Nickel’Catalyzed’Cross1Coupling’...

Nickel Catalyzed Cross-‐Coupling Reac7ons

Topic Review

Julien

December, 13th 2012

Introduc7on

Cl NiCl2(dppe)

Et2Oreflux, 20 h

Et MgBr

Tamao, K.; Sumitani, K.; Kumada, M. J. Am. Chem. Soc. 1972, 94, 4374

Introduc7on

•  Kumada reac7on (1972)1:

M = MgX and Pd or Ni catalysis •  Sonogashira reac7on (1973):

M = [Cu] and R = alkynyl, Pd catalysis, base •  Negeshi reac7on (1977):

M = ZnX, Pd catalysis •  S7lle reac7on(1977):

M = SnX3, Pd catalysis •  Suzuki reac7on (1979):

M = BY2, Pd catalysis, base

R'-X R' RR MCatalist

Introduc7on

•  Cross-‐coupling : Nobel Price 2010

Introduc7on

Rudolph, A.; Lautens, M. Angew. Chem. Int. Ed. 2009, 48, 2656

Suzuki Cross-‐Coupling

Lou, S.; Fu, G. C. Org. Syn. 2010, 87, 299

n-BuO

BHO

70 °C

n-Bu

BCat

Pd(PPh3)4 (1 mol%)NaOEt

Benzenereflux, 2 h

Br

Ph

n-Bu Ph80%

Miyaura, N.; Yamada, K.; Suzuki, A. Tetrahedron Le:. 1972, 36, 3437

9-BBNn-Dodec Br

n-Dodec

Pd(OAc)2 (4 mol%)PCy3 (8 mol%)

K3PO4•H2O (1.2 equiv.)

THFr.t, 24h


R1 R2

Cl9-BBN R3

6% NiBr2•dyglyme8% 1

KOt-Bu (1.2 equiv)i-BuOH (2.0 equiv)4 Å molec. sieves

i-Pr2O

R1 R2

R3

1.8 equiv. MeHN

PhPh

NHMe1

PhCbzN

PhO

Ph

OTIPSPh

CO2MePh

O O81%

74%64%

70% 71%80%

Lu, Z.; Fu, G. C. Angew. Chem. Int. Ed. 2010, 49, 6676


R2

Br9-BBN R3


KOt-Bu (1.4 equiv)n-Hexanol (1.8 equiv)

4 Å molec. sievesi-Pr2O

R22.0 equiv. MeHN NHMe

1

O O

R3

racemicO

NPh

BnO

NPh

Bn

O

80%94% ee

O

NPh

Bn O54%

98% ee

O

NPh

Bn

O66%

96% ee

O

NPh

Bn OO

Owston, N. A.; Fu, G. C. J. Am. Chem. Soc. 2010, 132, 11908.


R2

Cl9-BBN R3


KOt-Bu (1.2 equiv)i-BuOH (2.0 equiv)4 Å molec. sieves

i-Pr2O

R21.8 equiv.

MeHN NHMe1

NAr

R1

N Ar

R1R3

racemic

CF3

CF3

N

84%88% ee

PhN

82%72% ee

PhOMe

N

92%57% ee

n-BuN

94%86% ee

n-Bu

OOOMe

F

Lu, Z.; Wilsily, A.; Fu, G. C. J. Am. Chem. Soc. 2011, 133, 8154.


Lu, Z.; Wilsily, A.; Fu, G. C. J. Am. Chem. Soc. 2011, 133, 8154.


Li, Z.; Jiang, Y.-‐Y.; Fu, Y. Chem. Eur. J. 2012, 18, 4345

Negeshi Cross-‐Coupling

O

N N

O

i-Pr i-Pr

NC

Br

R1R ZnR

10 mol% NiCl2•diglyme13 mol % Ligand20 mol% TMEDA

THF-78 °C

NC

R

R1

NC

Ph NC

Ph

N

OO NC

Ph

NC

F

NC

OMe

77%92% ee 95%

85% ee

94%78% ee

99%93% ee

81%94% ee

NC

59%86% ee

NC

92%92% ee OMe

Choi, J.; Fu, G. C. J. Am. Chem. Soc. 2012, 134, 9102.


