Amphiphilic BisallylationIII. ChemoselectivityIV. RegioselectivityV. Enantioselectivity

. Conclusion

Chemoselectivity

Chemoselectivity

SnBu3

+

Pd2dba3.CHCl3 (5 mol%)

DMF, 50oC

O Yield: 88%

Cl

CHO

Pd2dba3.CHCl3 (5 mol%)THF, r.t.


THF, r.t.PPh3 (40 mol%)

ClOH

Yield: 88%

CHO

Yield: 70%


Nucleophilic Addition

Allyl-allyl Reductive Coupling

Bao, M.; Nakamura, H.; Inoue, A.; Yamamoto, Y. Chem. Lett. 2002, 123, 158-159Nakamura, H.; Bao, M.; Yamamoto, Y. Angew. Chem. Int. Ed. 2001, 40, 3208-3210

Chemoselectivity

Allyl-allyl reductive Coupling vs. Nucleophilic Addition

Nakamura, H.; Bao, M.; Yamamoto, Y. Angew. Chem. Int. Ed. 2001, 40, 3208-3210

Ph

OH

Yield: 96%

Pd2(dba)3.CHCl3 (5 mol%)THF, r.t., 11h

ClPh SnBu3+ +Ph

O

H

ClPh SnBu3+ +Ph

O

H

Ph

+

Ph

Yield: 90%

Pd2(dba)3.CHCl3 (5 mol%)THF, r.t., 19h

PPh3 (40 mol%)

Chemoselectivity

Mechanism:ClPh

SnBu3

+ Pd(0) Pd Cl

Ph

Bu3SnCl

Pd

Ph

PPh3

PdPh3P Pd

Ph

PPh3

Ph

PdPPh3

Ph3P

Ph

Ph

Ph

O

H

Ph

OH

Pd

PhPh

OH

Pd

Ph

O

Ph

SnBu3

Ph

OSnBu3H+

Nakamura, H.; Bao, M.; Yamamoto, Y. Angew. Chem. Int. Ed. 2001, 40, 3208-3210

Chemoselectivity

Chemoselectivity

SnBu3

+


DMF, 50oC

O Yield: 88%

Cl

CHO

Pd2dba3.CHCl3 (5 mol%)THF, r.t.


THF, r.t.PPh3 (40 mol%)

ClOH

Yield: 88%

CHO

Yield: 70%



Allyl-allyl Reductive Coupling

Bao, M.; Nakamura, H.; Inoue, A.; Yamamoto, Y. Chem. Lett. 2002, 123, 158-159Nakamura, H.; Bao, M.; Yamamoto, Y. Angew. Chem. Int. Ed. 2001, 40, 3208-3210

Chemoselectivity

Nucleophilic Addition vs. Amphiphilic Bisallylation. Solvent Effect:

SnBu3Pd(0)

Cl

CHO

PdIICl

Bu3SnCl

O

H

PdII

O

H

PdII

O

PdII

O

PdII

O-

+

O

preferred in DMF

Bao, M.; Nakamura, H.; Inoue, A.; Yamamoto, Y. Chem. Lett. 2002, 123, 158-159

Chemoselectivity

Nucleophilic Addition vs. Amphiphilic Bisallylation. Ligands Effect:

Cl+Ts-NCO + (SnMe3)2

[Pd(C3H5)Cl]2 (5 mol%)

THF, 60oC, 24hPPh3 (5 mol%)

59%

[Pd(C3H5)Cl]2 (5 mol%)

THF, 60oCwithout PPh3

N

O

no double allylated product

Ts

NPd

O

Ts

SolventPPh3

NPd

O

Ts

Ph3P

Wallner, O. A.; Szabo, K. J. J. Org. Chem. 2003, 68, 2934-2943‘

Chemoselectivity

Summary

. Three different pathways are possible for the bis-π-allylpalladiumintermediates.

. The allyl-allyl reductive coupling can be avoided by the employment of low phosphine concentration or phosphine free conditions .

. Polar solvents and a certain amount of phosphine ligand prefer bisallylation to nucleophilic addition.

