transition metal catalyzed c h activation on the cmd...

Transition‐Metal‐Catalyzed C‐H Activation on the CMD Pathway

Reporter: Wenjun Miao2014‐3‐10

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2

3

4

5

Background

Direct Catalytic C‐H Bond Metallation of Arenes

The Catalytic Cross‐Coupling of Unactiviated Arenes

References

Mechanistic Work on the CMD Pathway

Contents

A X M B A BCatalyst

Reaction type 1

Ar Ar'

Ar B(OH)2

Ar' X

Ar ZnX

Ar' X

Ar MgX

Ar' X

Ar SiR3

Ar' X

Ar SnR3

Ar' X

Ar X

Ar X

Negishi Coupling

Stille CouplingSuzuki Coupling

Hiyama Coupling

Kumada Coupling

Ullmann Reaction

Both aromatic compounds must be preactivated

Background

Background

A X H B A BCatalyst

Reaction type 2

A H M B A BCatalyst

Direct Arylation of Unactivated Arenes

EducationPh.D.: University of Toronto, 2002 (Supervisor: Prof. Mark Lautens)

M.Sc.: University of Toronto, 2000 B.Ed.: University of Saskatchewan, 1995

Employment History2007‐2009 Associate Professor with tenure, University of Ottawa

2002‐2007

Assistant Professor, University of Ottawa 1998‐2002 Graduate Student in Organic Chemistry, University of Toronto

1995‐1996 High School Teacher, Ecole Canadienne Française/St. Joseph HS Saskatoon, SK

Keith Fagnou1971‐2009

Background

Catalytic Oxidative Arene Cross‐Coupling

Background

X

Y

X

R

X = O, CO, NHY = Br, I

10% mol Pd(OAc)2

K2CO3, DMA

R

Ames,

D. E.; Opalko,

A.

Tetrahedron

1984,

40,

1919.Ames,

D. E.; Opalko,

A.

Synthesis

1983,

234.


Campeau, L.‐C.; Parisien, M.; Leblanc, M.; Fagnou, K.

J. Am. Chem. Soc.

2004,

126, 9186

NO

XN

1) Pd(OAc)2, P(t-Bu)3-HBF4K2CO3, PhMe,110oC

2)Pd/C, HCOONH4MeOH, rt

RR

RR


Fagnou, K.

J. Am. Chem. Soc.

2005,

127, 18020

Lafrance, M.; Rowley, C.N.; Woo, T. K.; Fagnou, K.

J. Am. Chem. Soc.

2006,

128, 8754

Direct Arylation of Unactivated Arenes Unprecedented Reactivity from a Palladium‐Pivalic Acid Co‐Catalyst SystemPivalic Acid as a Catalytic Proton Shuttle and a Key Element in Catalyst Design

Pd(OAc)2 (3 mol%)Ligand (3 mol%)

t-BuCO2H (30 mol%)

K2CO3 (2.5 equiv.)DMA/C6H6/C6H5OMe(1.2:0.5:0.5), 1200C100% conversion

F

BrA o, m, p-C

o, m, p = 22: 3: 1

A: C = 1: 11

F


LnPd(0)

PdLn(Ar)Br

ArBr

KBr

OH

O

O

OK2CO3 KHCO3

K

Pd OO

PR3Ar

PdR3PH

O O

PdR3PAr

OOH

PdAr(PR3)

Ar

O

OH

PdR3P

Ar

ArBr + K2CO3

KBr + KHCO3

HPh

Pathway A

Pathway B

Direct Catalytic C‐H Bond Metallation

of Arenes

Lafrance, M.; Fagnou, K.

J. Am. Chem. Soc.

2006,

128, 16496

The Catalytic Cross‐Coupling of Unactiviated

Arenes

Campeau, L.‐C.; Schipper, D.; Fagnou, K.

J. Am. Chem. Soc.

2008,

130, 3266

N

O

H

H

H

N

O

N

O

Ar

Ar

excess

R R' Pd(II) catalyst

N

O

Roxidant(- 2H+)

R

R

R'

1 major

2

3

Stuart, D. R.; Fagnou, K.

Science

2007,

316, 1172


Arenes

Entry Indole Arene T (0C) mol % Pd % Conv. 1:2:3

1

2

3

4

5

6

7

8

9

% Yield 1

NAc

NAc

NAc

NAc

NAc

NAc

NAc

NAc

NAc

AcO

H3CCl

Cl

MeO

O

MeO

140 10 100 11.2:1:0.4 84

140 10 100 8110:1:0.6

110*

110*

140

140

140

140

140

10

10

10

20

20

20

20

83

81

100

80

nd

72

nd

6.5:1:0

5.7:1:0

10.5:1:0.3

2.8:1:0

10.4:1:0.4

6.7:1:0

9.9:1:0

63

61

74

54

45

52

42

CH3

H3COMe

MeOF

F


Arenes


Science

2007,

316, 1172

N

H

H

CH3

CH3

H

RN

H

R

CH3

CH3

N

H

R CH3

CH3

Pd(II) cat.

Cu(OAc)2oxidantR = Ac

AgOAcoxidantR = Piv

C-3 oxidativearylation

C-2 oxidativearylation

Stuart, D. R.; Villemure, E; Fagnou, K.

J. Am. Chem. Soc.

2007,

129, 12072

The Catalytic Cross‐Coupling of Unactiviated Arenes


Arenes


Science

2007,

316, 1172

NR

H NRH

R' R'

exess

Pd(TFA)2 (10%)AgOAc

PhH: PivOH1100C

N

OMe

O

CH3

NCH3

O

CH3

N

OMe

O

OMe

N

OMe

O

CH3

N

O

64% 68% 66%

67% 53%

Stuart, D. R.; Villemure, E; Fagnou, K.