Oelke, A. J.; Sun, J.; Fu, G. C. J. Am. Chem. Soc. 2012, 134, 2966.

O

N N

OO

R1

Ar ZnI

10 mol% NiCl2(PCy3)213 mol % Ligand20 mol% TMEDA

DME/THF (1:1)10 °C

TMS

R1TMS

Ar1.5 equiv.O

OOMe

OMeMeO

TMSTMSTMS

OAc

ClF

OO

Cl

69%93% ee 81%

86% ee65%

84% ee


Br

n-BuTMS

Cl

n-BuTMS

O

n-BuTMS

O

OMe73%

89% ee78%

90% ee

O

n-BuTMS

O

O

O

n-BuTMS

O

O

O

n-BuTMS

O

O

9%60% ee

MeO MeO OMe

O

n-BuTMS

O

OOMe

OMeMeO33%

85% ee53%

88% ee56%

89% ee83%

90% eeOelke, A. J.; Sun, J.; Fu, G. C. J. Am. Chem. Soc. 2012, 134, 2966.

O

N N

O

LG

R1 Ph ZnI10 mol% NiCl2(PCy3)2

13 mol % Ligand

DME/THF (1:1)10 °C

TMSR1

TMS

Ph1.5 equiv.


Ms

F

I

O

MeO

91%96% ee

48%87% ee

74%91% ee

54%95% ee

52%84% ee

10 mol% NiBr2•glyme13 mol % LigandCsI (1.2 equiv)

DCM/dioxane-30 °C

Ar R

Br NN

O

t-BuZnI

n n

RAr

Binder, J. T.; Cordier, C. J.; Fu, G. C. J. Am. Chem. Soc. 2012, 134, 17003.


Binder, J. T.; Cordier, C. J.; Fu, G. C. J. Am. Chem. Soc. 2012, 134, 17003.

Kumada-‐Corriu-‐Tamao Cross-‐Coupling

Vechorkin, O.; Csok, Z.; Scopelli7, R.; Hu, X. Chem. Eur. J. 2009, 15, 3889.

X = I, 80%X = Br, 87%X = Cl, 4%

X = I, 78% X = I, 76% X = I, 0%

R2 MgClNIckamine (9 mol%)

THF-20 °C, 30 min

R1 X R1 R2N Ni

NMe2

NMe2

Cl


Vechorkin, O.; Proust, V.; Hu, X. J. Am. Chem. Soc. 2009, 131, 9756.

Ar MgCl

NIckamine (3 mol%)TMEDA (34 mol%)

THFr.t., 1 h

R1 X R1 ArN Ni

NMe2

NMe2

Cl(1.2 equiv.)

NC

O

Et2N

X = I, 80% X = I, 84%

Cl

X = Br, 76%

HO

X = Br, 76%(2.4 equiv of PhMgCl)

NO

F

X = I, 62%(60 mol% of O-TMEDA)

O

X = I, 0%

EtO

O

X = I, 75%(60 mol% of O-TMEDA)


NIckamine (5 mol%)3 equiv. O-TMEDA

THFr.t., 6 h

R1 XR1

N Ni

NMe2

NMe2

ClR2BrMgR2

t-Bu

OEt2N

TMSO

O

OO

X = I, 69 X = Br, 78%

X = Br, 83%

Vechorkin, O.;Godinat, A..; Scopelli7, R., Hu, X. Angew. Chem. Int. Ed. 2011, 50, 11777.


Vechorkin, O.;Godinat, A..; Scopelli7, R., Hu, X. Angew. Chem. Int. Ed. 2011, 50, 11777.

