Colloque Chimie durable

18 et 19 septembre 2012 - Ecole Normale Supérieure de Lyon

Environmentally friendly catalysis using polydentate ligands: low-loading palladium catalysts and copper-adducts

for (C−H, or N−H) and (C−Cl, or C−Br) functionalization

Jean-Cyrille Hierso

Dominique Lucas Henri Doucet

Institut de

Chimie Moléculaire

UMR 6302

Institut des

Sciences Chimiques

UMR 6226

2

Admitted “Green” chemistry principles

1. Prevention

2. Atom Economy Synthetic methods should be designed to maximize the incorporation of materials into the final product.

3. Less Hazardous Chemical Syntheses

4. Designing Safer Chemicals

5. Safer Solvents and Auxiliaries

6. Design for Energy Efficiency

7. Use of Renewable Feedstocks

8. Reduced Derivatization Unnecessary derivatization should be minimized or avoided.

9. Catalysis Catalytic reagents, as selective as possible, are preferred to stoichiometric reagents.

10. Design for Degradation

11. Real-time analysis for Pollution Prevention

12. Inherently Safer Chemistry for Accident Prevention

13. It is better to understand what you are doing than not...

Some issues addressed (or at least attempted !) in this ANR program…

3

• R. B. Bedford et al. Chem. Commun. 1998, 2095.

• W. A. Herrmann et al. Angew. Chem. Int. Ed. EngI. 1995, 34, 1844.

• H. Doucet, M. Santelli et al. Chem. Commun. 2001, 325.

M. Beller et al. Angew. Chem. Int. Ed. EngI. 1995, 34, 1848.

Pd

P

oTol oTol

O

O

OPd

O P

oToloTol

PCy2 P(t-Bu)2

Ph2PPh2P

PPh2PPh2

Pd

Cl

PdCl P

O

OArArO

PO

ArO OAr

Ar = 2,4-(t-Bu)2C6H3

t-Bu

t-Bu

t-Bu

t-Bu

R. B. Bedford et al. Tetrahedron Lett. 1998, 39, 9793.

• S. L. Buchwald et al. Angew. Chem. Int. Ed. EngI. 1999, 38, 2413.

H. Doucet M. Santelli et al. J. Org. Chem. 2001, 66, 5923.

Milestones in low-loading catalysis

S. L. Buchwald et al. J. Am. Chem. Soc. 1999, 121, 9550.

Heck 100% (0.5x10-3%); Suzuki 74% (10-3%)

Heck 57% (10-5%); Suzuki 100% (10-4%)

Suzuki 91% (10-6%)

Heck 78% (10-6%); Suzuki 96% (10-6%)

J.-C. Hierso et al. Eur. J. Inorg. Chem. 2007, 3767: palladium cross-coupling, a review.

Ferrocene platform for implantation of phosphorus donors

Modular approach for library

building

4

“ Novel catalytic effects from cooperation of more than two donor atoms ? “

…what can be found beyond hemilability and chelating effects ?

