well-defined copper(i) complexes: useful tools in organic synthesis dr. silvia díez-gonzález...

Well-Defined Copper(I) Complexes:Useful Tools in Organic Synthesis

Dr. Silvia Díez-GonzálezDepartment of Chemistry, Imperial College London

03-Feb-2010

Overview: NHC–Metal Complexes

N NR R

[M]

Hydrosilylation[3+2] Cycloaddition

CycloisomerizationAlkyne Activation

TelomerizationCross-CouplingHydroarylationHydrothiolation

Aryl Amination

NiPd

Cu

Au Olefin MetathesisHydrogenation

Ru

IrC-H Activation

Pt

Rh

N-Heterocyclic Carbene Ligands (NHC)

stabilized and localized lone pairexcellent -donor ligand

tunable appending

groups

saturated/unsaturatedsubstituted/unsubstituted

tunable at will

Reviews: (a) Special Issue Chem. Rev. 2009, 109, 3209–3884. (b) Angew. Chem., Int. Ed. 2008, 47, 3122–3172.

NNR R -donor and -acceptor(stabilization of the carbene)

Strong NHC-metal bond, low degradation, low toxicity

N-Heterocyclic Carbene Ligands

N N RR

N N

IAd

N NN N

IMesIPr

N N

ICy

N N

SIPr

N N

SIMes

N N

ItBu

Synthesis of NHCs: IPr as a Showcase

Flexible and scalable synthesis

NH2

O

HH

ONN2

MeOH

liquid liquid DAB-Pr (solid)

+RT

O

HH

HClN N

H

Cl

IPr•HCl

baseN N

IPr

Large Scale Synthesis: 3 Kg of IPr•HCl

QuickTime™ and aTIFF (LZW) decompressor

are needed to see this picture.

Large Scale Synthesis: 3 Kg of IPr•HCl

DAB-Pr

IPrHCl





NN

N N

H

Cl

[(NHC)Cu] Complexes in Catalysis

Allylic Alkylation

N-Arylation

ATRC

Aziridination

Diboration

Conjugate Addition

Hydroamination

HydroalkoxylationReviews: (a) Díez-González, S.; Nolan, S. P. Aldrichimica Acta 2008, 41, 43–51. (b) Díez-González, S.; Nolan, S. P. Synlett 2007, 2158–2167.

N

N

R

R

Cu

R1 R2

O

R1 R2R1 R2

OR

R6

R7

R7CHR6 +

NN

NR3

+ R4 R5

N NN

R5R4

R3

CATALYSTS PREPARATION

Synthesis of [(NHC)CuX] Complexes

CuX, Base

Solvent, RT N

N

R

R

CuXN

N

R

R

H

Y

NaOt-Bu, THF or KOMe, Toluene

70–93%

THF, RT

N

N

R

R

CuX

71–90%

N N

ICy

N N

ItBu

N NN N

SIPrIPr

N N

IMes

N N

SIMes

N N

IAd

19 Highly Stable Complexes

X= Cl, Br or I

[(NHC)CuX]: Crystal Structures

C1

Cl

Cu

N2N1 N1

C1

Cu

Cl

N2

Cu–C1 = 1.956 ÅC1–Cu–Cl = 180.0°

Cu–C1 = 1.925 ÅC1–Cu–Cl = 171.6°

[(IPr)CuCl] [(ICy)CuCl]

[(NHC)CuX]: Crystal Structures (II)

N(1)

N(2)

Cu(1)C(1)I(1)

I(1')

Cu(1')

N(3)

N(5)

N(6)

C(1)

N(2)

N(4)

C(2)

Cu(2)

C(3)

Cu(3)

N(1)

Cu(1)

I(1)

I(2)

I(3)

Cu(1)–C(1) = 1.946 ÅC(1)–Cu(1)–I(1) = 137.9°

[(IAd)CuI] [(ICy)CuI]

Cu–C =1.927/1.973ÅCu(1)–Cu(2) = 2.453 Å

Undesired Reaction: New Family of Complexes

CuX, base

Solvent, RT N

N

R

R

CuXN

N

R

R

H

Y

+ ?

60% – 93% 0% – 40%

First [(NHC)Cu] known in the literature:

Arduengo, A. J., III; Rasika Dias, H. V.; Calabrese, J. C.; Davidson, F. Organometallics 1993, 12, 3405-3409.