Sonogashira Cross-‐Coupling

Sonogashira, K. J. Organomet. Chem. 2002, 653, 46


n-octyl n-C6H13

X = I, 83%X = I, 84%

n-C6H13

X = Br, 73%with NaI (20 mol%)

n-C6H13


Cl

n-C6H13


OEtO

O

O

Br

NIckamine (5 mol%)CuI (3 mol%)

Cs2CO3dioxane

100 °C, 16 h

R1 XR1

N Ni

NMe2

NMe2

ClR2HR2

Vechorkin, O.; Barmaz, D.; Proust, V.; Hu, X. J. Am. Chem. Soc. 2009, 131, 12078


Vechorkin, O.; Barmaz, D.; Proust, V.; Hu, X. J. Am. Chem. Soc. 2009, 131, 12078

n-octyl n-C6H13

89%TMS

62%

n-C6H13

73%

O

O 4

OEtO

NIckamine (5 mol%)CuI (3 mol%)

TBAI (24mol%)

Cs2CO3 (1.4 equiv.)dioxane

140 °C, 16 h

R1 ClR1

N Ni

NMe2

NMe2

ClR2HR2

Heck-‐Type Cross-‐Coupling

Liu, C.; Tang,S.; Yuan, J.; Zheng, L.; Meng. L.; Lei,A. Angew. Chem. Int. Ed. 2012, 51, 3638.

O

OEt

O

OEt

O

HN

MeO F

77%

with: Ni(PPh3)4 (5 mol%) dppb (6 mol%) 60 °C

49%


89%


Ar

RBr

R'Y

O

Ni(PPh3)4 (x mol%)dppp (y mol%)

K2PO4 (2 equiv.)

tolueneT, 16h O

YR'

Ar

R

Heck-‐Type Cross-‐Coupling

Liu, C.; Tang,S.; Yuan, J.; Zheng, L.; Meng. L.; Lei,A. Angew. Chem. Int. Ed. 2012, 51, 3638.

Cross-‐Coupling of Aryl-‐Halide with Alkyl-‐Halide

Everson, D. A.; Shrestha, R.; Weix, D. J. J. Am. Chem. Soc. 2010, 132, 920

NiI2•xH2O (11 mol%)4,4'-di-t-butyl-2,2'-bipyridine (5 mol%)

o-(Ph2P)2C6H4 (5 mol%)Mn0 (2 equiv.)

DMPU60 °C, 36 h

RArAr X1R X2

BO

OC8H17

OEt

OC5H11

NAc

C8H17

X1= Br, X2 = I82%

X1= I, X2 = Br77% (T = 80 °C)

NH

Boc

X1= I, X2 = Br85%

X1= Br, X2 = I77%

X1= I, X2 = Br77%

(T = 80 °C, t = 36 h)

C8H17

X1= Br, X2 = I82%

Cross-‐Coupling of Alkyl-‐Halides with Allylic Acetates

Anka-‐Lufford, L. L..; Prinsell, M. R.; Weix, D. J. J. Org. Chem.. 2012, 77, 9989

NiCl2(dme) (5 mol%)L (5 mol%)

Mn0 (2 equiv.)

THF/DMA (3:1)40 °C, 18 h

Ar OAc Br Alkyl Ar Alkyl

N

N

N

t-Bu

t-Bu t-Bu

HPh

C5H11

C5H11

MeO

C5H11

C5H11

MeO

90% 79%78%

79% 66%

Cross-‐Coupling of Alkyl-‐Halides with Allylic Acetates

Anka-‐Lufford, L. L..; Prinsell, M. R.; Weix, D. J. J. Org. Chem.. 2012, 77, 9989

Conclusion

•  Cross-‐Coupling CSp3-‐CSp3: – Pd : β-‐H elimina7on – Ni : more or less easy

•  2 dis7nc7ves methods : – Pd : reten7on of configura7on – Ni : non reten7on

Nickel’Catalyzed’Cross1Coupling’...

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