Organo-metal cooperative catalysis ♦ 3rd year seminar Tiffany Piou Supervisors: Dr. Luc Neuville and Prof. Jieping Zhu 25.01.12 1.

1

Organo-metal cooperative catalysis

♦

3rd year seminar

Tiffany Piou

Supervisors: Dr. Luc Neuville and Prof. Jieping Zhu

25.01.12

2

Transition metal catalysis

One of the most useful and powerful tool in organic chemistry.

Advantages:

- Chemoselectivity- Regioselectivity- Stereoselectivity- High yield- Reproducibility- Low catalyst loading

Examples of transition metal reactions:

- Cross-coupling - Hydroformylation - Alkene and alkyne metathesis- Hydrogenation- Cyclopropanation - Hydroamination- Hydroesterification- Hydrocarboxylation- Pauson-Khand reaction- Isomerisation of olefins- Hydrocyanation

Transition Metals for Organic Synthesis: Building Blocks and Fine Chemicals (Eds.: M. Beller, C. Bolm), Wiley-VCH, Weinheim, 2nd ed., 2004, vol. 1 and 2.

3

Organocatalysis

Major topic in organic chemistry

Access to enantiomerically enriched molecules

Explosion of new organocatalysts

NH O

OP

O

OH

NH

NO

tBu

Ar

Ar

Ph Ph

OTMS

N

MeO

HON

S

NH

NH

R2

R1

N NR3 R2

NH

CO2H

Main advantages:

- Not expensive- Easily accessible- Stable to air and moisture

Enantioselective Organocatalysis: Reactions and Experimental Procedure (Ed,: P. I. Dalko), Wiley-VCH, Weinheim, 2007.

4

Cooperation between transition metal and organocatalyst

Concept introduced by Krische in 2003.

R

OOCO2Me PBu3 (100 mol%),

Pd(PPh3)3 (1 mol%)

tBuOH, 60°C.R

O

64-92%n

n

R

O

nBu3P

PdII

PBu3

Pd0

CO2OCH3

R

O

Bu3P

HPd0

OCH3

Pd0

PBu3

CH3OH

Combine Morita-Baylis-Hillman type reaction and Tsuji-Trost reaction

Use of “non classical” electrophilic partner

Open new perspectives

B. G. Jellerichs, J.-R. Kong, M. J. Krische J. Am. Chem. Soc. 2003, 125, 7758-7759.

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Cooperation between transition metal and organocatalyst

Metal +

Organocatalyst

Cooperative catalysis

Unprecedented transformations not currently possible with the transition metal or the organocatalyst alone.

New tool in organic chemistry

Problem: compatibility?

C. Zhong, X. Shi, Eur. J. Org. Chem. 2010, 2999-3025.Z. Shao, H. Zhang, Chem. Soc. Rev. 2009, 38, 2745-2755.

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ACatalyst 1

+Catalyst 2

BA Catalyst 1

B

CCatalyst 2

Two different types of cooperation

The two catalysts operate simultaneously

The two catalysts operateSuccessively in a “one pot” fashion


7

ACatalyst 1

+Catalyst 2

BA Catalyst 1

B

CCatalyst 2

Two different types of cooperation

The two catalysts operate simultaneously

The two catalysts operateSuccessively in a “one pot” fashion


8

Cooperative Reactions:

Transition Metal+

Organocatalyst

Aminocatalysis

Brönsted acid/base

Lewis Base

Bifunctional catalystNHC organocatalyst


9

Transition metal with aminocatalysis

N

R1

R2

E R1

N

R2

Nu

Enamine catalysis Iminium catalysis

LUMO loweringHOMO raising

Functionnalization of carbonyl compounds

Pioneering work by Barbas, List and MacMillan

Amine activations are the most studied organocatalytic system

One of the most popular strategies in cooperative catalysis

S. Mukherjee, J. W. Yang, S. Hoffmann, B. List, Chem. Rev. 2007, 107, 5471-5569.

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First example, Cordova et al. in 2006,

Intermolecular α-allylation

H

N

R

RM

AcO R3 R2

O

R1

Pd(PPh3)4 (5 mol%)

(10-30 mol%) DMSO, rt.N

H

R2

O

R1

R3

up to 95% yield

Breit et al. in 2009,

HOR3

R1

O

R2

Pd(-allyl)Cl2 (2.5 mol%)

XantPhos (5.0 mol%)

(DL)-proline (30 mol%)

DMSO, 70 °C, 20 h

O

R1

R2

R3

NH

HOOC

O

H

H O

O

N

H2O

PdL

L

Pd

LLNO2C

tight ion pair

No stereoselectivity

I. Ibrahem, A. Cordova, Angew. Chem. Int. Ed. 2006, 45, 1952-1956.I. Usui, S. Schmidt, B. Breit, Org. Lett. 2009, 11, 1453-1459.