N

N

Mes

Mes

CuN

N

Mes

Mes

OTf

Synthesis of [(NHC)2Cu]X Complexes

[Cu(NCCH3)4]X +THF, RT

[(NHC)2Cu]XNHCįHBF4

2 equiv

NaOt-Bu(2 Š 2.6 equiv)

63 Š 100%

N N

ICy

N N

ItBu

N NN N

SIPrIPr

N N

IMes

N N

SIMes

N N

IAd

14 Highly Stable Complexes

X= PF6 or BF4

[(NHC)2Cu]X: Crystal Structures

Cu

N1 C1N2

F1

B

Cu

PF1

N2

N1

C1

[(IPr)2Cu]BF4 [(IAd)2Cu]PF6

Cu–C(1) = 1.938 ÅN1–C1–Cu–C1’–N1’ = 49.9°

Cu–C1 = 1.933 ÅN1–C1–Cu–C1’–N1’ = 86.8°

Catalytic Studies

HYDROSILYLATION REACTIONS

Previous work with [(NHC)CuX] Complexes

,-Unsaturated Ketones and Esters

Simple Ketones

Jurkauskas, V.; Sadighi, J.; Buchwald, S. L. Org. Lett. 2003, 5, 2417-2420.

Kaur, H.; Zinn, F. K.; Stevens, E. D.; Nolan, S. P. Organometallics 2004, 23, 1157-1160.

O

R1

R2n

[(IPr)CuCl], NaOt-Bu

PMHS, toluene, RT

O

R1

R2

[(IPr)CuCl], NaOt-Bu

PMHS, t-BuOH, toluene, RTPh

R1

OEt

O

R2

Ph

R1

OEt

O

R2

n

R1 R2

O

R1 R2

OSiEt3[(IPr)CuCl], NaOt-Bu

Et3SiH, toluene, RT

N

NCuCl

i-Pr

i-Pr

i-Pr

i-Pr

[(IPr)CuCl]

Hydrosilylation of Challenging Substrates

Hindered Ketones

Díez-González, S.; Kaur, H. Zinn, F. K.; Stevens, E. D.; Nolan, S. P. J. Org. Chem. 2005, 70, 4784–4796.

N

NCuCl

[(ICy)CuCl]

Functionalized Ketones

OSiEt3

OSiEt3

OSiEt3

OSiEt3

3.5 h, 93%60 : 40

4 h, 91%

3 h, 96%

0.5 h, 97%

N

OSiEt3

Br

OSiEt3 CF3 OSiEt3

OSiEt3

MeO

1 h, 93%

1 h, 99% 2 h, 88%

0.5 h, 94%

R1 R2

O

R1 R2

OSiEt3[(ICy)CuCl] (3 mol %)

NaOt-Bu (12 mol %), Et3SiH (3 equiv)Toluene, 80°C

Hydrosilylation of Challenging Substrates (II)

Díez-González et al. J. Org. Chem. 2005, 70, 4784–4796.

Heteroaromatic Ketones

N

OSiEt3 OSiEt3 OSiEt3

OSiEt3 OSiEt3

S

N

N

SO

0.5 h, 94% 0.5 h, 94% 0.5 h, 97%

4.5 h, 95% 7 h, 93%

N

NCuCl

[(SIMes)CuCl]

Ar

OSiEt3[(SIMes)CuCl] (3 mol %)

NaOt-Bu (3 mol %), Et3SiH (2 equiv)Toluene, 80°C

Ar

O

Proposed Mechanism

Díez-González et al. J. Org. Chem. 2005, 70, 4784–4796.

[(NHC)CuCl] + NaCl

R3SiH

[(NHC)CuH]

R3SiH

R1 R2

O

R1

O

H

Cu(NHC)

R1

OSiR3

R2

R1 R2

O

R2

(NHC)HCu

R2

O(NHC)Cu

H

+

R3Si Ot-Bu

R1

NaOt-Bu[(NHC)CuOt-Bu]

[(NHC)2Cu]X: Hydrosilylation of Simple Ketones

[(IPr)2Cu]BF4 vs [(IPr)CuCl]

Díez-González, S.; Scott, N. M.; Nolan, S. P. Organometallics 2006, 25, 2355–2358.[(IPr)CuCl]: Kaur et al. Organometallics 2004, 23, 1157–1160.