5

PPh2

PPh2

Fet-Bu

Ph2P

PPh2

PPh2

Fe

t-Bu

P(i-Pr)2

PPh2

PPh2

Fet-Bu

PO

O

PPh2

PPh2

Fe

Me

Me

Me PPh2

Me

Me

Me

Me

PPh2

PPh2

Fet-BuPPh2

PPh2

Fe

Me

Me

Me

PPh2Fe

Ph2PPPh2

PPh2

Fet-Bu

CHO

PPh2

Me

Fe

Me

Me

Me PPh2

Me

Me

Me

Me

PO

O

Fe

PO

O

PO

O

Fe

PPh2

PR2

Fet-Bu

PR2

t-Bu

R = Ph, Me

Fu

PPh2

PPh2

Fe

Me

Me

Ph2P Me

Me

Ph2P

Me

Me PPh2

PPh2

Fe

t-Bu

PPh2

t-Bu PPh2

FePh2P

Ph2P PPh2

PPh2PPh2

PPh2

Fe

t-Bu

PPh2

PPh2

Polyphosphines built on ferrocene backbone

J.-C. Hierso et al. Chem. Soc . Rev. 2007, 36, 1754. A 1st generation library

6

XR1

X = Br, Cl

R1R2

R2

H

R1 R2

R1R2

R2

H

(HO)2B R2

Pd/L2 Pd/L1

L2 = PPh2

PPh2

Fet-Bu

(i-Pr)2P

L1 = PPh2

PPh2

Fet-Bu

PPh2

t-Bu PPh2

TONs up to 1,000,000

TONs up to 150,000

TONs up to 250,000

Performances in C–C bond formation at 10-1 to 10-4 mol%

J.-C. Hierso, H. Doucet et al., Organometallics, 2003, 22, 4490.

J.-C. Hierso, V. V. Ivanov , H. Doucet et al., Org. Lett., 2004, 6, 3473.

J.-C. Hierso et al. Tetrahedron. 2005, 61,975.

H. Doucet, J.-C. Hierso, Angew. Chem. Int. Ed. 2007, 46, 834.

Heck and Sonogashira protocols: inspiring C–H functionalization

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Cl

Br

I

H

Aromatics molecular mass

MH =1

MCl=35

MI =127

MBr = 80

Mw = 78

Mw = 112

Mass loss

Mw = 157

Mw = 204

Mass loss percent

1.28 %

31.25 %

50.96 %

62.25 %

• Mass loss during coupling processes with benzene and halobenzenes

Csp2–Csp2 bond formation with heteroaromatics

see Adv. Synth. Catal. 2008, 350, 2183 and ref. therein

+ Pd

• Stoichiometric metallic waste is produced • Necessary preparation of organometallics for Suzuki, Stille, Negishi coupling

ClR1 Pd /Ligand +

Direct C–H functionalization of heteroaromatics for atom economy

Stabilizing polydentate ligands may help to this objective

that is not achieved under ligand-free conditions ?

8

9

Heteroaromatics functionalization as waste valorization

Furan derivatives from agriculture wastes as starting materials ?

10

Convergent synthesis towards high-value fine chemicals ?

High value convergent synthesis

N

CONHPh

FCO2H

OH OH

Atorvastatin cholesterol regulator

=> 12 billion US$ sales in 2008

Dantrolen : Muscle relaxant Amiphenazole

respiratory stimulant

11

A 2nd generation of ferrocenylphosphines for C–H/C–Cl cross-coupling

S. Mom, J.-C. Hierso et al. Inorg. Chem. , 2011, 50, 11592. Sophal Mom (PhD ANR)

12 D. Roy, S. Mom, H. Doucet, J.-C. Hierso Angew. Chem. Int. Ed., 2010, 49, 6650.

X

CN

X = O (83%)X = S (90%)

X

CN

X = O (85%)X = S (17%)

X

C N

X = O (87%)X = S (52%)

S

CN

O

O

79 %

SC

C

52%

N

NX

O

X = O (72%)X = S (73%)

O

O

O60%

CNX

X = O (84%)X = S (90%)

O

X

O2N

X = O (74%)X = S (80%)X

F3C

X = O (73%)X = S (81%)