Regioselectivity

Regioselectivity

Pd

EWG

EWG

R

R'C

R''Z

R

EWG EWG

ZH

R''R'

Z= O or NR

Pd

EWG

EWG

R

R'C

R''Z

Z= O or NR

R3R1

R6R4

R2

R5

multiple products

multiple products

Regioselectivity

Regioselectivity

SnBu3

+

Cl

cat. Pd

CO2

cat. Pd

Ph

CN

CN

cat. Pd

R1

R2R1

R2R1

R2

O O

O O

O O

O O

Ph Ph

PhPh

+

+

+

+

+

NC CN

NC CN NC CN

NC CN

Solin, N.; Narayan, S.; Szabo, K. J. J. Org. Chem. 2001, 66, 1686-1693‘

Regioselectivity

Regioselectivity

SnBu3

R1

+ Cl

R2

CNPh

CN

Pd(PPh3)4 (5 mol%) R2

R1 Ph

NC CN

Pd

PPh3

PdPPh3

PdPh3P

E = -3.0 kcal/mol E = 0.0 kcal/mol

+78

69

70Bn

Me

n-Pr

Me

Me

Me

4

5

6

6565

8484

8888

yield (%)

Me Me

nn--PrPr

BnBn

R2

HH

HH

HH

R1

1 1

22

33

entry

Solin, N.; Narayan, S.; Szabo, K. J. J. Org. Chem. 2001, 66, 1686-1693‘

Regioselectivity

RegioselectivityOther substituent patterns

Wallner, O. A.; Szabo, K. J. Org. Lett. 2002, 4, 1563-1566'

+

Pd

R2

R1

R2

Pd

R2

PPh3R1

R2

PPh3

PdPh3P

R2

R1

+

R2

E NuE

Nu R2R1

R2

Pd

R2R2

PPh3R1

Pd

R

PPh3

Pd

R

PPh3

PdPh3P

RR

R

R

E NuE

Nu RR

+

Regioselectivity

Summary

. Different substituent patterns on two allyl moieties lead to a mixture of isomeric products.

. Good regioselectivity could be obtained by choosing propersubstituent patterns

. The steric differences decide the reactivity of the two allyl moieties

. The electrophilic attack occurs at the more substituted terminal carbon of nucleophilic allyl moiety

Enantioselectivity

Enantioselectivity. Nucleophilic Addition

074DMFPh Ph5

81

80

80

82

ee(%)

62

72

62

66

yield (%)

DMF

THF

DMF

THF

solvent

Ph Bn

Ph Bn

Ph p-MeOC6H4CH2

Ph p-MeOC6H4CH2

imineR1 R2

1

2

3

4

entry

PdCl

ClPd + SnBu3

Pd + Bu3SnCl

R1

NR2

solvent, 0oC

R1

HNR2

PdN


Enantioselectivity

Probable Transition-State Models

NPd

H

>>Pd

N

H

R

HN

R

HNBn BnR S

1

23

4567

8 9

10

1

23

4567

8 9

10


Enantioselectivity

38 2

77 7

imine Product yield (%) ee (%)

N NH

N NH

NPd

H

R

PdN R'

R

H

R

HN

R

HNBn BnR S

1

23

4567

8 9

10

1

23

4567

8 9

10

R'

Fernandes, R. A.; Stimac, A.; Yamamoto, Y.; J. Am. Chem. Soc. 2003, 123, 14133-14139

Enantioselectivity

Summary

. High ee value could be obtained by using one chiral allyl moiety in nucleophilic addition

. No good enantioselectivity has been reported about amphiphilic bisallylation till now

. It is a challenge to get high ee value in amphiphilic bisallylation

ConclusionConclusion

Palladium-catalyzed Allylation

Mono-allylpalladium Complexes Bis-allylpalladium Complexes

Nucleophilic Attack Allyl-Allyl Coupling



AcknowledgementAcknowledgementDr. Hollingsworth Dr. Tepe

Group Members: Li

XuezhengZhen

ChangyouHanmiLinjuan

Kun Ping Gia

CarolFelicia Betsy

Thank

You

for

Your

Attention

My friends: FengYu

Chang Chunrui

TaoJun

ZhenjieLingling

MengLei

Zhiyuan

Palladium-catalyzed Allylation via Bis-π-allylpalladium Complexes · 2004-03-31 · Outline....

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