[(IPr)CuCl] (3 mol%), NaOt-Bu (12 mol%), Et3SiH (3 equiv), toluene, RT

3 h, 93%2 h, 93% 4 h, 88% 5 h, 86% 1 h, 97%

0.5 h, 98% 1 h, 96% 0.33 h, 99% 4 h, 94% 0.33 h, 98%

OSiEt3

OSiEt3

OSiEt3

7

OSiEt3

OSiEt3

N N

IPrR1 R2

O

R1 R2

OSiEt3

[(IPr)2Cu]BF4 (3 mol %)NaOt-Bu (12 mol %)

Et3SiH (2 EQUIV), THF, RT

[(NHC)2Cu]X: Hydrosilylation of Aldehydes

Díez-González et al. Organometallics 2006, 25, 2355–2358.

N N

IPr

Also an ester:

OSiEt3 OSiEt3 OSiEt3

Cl

OSiEt3

MeO

OSiEt3 OSiEt3

20 min, 92% 25 min, 94% 15 min, 91%

15 min, 89% 40 min, 70% 45 min, 71%

O

OEt

OSiEt3

6 h, 55°C, 69%

[(IPr)2Cu]BF4 (3 mol %)

NaOt-Bu (12 mol %), Et3SiH (2 equiv)THF, RT

R1 H

O

R1 OSiEt3

[(NHC)2Cu]X: Hydrosilylation of Hindered Ketones

[(ICy)2Cu]BF4 vs [(ICy)CuCl]

Díez-González et al. Chem.–Eur. J. 2008, 14, 158–168.[(ICy)CuCl]: Díez-González et al. J. Org. Chem. 2005, 70, 4784–4796.

[(ICy)CuCl] (3 mol %), NaOt-Bu (12 mol %), Et3SiH (3 equiv), toluene, 80°C

0.5 h, 99% 1.5 h, 97% 0.25 h, 99% 0.6 h, 96%

[(ICy)CuCl] (3 mol %), NaOt-Bu (12 mol %), Et3SiH (2 equiv), toluene, 55ºC

1.5 h, 50%

1.5 h, 98% 5 h, 96% 0.5 h, 95% 2.5 h, 94%

N N

ICy

OSiEt3OSiEt3 OSiEt3OSiEt3

R1 R2

O

R1 R2

OSiEt3

[(ICy)2Cu]BF4 (3 mol %)NaOt-Bu (12 mol %)

Et3SiH (2 EQUIV), THF, 55C

Díez-González, et al. Chem.–Eur. J. 2008, 14, 158–168.

[(IPr)2Cu]BF4

CD3CN

py-d5

70 - 100°Cup to 5 days

+ PPh3

CD3CN or Tol-d8

70 – 100°C, 24 h

+ PCy3

CD3CN or Tol-d8

70 – 100°C, 24 h

[(IPr)2Cu]BF4

[(IPr)2Cu]BF4

Mechanistic Studies: Decomposition and Exchange Rates

N N

IPr

Mechanistic Studies: Active Species

N N

IPr

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8

time (h)

GC

con

v. (

%)

3 mol% IPr

6 mol% IPr

9 mol% IPr


Mono-NHC species as “true” catalyst

O

OSiEt3

[Cu(CH3CN)4]BF4 (3 mol %)IPr (X mol %)NaOt-Bu (12 mol %)Et3SiH (2 equiv), THF, RT

Mechanistic Studies: Role of the Base

N N

IPr


Base as a pre-catalyst activator

O[Cu] (3 mol %), Et3SiH (5 equiv)

NO BASE

THF, T

OSiEt3

[Cu] T (°C) time (h) GC conv. (%)

60 24 0

[Cu(CH3CN)4]BF4 + IPr 60 48 96

[Cu(CH3CN)4]BF4 + IPr 48 0

60 24 0

RT

[Cu(CH3CN)4]BF4

[(IPr)2Cu]BF4

Postulated Mechanism

Díez-González, et al. Chem.–Eur. J. 2008, 14, 158–168.Díez-González, et al. J. Org. Chem. 2005, 70, 4784–4796.