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Saicic et al. in 2007,

Intramolecular α-allylation

H

N

R

RM

O

H

Br

EtO2C CO2Et

(R)-(BINAP)Pd (7 mol%),pyrrolidine,

Et3N, THF, -20 °C

HO

EtO2C CO2Et

y = 40%, 91% ee

O

H

OP(O)(OEt)2

EtO2C CO2Et

(R)-(Ph-MeOBIPHEP)Pd (10 mol%),pyrrolidine,

Et3N, THF, -20 °C

HO

EtO2C CO2Et

y = 76%dr = 7.4:1, 98% ee

MeO

MeO

PPh2

PPh2

(R)-(Ph-MeOBIPHEP)

Chiral amine catalysts tested failed

2009,

F. Bihelovic, R. Matovic, B. Vulvovic, R. N. Saicic, Org. Lett. 2007, 9, 5063-5066.B. Vulvovic, F. Bihelovic, R. Matovic, R. N. Saicic, Tetrahedron 2009, 65, 10485-10494.

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Enamine addition to activated alkyneH

N

RR

M

H

O

R1

R2NH2

O

R3

R4

Proline (10 mol%)AgOTf (10 mol%)

EtOH, 50-60 °CNH

R4

O

R3

R1

H

N

R1

R2

Ag

N

R3

R4

HO2C

up to 95%

Multicomponent reaction developed by Wu’s group in 2007,

O

R1

R2

EWG EWG

R3

pyrrolidine (20 mol%)ps-BEMP (10 mol%)

Cu(OTf)2 (5 mol%)PPh3 (20 mol%)

MeOH, rt

R1

O R3

R2EWG

EWG

N

R1

R2

EWG EWG

R3

N

R1

R2

[Cu]

EWG EWG

71-82%

Tandem reaction published by Dixon’s,

Q. Ding, J. Wu, Org. Lett. 2007, 9, 4959-4962.T. Yang, A. Ferrali, L. Campbell, D. J. Dixon, Chem. Commun. 2008, 2923-2925.

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Enamine induced enantioselective cooperative reaction

R1

OH

R2

O

O

R2

R1

O

R2

R1

93% yieldsyn/anti 2.0-3.0:1

up to 99% ee

chiral amine (5 mol%)[Ru] (5 mol%)

NH4BF4 (10 mol%)toluene, rt

NH

ArAr

OTMS

Ar = 3,5-(CF3)2C6H3

Ru RuS

S

Cp*Cp*

MeMe

Cl Cl

[Ru]

R1 H

R1

OH

[Ru]

H

OH

R1

vinylidene complex

-H2O

N

R2

[Ru]

N

[Ru]

[Ru]

H

OO

R2

R1

-H2O

[Ru]

R1 H

N

OSiMe3

ArAr

minor

[Ru]

H R1

N

OSiMe3

ArAr

major

Nishibayashi et al in 2010,

M. Ikeda, Y. Miyake, Y. Nishibayashi, Angew. Chem. Int. Ed. 2010, 49, 7289-7293.

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Enamine catalysis with SOMO photoredox catalysis

Br FGH

O

Y

fluorescent lightMacMillan's catalyst

Ru(bpy)2Cl2, 2,6-lutidineDMF, rt

H

O

Y

R

FG

up to 92% yieldup to 99% ee

R

NH

NOMe

Me

tBu

MacMillan's catalyst

[Ru]2+

photoredox catalyst

[Ru]2+*

h

[Ru]+

oxidant

SET

FG Br

FG

.

Brreductant

N

NOMe

Me

tBu

R

N

NOMe

Me

tBu

FG

R

SET

FG

N

NOMe

Me

tBu

FG

R

NH

NOMe

Me

tBu

O

HR

O

H FG

R

A. Nicewicz, D. W. C. MacMillan, Science 2008, 322, 60-77.

SET = single electron transfer

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Transition Metal+

Organocatalyst

Aminocatalysis

Brönsted acid/base

Lewis Base


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Chiral Brönsted-acid/base with metal activated substrates

Chiral Brönsted acid/base catalyst: a powerful strategy.