N

S

92%

CNN

S

83%O

N

S

62%O

N

77%O

O

N

C

90%

NO

N

63%

O

O

N

63%C N

ON

50% O

O

Direct arylation in -C2 (or C5) from activated chlorides

Functionalized thiophenes and furans

Functionalized pyrroles and thiazoles

D. Roy (PhD ANR)

13 D. Roy, S. Mom, J.-C. Hierso, H. Doucet et al. Chem.-Eur. J., 2011, 17, 6453.

O

O

O

72%

O

O 71%

N

S

94%

N O 60%S

CN92% O

O

O

68%

O

O

O

CN

93%

SCN

CN 93%

N

CN

O52%

SCN

90%

O

OH

86%

O

EtO

OEt

O

68%

Naphtalenes

Anthracenes

Biphenyls Ortho and di-ortho-functionalized arenes

Direct arylation in -C2 (or C5) from congested bromides

D. Roy, D. Lucas, J.-C. Hierso, H. Doucet et al. ACS Catalysis, 2012, 1033.

Isoxazoles

Pyrazoles

Indoles

Benzofurans

Steric effects and flexibility are

dominant over electronic effects

(ē donation is equivalent to PPh3)

Direct arylation in -C3 (ou C4) from activated chlorides

14

15

C–O coupling of substituted phenols with heteroaryl chlorides

M. Platon, J.-C. Hierso et al. Adv. Synth. Catal. 2011, 353, 3403-3414.

98%

NO

99%

NO

NC

88%

NO OMe

95%N

NO

90%N

NO

O

61%N

S

87%

NO

iPr75%

NO

iPr

55%

NO

iPr

iPr98%

NO

NC

MeO

60%

NO

NH2

84%

NO

CEtO

O

98%

NO

NCF

90%

NO

92%

NO

OMe

NC 80%

NO

CEtO O 21%

NO

CEtO O

N

N

O

90%

Mélanie Platon (PhD)

tBu

Ph2P

PPh2

PPh2

tBu

PPh2

Fe

Pd

Br

Br

Fe

tBu

Ph2P

PPh2

PPh2

tBu

PPh2

Pd0

Electrochemicalreduction

Fe

tBu

Ph2P

PPh2

PPh2

tBu

PPh2

Pd0

Stabilization f romthe involvement

of the third phosphorus

Unstable speciesdetected in NMR

(low lif e-time)

35 ppm

23 ppm

34 ppm

- 20 ppm

tBu

Ph2P

PPh2

PPh2

tBu

PPh2

Fe

Pd

I

I

Oxidativeaddition

t1/2 = 130 ms

t1/2 = 30 s for [Pd0(PPh3)4] 200 times slower

t1/2 = 80 ms for “Pd0(PPh3)2” Stability gain x1,5

D. Evrard, D. Lucas, J.-C. Hierso, et al. Organometallics, 2008, 27, 2643.

Influence of polyphosphines on the reactivity of Pd(0)

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Oxydative addition (OA) of aryl halides

V. Zinovyeva, D. Lucas, J.-C. Hierso et al. Chem. Eur. J. , 2011, 17, 9901. 17

Influence of polyphosphines on the selectivity of OA

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Influence of polyphosphines on the reactivity of Pd(II)

Reductive elimination (RE) of heteroaromatic aryl ethers

M. Platon, M. Saeys, J.-C. Hierso et al. Adv. Synth. Catal. 2011, 353, 3403.

For the lowest energy pathway RE is 400-fold faster at 115 °C

(effective activation barrier is 19 kJ/mol lower than that for RE.TS1 pathway).

Iso.TS1-2

Iso.TS2-3

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Copper-phosphine chemistry for economic and fundamental concerns

Copper reserves : 5.5x108 t 25 years to 60 years left Price : 4-7 €/Kg

Palladium reserves : 8.0x104 t 300 years left Price : 6000 – 40000 €/Kg

• Copper catalysis (Ullmann, Click, etc.) is dominated by complexes having nitrogen an oxygen-containing ligands .

Phosphine are almost absent (HSAB theory): what about polyphosphines ?

• Fine mechanisms are poorly-known compared to palladium catalysis ( CuI/CuIII ??) could we get some help from 31P NMR ?

CuI/k3-tetra- and triphos

First Cu-polyphosphine adducts for Sonogashira coupling

M. Beaupérin, A. Job, J.-C. Hierso et al. Organometallics 2010, 29, 2815. 20

(1) concurrent palladium catalytic cycle for alkyne dimerization

I. J. S. Fairlamb et al., J. Org. Chem. 2005, 70, 703.

CuI-adducts only does not achieve Sonogashira reaction… …but may be are an inventive way to prevent diyne formation* !