[(NHC)2Cu]X+ NHCTHF

NaOt-Bu[(NHC)CuX] + NaX

R3SiH

[(NHC)CuH]

R3SiH

R1 R2

O

R1

O

H

Cu(NHC)

R1

OSiR3

R2

R1 R2

O

R2

(NHC)HCu

R2

O(NHC)Cu

H

+

R3Si Ot-Bu

R1

NaOt-Bu[(NHC)CuOt-Bu]

Hydrosilylation Reactions: The Director’s Cut

Kaur, H.; Zinn, F. K.; Stevens, E. D.; Nolan, S. P. Organometallics 2004, 23, 1157–1160.

Initial Screening: Azolium Salts

O OSiEt3NHCHX (3 mol %), CuCl (3 mol %)NaOt-Bu (20 mol %)

Et3SiH (5 equiv), toluene, RT

IPr·HCl 2 h, 80%

IPr·HBF4 2 h, 99%

SIMes·HCl 7 h, 95%

SIMes·HBF4 8 h, 37%

ItBu·HBF4 8 h, 25%

N N

IPr

N N

SIMes

N N

ItBu

2 h, 99%

-

[(IPr)CuCl]

[(SIMes)CuCl] 1 h, 99%

[(ItBu)CuCl] 8 h, 99%

[(NHC)CuCl] (3 mol %), NaOt-Bu (12 mol %), Et3SiH (3 equiv), toluene, RT

Díez-González, S.; Escudero-Adán, E.; Benet-Buchholz, J.; Stevens, E. D.; Slawin, A. M. Z.; Nolan, S.P., submitted.





IPr·HCl 2 h, 80%

IPr·HBF4 2 h, 99%

SIMes·HCl 7 h, 95%


ItBu·HBF4 8 h, 25%

2 h, 99%

-

[(IPr)CuCl]





N N

IPr

Formation of [(IPr)2Cu]X(~ 10 %)

0.5 h, 99%[(IPr)2Cu]BF4

[(NHC)2Cu]X (3 mol %), NaOt-Bu (12 mol %), Et3SiH (2 equiv), THF, RT






IPr·HCl 2 h, 80%

IPr·HBF4 2 h, 99%

SIMes·HCl 7 h, 95%


ItBu·HBF4 8 h, 25%

2 h, 99%

-

[(IPr)CuCl]





N N

SIMes

~ 70% [(SIMes)2Cu]X

[(NHC)2Cu]X (3 mol %), NaOt-Bu (12 mol %), Et3SiH (2 equiv), THF, RT

[(SIMes)2Cu]BF4 24 h, 52%







IPr·HCl 2 h, 80%

IPr·HBF4 2 h, 99%

SIMes·HCl 7 h, 95%


ItBu·HBF4 8 h, 25%

2 h, 99%

-

[(IPr)CuCl]






Sluggish formation of the complex

N N

ItBu

Compared to [(IPr)CuCl]Compared to [(ICy)CuCl], reactions at 80ºC


Hydrosilylation Reactions: [(SIMes)CuCl]

N N

SIMes

3 h, 95%

0.25 h, 96%3 h, 83%

0.5 h, 93%1 h, 95%

0.5 h, 95%0.25 h, 99%

0.5 h, 98%1.5 h, 97%

1 h, 91%

OSiEt3 OSiEt3 OSiEt3 OSiEt3 Cl OSiEt3

R1 R2

O

R1 R2

OSiEt3

[(SIMes)CuCl] (3 mol %)NaOt-Bu (3 mol %)

Et3SiH (1.2 equiv), toluene, RT

Excellent activity under smoother conditions

Catalytic Studies

[3+2] CYCLOADDITION REACTIONS

CLICK CHEMISTRY

Click Chemistry

Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004–2021.

Assembly processes inspired by Nature

- Modular reactions under simple reaction conditions- Straightforward isolation (no chromatography!) for very high yields

Huisgen [3+2] Cycloaddition

Huisgen, R. Pure Appl. Chem. 1989, 61, 613–628.

N NNR2R1 +

NN

N

R1

R2+

NN

N R2

R1

[Cu]: (a) Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057–3064. (b) Rostovtev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2596–2599.