In combination with transition-metal, 3 approaches:

OP

O

OR* OR*

H

Nu

E+

[M]

Asymmetric Counter Anion Directed Catalysis (ACDC)

R

X

H

H X*

[M] Nu

Chiral Brönsted Acid Activation

R3NH

Nu

[M] E

Chiral Brönsted BaseInduced Nucleophiles

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OP

O

OR* OR*

H

Nu

E+

[M]


R

X

H

H X*

[M] Nu


R3NH

Nu

[M] E


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Asymmetric Counter-Anion-directed catalysis Strategy (ACDC)

First example proposed by Toste et al,

OP

O

OR* OR*

H

Nu

E+

[M]

NHSO2Mes

R3 R4

R1

R2

PhMe2OAuCl (5 mol%)Ag/(R)-TRIP (5 mol%)

PhH, 23 °C, 48 h

NR1

R2

SO2MesH

R3R4


R3 R4

R1

R2

OH

R5 R6

PhMe2OAuCl (5 mol%)Ag/(R)-TRIP (5 mol%)

PhH, 23 °C, 48 h

OR1

R2

H

R3R4

R5

R6


O

OP

O

OAg

iPr

iPriPr

iPr

iPr iPr

Ag/(R)-TRIP

G. L. Hamiltion, E. J. Kang, M. Mba, F. D. Toste, Science 2007, 317, 496-499.

[LAuX] Ag Y [LAu] Y AgX

chiral ion pair

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Enantioselective α-allylation of aldehyde via ACDC strategy O

PO

OR* OR*

H

Nu

E+

[M]

HO

R3

R4R1 CHO

R2

Pd(PPh3)4 (1.5 mol%)(S)-TRIP (3.0 mol%)

(40 mol%)

MS 5A, toluene, 40 °Cthen HCl (2N)

R1 CHO

R2

R3

R4

Ph NH2

Ph

97% yielder up to 99.8:0.2

O

POR*HO

OR*

OH

HO

P

O

OR*OR*

OH

-H2OPd

Ph3P PPh3

O

POR*

OR*

O

O

Pd

PO

OR* OR*

HN Ph

Ph

R2

R1 H

Pd(0)

Ph

NH

PhPh

NH2Ph

Ph

NH

H

PhO

H

Ph -H2O

+H2O

Ph

CHO

G. Jiang, B. List, Angew. Chem. Int. Ed. 2011, 50, 9471-9474.

List et al.,

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OP

O

OR* OR*

H

Nu

E+

[M]


R

X

H

H X*

[M] Nu


R3NH

Nu

[M] E


21

R

X

H

H X*

[M] Nu

Chiral Brönsted acid activation

Asymmetric alkynylation of α-imino esters proposed by Chan et al.:

H CO2Et

NPMP

Ph

Cu(OTf)2 0.5 C6H6

L1 (10 mol%)

DCM, 10 h Ph

CO2Et

NHPMP


H CO2Et

NPMP

Ar

Cu(OTf)2 0.5 C6H6

L2 (10 mol%)

DCM, 10 h Ar

CO2Et

NHPMP


N

ON

N

O

PhN

ON

N

O

Ph

L1

L2

Limited scope!

J.-X. Ji, J. Wu, A. S. C. Chan, Proc. Natl. Acad. Sci. USA 2005, 102, 11196-11200.

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R

X

H

H X*

[M] Nu

Chiral Brönsted acid activation: sp carbon nucleophile

H CO2Et

NPMP

R

R

CO2Et

NHPMP


cat. 1 (10 mol%)AgOAc (5 mol%)

toluene, rt, 10-12 h

O

OP

O

OH

Ar

Ar

Ar

1H CO2Et

NPMP

R'[Ag]OR*

P

O

OR*O

H

H R2

NR1

R

CuPF6 (2.5 mol%), P(o-tolyl)3Boc-proline (10 %mol)

DCM, 0°C, 72 hR2

NH

R3

R1

H R2

NR1

HO

O

NBoc


Rueping et al. 2007,

- Inexpensive catalyst- Large scope- Excellent ee

Arndtsen et al.,

M. Rueping, A. P. Antonchick, C. Brinkmann, Angew. Chem. Int. Ed. 2007, 46, 6903-6906.Y. Lu, T. C. Johnstone, B. A. Arnsdtsen, J. Am. Chem. Soc. 2009, 131, 11284-11285.