(2) concurrent copper-dimers promoting alkyne dimerization

F. Diederich et al. Angew. Chem., Int. Ed. 2000, 39, 2632.

* Diyne formation promoted by O2 is the major concurrent reaction of alkynes arylation 21

A simple copper-diolefin for versatile arylation of pyrazole

V. Rampazzi, P. Le Gendre, J.-C. Hierso et al. ChemCatChem , 2012, DOI10.1002/cctc.201200368

[CuIPPh2(Cyhd)]4

(Cyclohepta-3,5-dienyl)diphenylphosphine

Molecularly-defined cubane precatalyst

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M. Taillefer et al., Angew. Chem. Int. Ed. 2009, 48, 333-336.

Arylation of nucleophiles with a butadienylphosphine

A large scope of (hetero)aromatic bromides coupled to pyrazoles

Pyridinyl

Pyrimidinyl

Furyl

Thienyl Thiazolyl

Aryl

The trap of aromatic chlorides: easy SNAr

V. Rampazzi, P. Le Gendre, J.-C. Hierso et al. ChemCatChem , 2012, DOI10.1002/cctc.201200368 23

Team ANR U. Dijon

J-C Hierso Dominique Lucas Philippe Meunier Régine Amardeil Charles Devillers

S. Mom Vero Zinovyeva

Special thanks and support

• Université de Bourgogne et Université de Rennes • CNRS – Institut de Chimie • ANR (Programme CP2D et Blanc - ANR Camelot) • RDR – GDR Chimie durable • Ministère des Affaires Etrangères et Programme Hubert Curien • Département de valorisation de l’IC-CNRS

Team ANR U. Rennes

Henri Doucet J. Roger D. Roy

Institut Universitaire de France Conseil régional de

Bourgogne 24

ANR Camelot (2009-2012): Main bibliography

S. Mom, J.-C. Hierso et al. Inorg. Chem., 2011, 50, 11592.

D. Roy, S. Mom, H. Doucet, J.-C. Hierso Angew. Chem. Int. Ed., 2010, 49, 6650.

D. Roy, S. Mom, J.-C. Hierso, H. Doucet et al. Chem. Eur. J., 2011, 17, 6453.

• Main topic : polyphosphines – C–H/C–Cl functionalization – palladium

• Second topic : phosphine ligands – copper catalysis

• Related topics : arylation reactions – catalysis in water and ionic liquids

D. Roy, S. Royer D. Lucas, J.-C. Hierso, H. Doucet et al. ACS Catalysis, 2012,1033.

V. Zinovyeva, D. Lucas, J.-C. Hierso et al. Chem. Eur. J., 2011, 17, 9901.

J. Roger, S. Mom, H. Doucet, J.-C Hierso ChemCatChem , 2010, 2, 296.

M. Platon, M. Saeys, J.-C. Hierso et al. Adv. Synth. Catal. 2011, 353, 3403.

S. Saleh, S. Mom, H. Doucet, J.-C Hierso et al. Synlett. 2011, 19, 2844.

V. Zinovyeva, D. Lucas, J.-C. Hierso et al. Adv. Funct. Mater. 2011, 21, 1064.

V. Rampazzi, P. Le Gendre, J.-C Hierso et al. ChemCatChem. 2012, DOI10.1002/cctc.201200368

M. Beaupérin, A. Job, J.-C. Hierso et al. Organometallics 2010, 29, 2815.

M. Platon, J.-C. Hierso et al. Chem. Soc. Rev. 2012, 41, 3929. 25

Commercially available

http://www.strem.com/catalog/ligands.php HiersoPHOS-1 à 5

HiersoPHOS-1

3 4

2

5

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