J. Am. Chem. Soc.

2007,

129, 12072


Arenes


A. D. Ryabov, I. K. Sakodinskaya, A. K. Yatsimirsky. J. Chem. Soc., Dalton Trans. 1985,

2629.

S

N

Hb

Hc O

Ha

S

N

Ha

Hb O

S

NHc

HaHb

N

Hc

Hb

Ha

O

S Ha

Hb

O Ha

HbN

N N

Ha

Hb

N

Ha

Hb

Hc

N

H

CH3 N

H

O

OMe

FF

FF

F

H H

SH 26.5

Hb

SH

F

23.3

22.7

22.5

23.8

30.5

31.1

27.3 23.6

29.7

26.3

25.6

29.9

25.3

28.721.4

30.7

22.5

30.9

27.1

23.2 22.9

22.3 33.9

22.6

1 2 3 4

5 6 7 8

9 10 11 12

13 14

Calculated activation barrier for the CMD pathway.


S

S

F

S

S

F

Ar

ArPd(OAc)2 / PCy3HBF4K2CO3, DMA, 1000C

Ar-Br (0.1 equiv.)PivOH (30 mol%)

Ar = 4-C6H4CO2Et

A

B

A: B = 1:>20

Gorelsky, S.; Lapointe, D.; Fagnou, K.

J. Am. Chem. Soc.

2008,

130, 1084


Gorelsky, S.; Lapointe, D.; Fagnou, K.

J. Am. Chem. Soc.

2008,

130, 1084


Gorelsky, S. I. Coordination Chemistry Reviews

2013, 257, 153.

References(1) Winstein, S.; Traylor, T. G. J. Am. Chem. Soc. 1955, 77, 3747.(2) García-Cuadrado, D.; Braga, A. A. C.; Maseras, F.; Echavarren, A. M. J. Am. Chem. Soc.

2006, 128, 1066.(3) Lafrance, M.; Rowley, C. N.; Woo, T. K.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 8754.(4) García-Cuadrado, D.; de Mendoza, P.; Braga, A. A. C.; Maseras, F.; Echavarren, A. M. J.

Am. Chem. Soc. 2007, 129, 6880.(5) Stuart, D. R.; Fagnou, K. Science 2007, 316, 1172.(6) Gorelsky, S. I.; Lapointe, D.; Fagnou, K. J. Am. Chem. Soc. 2008, 130, 10848.(7) Lapointe, D.; Fagnou, K. Chem Lett. 2010, 39, 1118.(8) Potavathri, S.; Pereira, K. C.; Gorelsky, S. I.; Pike, A.; LeBris, A. P.; DeBoef, B. J. Am.

Chem. Soc. 2010, 132, 14676.(9) Rousseaux, S.; Gorelsky, S. I.; Chung, B. K. W.; Fagnou, K. J. Am. Chem. Soc. 2010, 132,

10692.(10) Sun, H.-Y.; Gorelsky, S. I.; Stuart, D. R.; Campeau, L.-C.; Fagnou, K. J. Am. Chem. Soc.

2010, 75, 8180.(11) Ackermann, L. Chem Rev. 2011, 111, 1315.(12)

Anand, M.; Sunoj, R. B. Org Lett. 2011, 13, 4802.(13) Baudoin, O. Chem Soc Rev. 2011, 40, 4902.(14) Gorelsky, S. I.; Lapointe, D.; Fagnou, K. J. Org Chem. 2011, 77, 658.(15) Kitahara, M.; Umeda, N.; Hirano, K.; Satoh, T.; Miura, M. J. Am. Chem. Soc. 2011, 133,

2160.(16) Théveau, L.; Verrier, C.; Lassalas, P.; Martin, T.; Dupas, G.; Querolle, O.; Van Hijfte, L.;

Marsais, F.; Hoarau, C. Chem. Eur. J. 2011, 17, 14450.(17) Wencel-Delord, J.; Droge, T.; Liu, F.; Glorius, F. Chem Soc Rev. 2011, 40, 4740.

(14) Gorelsky, S. I.; Lapointe, D.; Fagnou, K. The J. Org. Chem. 2011, 77, 658.(15) Kitahara, M.; Umeda, N.; Hirano, K.; Satoh, T.; Miura, M. J. Am. Chem. Soc. 2011, 133,

2160.(16) Théveau, L.; Verrier, C.; Lassalas, P.; Martin, T.; Dupas, G.; Querolle, O.; Van Hijfte, L.;

Marsais, F.; Hoarau, C. Chem. Eur. J. 2011, 17, 14450.(17) Wencel-Delord, J.; Droge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev. 2011, 40, 4740.(18) Zhang, S.; Shi, L.; Ding, Y. J. Am. Chem. Soc. 2011, 133, 20218.(19) Gorelsky, S. I. Organometallics 2012, 31, 4631.(20) Gorelsky, S. I. Organometallics 2012, 31, 794.(21) Cong, X.; Tang, H.; Wu, C.; Zeng, X. Organometallics 2013, 32, 6565.(22) Figg, T. M.; Wasa, M.; Yu, J.-Q.; Musaev, D. G. J. Am. Chem. Soc. 2013, 135, 14206.(23) Gorelsky, S. I. Coo. Chem. Rev. 2013, 257, 153.(24) Mercier, L. G.; Leclerc, M. Acc. Chem. Res. 2013, 46, 1597.

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