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Chiral Brönsted acid activation: Rh mediated-carbene nucleophile

R

X

H

H X*

[M] NuN2

Ar1 CO2R1R2OH

H

N

Ar3

Ar2 Rh2(OAc)4 (2 mol%)cat. 1 (2 mol%)

DCM, -20 °C Ar3

Ar1

NHAr2

R2OR1O2C

OO

PO

OH

Ar

Ar

Ar

cat. 1

RhLn

N2

Ar1 CO2R1

RhLn

Ar1 CO2R1

OR2H

Ar1 CO2R1

RhLn

OR2H

Ar1 CO2R1

H

N

Ar3

Ar2 H

NAr2

Ar3

O

PHO OR*

OR*

OP

O

OR*OR*

N

Ar3H

H

OP

O

R*O OR*

HO

R2

CO2R1Ar1

Ar3

Ar1

NHAr2

R2OR1O2C

O

PHO OR*

OR*

up to 98% yieldup to >99:1 drup to >99% ee

W.-H. Hu, X.-F. Xu, J. Zhou, W.-J. Liu, H.X. Huang, J. Hu, L. P. Yang, L.-Z. Gong, J. Am. Chem. Soc. 2008, 130, 7782-7783.

24

Enantioselective hydrogenation of imine R

X

H

H X*

[M] Nu

R1

NPMP

R1 = aryl, alkyl.

S-TRIP (1 mol%), [Fe] (5 mol%)

50 bar H2, 65 °C, toluene, 24 h

R1

HNPMP

OCFe

OCH

TMS

TMSOH

Knölker's complex

R1

NPMP

P

OR*R*O

O

OH

R1

NPMPH

P

OR*R*O

O

O

[FeH2]

[Fe]

H2

R1

HNPMP


An alternative to the Hantzsch dihydropyridine

Beller’s group in 2011,

S. Zhou, S. Fleisher, K. Junge, M. Beller, Angew. Chem. Int. Ed. 2011, 50, 5120-5124.

25




OP

O

OR* OR*

H

Nu

E+

[M]


R

X

H

H X*

[M] Nu


R3NH

Nu

[M] E


26

Me

NO2

CO2Et

NPMP

CO2Et

quinine (20 mol%)(R)-Ph-BOX-Cu(OTf)2 (20 mol%)

DCMMe HO2N

tBuO2C

NHPMP

CO2Et

N

MeO

NHO

O

N N

O

Ph PhCu

quinine

(R)-Ph-BOX-Cu(OTf)2

Me

NO2

CO2Et

NR1

R2

R3

H N

H

OEt

O

PMP CuH2N NH2

*

yield 90%dr 14:1ee 98%

R3NH

Nu

[M] E

Chiral Brönsted base and transition-metal Lewis acid

Enantioselective aza-Henry reaction,

K. R. Knudsen, K. A. Jorgensen, Org. Biomol. Chem. 2005, 3, 1362-1364.

27

O

R1

O

R2

cat.1 (20 mol%)CuOTf 0.5 C6H6 (5 mol%)

DCM, rt, 1-4 days

O

R1

O

R2


N

NH

NHO

F3C CF3

N

cat. 1

Bronsted/Lewis base

hydrogen donor

2 distinct roles: - deprotonation of the enolate - ligand for copper

O

Ph

O

CO2Et

D

Ph

ODCu

L

conditions

O

Ph

DCuL

EtO2C

EtO2C

HO

Ph

D

EtO2C

Chiral Brönsted base and transition-metal Lewis acid R3NH

Nu

[M] EEnantioselective Conia-ene reaction

T. Yang, A. Ferrali, F. Sladojevich, L. Campbell, D. J. Dixon, J. Am. Chem. Soc. 2009, 131, 9140-9141.

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Transition Metal+

Organocatalyst

Aminocatalysis

Brönsted acid/base

Lewis Base


29

Organic Lewis base with transition-metal activated electrophiles

Few examples probably because of compatibility problems

R

OOCO2Me PBu3 (100 mol%),

Pd(PPh3)3 (1 mol%)

tBuOH, 60°C.R

O

64-92%n

n

EWG

LB = PR3, NR3.

LB

EWG

LB

E [M]

Activation mode of Lewis base

B. G. Jellerichs, J.-R. Kong, M. J. Krische J. Am. Chem. Soc. 2003, 125, 7758-7759.

Krische in 2003,

30

Organic Lewis base catalysed tandem reaction

CHO

R2

R3NH2

O

R4

AgOTf (10 mol%)PPh3 (20 mol%)

THF, 70 °C NR3

O

R4

R1

R1 R2

H2O

R2

R1N

R3[Ag] N

R3

[Ag]

R2R1

NR3

[Ag]

R2R1

PPh3

O

R4

PPh3

[Ag]

PPh3

O

R4H

AgOTfPPh3

45-70% yield

Wu et al. reported a 3 components reaction,

S. Ye, J. Wu, Tetrahedron Lett. 2009, 50, 6273-6275.

31


Transition Metal+

Organocatalyst

Aminocatalysis

Brönsted acid/base

Lewis Base


32

Bifunctional catalyst

Bifunctional catalyst

OrganocatalystMetal Ligand

New generation of catalyst

New strategy for cooperative catalysis

Enhance the compatibility between the metal and the organocatalyst

33

Bifunctional organocatalyst in cooperation with transition metal

Jun and co-workers,

Ar H

O

Ph

Rh(PPh3)3Cl (5 mol%)2-amino-3-picoline (20 mol%)

aniline (60 mol%)benzoic acid (6 mol%)

toluene, 150 °C, 24 hAr

O

R

up to 98%

C.-H. Jun, H. Lee, H. Lee, J.-B. Hong, Angew. Chem. Int. Ed. 2000, 39, 3070-3072.

NH2NMetal ligand

Organocatalyst

Ar H

O

Ar H

N N

NH2N

Ar

N N

RhL

LH

ClAr

N N

RhL

HCl

Ph

Ar

N N

RhLCl

R

Ar

N N

RRh(PPh3)3Cl

Ar

O

R

34

Bifunctional organocatalyst in cooperation with transition metal

O

R3R2

R1CHO

Cu(SbF6)2 (20 mol%)L1 (20 mol%)

THF, rt, 24-72 h

O

R3R2

R1

OH

NHN NH

O

HN

O

NHBoc

NHN NH

O

N

O

NHBoc

Cu

O

H R1

NHN NH

O

N

O

NHBoc

Cu

O

R1 H

disfavoredfavored

Tridentate ligand

organocatalystup to 96% yield

up to 99:1 drup to 99% ee

Maximize the compatibility between the Lewis base and Lewis acid

Wang et al,

Z. Xu, P. Daka, I. Budik, H. Wang, F. Q. Bai, H.-X. Zhang, Eur. J. Org. Chem. 2009, 4581-4585.

35


Transition Metal+

Organocatalyst

Aminocatalysis

Brönsted acid/base

Lewis Base


36

R H

O

N N ArAr

R

O

NHC-mediated reactions

R H

O conjugate umpolung

N N ArAr

R

OH

N

NAr

Ar

extended Breslow intermediate

R

OH

N

NAr

Ar

Homoenolate

R

OH

N

NAr

ArE

E

Tautomerisation

R

O

N

NAr

ArE

NuR

O

Nu

E

Bode and Glorius in 2004,

S. Sohn, E. L. Rosen, J. W. Bode, J. Am. Chem. Soc. 2004, 126, 14370-14371.C. Burstein, F. Glorius, Angew. Chem. Int. Ed. 2004, 43, 6205-6208.V. Nair, R. S. Menon, A. T. Biju, C. R. Sinu, R. R. Paul, A. Josea, V. Sreekumarc, Chem. Soc. Rev. 2011, 40, 5336-5346.

Tool to develop enantioselective tandem reaction

Application in cooperative catalysis, but compatibility?

37

NHC-catalysed cooperative reaction

Scheidt et al. in 2011,

R1

O

H

NHC catalyst (20 mol%)Ti(OiPr)4 (5 equiv.)

DBU (40 mol%)iPrOH, THF, 23 °C

R2

O

O

OMe

R1R2

OiPr

O

OiPrO

HO

H

52-85% yield20:1 dr

91-99% ee

R2

O

N N

N

Ar

O

H

HR1

OO

MeOC-C bondformation

(iPrO)nTi

R2

O

N N

N

Ar

O

H

HR1

OO

MeO

(iPrO)nTi

R2

O

N N

N

Ar

O

H

HR1

OO

MeO

(iPrO)nTi

protonation/tautomerization/

aldol

block the front faceof NHC-enal

The Lewis acid coordinate and activate the α-ketoester

New class of electrophiles for NHC-catalysed annulation

D. T. Cohen, B. Cardinal-David, K. A. Scheidt, Angew. Chem. Int. Ed. 2011, 50, 1678-1682

38

Conclusion

Cooperative catalysis between transition metal and organocatalyst attracted much interest:

- Successfully promoting a variety of transformations

- Different combinations of metal and organocatalyst

- Development of new reactions

To be continued …

Organo-metal cooperative catalysis ♦ 3rd year seminar Tiffany Piou Supervisors: Dr. Luc Neuville and Prof. Jieping Zhu 25.01.12 1.

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transition metal catalysisone

cooperative reactions

catalysts operatesuccessively

different types of cooperation

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organic chemistryproblem

new tool

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