CuI

[(NHC)CuX] NMR

Conversion [(NHC)CuX] Isolated Yield

[(IPr)CuCl] 18% [(IMes)CuCl] 65%

[(IPr)CuBr] 18% [(IMes)CuBr] 94% (14 h)

[(IPr)CuI] 20% [(SIMes)CuCl] 93%

[(SIPr)CuCl] 9% [(SIMes)CuBr] 95% (9 h)

[(ICy)CuCl] 75% [(IAd)CuCl] 80%

N N

N N

SIPr

IPr

N N

ICy

N N

IMes

N N

SIMes

N N

IAd

N3Ph N

NN

Ph

Ph[(NHC)CuX] (5 mol %)

Water/tert-BuOH (3 mL)18 h, RT

+

Díez-González, S.; Correa, A.; Cavallo, L.; Nolan, S. P. Chem.–Eur. J. 2006, 12, 7558–7564.

[(NHC)CuX] Screening

Scope of the Reaction

R2N

NN

R2

R1[(SIMes)CuBr](0.8 mol %)+N3R1

Díez-González et al. Chem.–Eur. J. 2006, 12, 7558–7564.

NN

N

Bu

3.5 h, 94%

NN

N

2 h, 91%

O

OEt

Ph

Ph

NN

N

1.5 h, 93%

O2N

NN

N

Ph

30 min, 93%

NC

NN

N

30 min, 88%

NCOH

NN

N

SiMe3

45 min, 98%*

Ph

NN

NHept

OMe

15 min, 93%

NN

NHept

20 min, 89%

F

NN

NHept

5 h, 95%*

2 h, 90%

NN

N

Ph

HO 3

NN

NHept

20 min, 92%

O

OEt

NN

N

Ph

45 min, 94%

Ph NN

N

4 h, 94%*

Ph

OH

NN

NPh

1 h, 94%*

OH

NN

N

Ph

Ph

1.5 h, 86%

NN

N

45 min, 98%

O

O

OMe

[(SIMes)CuBr] vs [(IAd)CuI] for Click Chemistry

R2 NN

N

R2

R1[(NHC)CuX](0.8 mol %)+N3R1

Neat, RT

N

NCuBr

[(SIMes)CuBr]


NN

N

Bu

20 h, 87%

1.5 h, 95%

PhNN

N

SiMe3

18 h, 20%

11 h, 95%

Ph

NN

NHept

18 h, 80%

1 h, 96%

NN

N

18 h, 76%

20 min, 92%

Ph

OH

NN

N

4 h, 0%

4 h, 93%

O

O

OEt

O

N

NCuI

[(IAd)CuI]

Further Applications of [(NHC)CuX] as Click Catalysts

(a) Broggi, J.; Díez-González, S.; Petersen, J. L.; Berteina-Raboin, S.; Nolan, S. P.; Agrofoglio, L. A. Synthesis 2008, 141–148. (b) Broggi, J.; Joubert, N.; Díez-González, S.; Berteina-Raboin, S.; Zevaco, T.; Nolan, S. P.; Agrofoglio. L. A. Tetrahedron 2009, 65, 1162–1170.

Carbanucleosides as anti-pox agents

N

OH

NN

R

HO

HO

Porphyrine Functionalisation:

Séverac, M.; Le Pleux, L.; Scarpaci, A.; Blart, E.; Odobel, F. Tetrahedron Lett. 2007, 48, 6518–6522.

Chelators for anti-cancer drugs

H2NPt

N NN

Cl Cl

Maisonial, A.; Serafin, P.; Traïkia, M.; Debiton, E.; Théry, V.; Aitken, D. J.; Lemoine, P.; Viossat, B.; Gautier, A. Eur. J. Inorg. Chem. 2008, 298–305..

NAr N

N N

Ar Ar

N

Zn

NN R

Latent Click Catalyst

Díez-González, S.; Stevens, E. D.; Nolan, S. P. Chem. Commun. 2008, 4747–4749.

WaterN

NN

R1

R2

R2[(SIPr)CuCl]

DMSORT, 1 week

NO REACTION

R1 N3

[(SIPr)CuCl]

DMSO/Water60¼C, 0.5Š16 h

83Š98%

[(SIPr)CuCl]

N

NCuCl

NN

N

16 h, 98%16 h, 92%

O2N

NN

N

16 h, 78%

NCOH

NN

N

3 h, 97%2h, 92%

Ph

OHN

NNHept

0.6 h, 94%0.5 h, 91%

F

NN

N

2 h, 93%

O

O

OMe

NN

N

Bu

Hept

1 h, 83%0.5 h, 97%

In Situ Generated Azides


Water/t-BuOH, 75 - 125°C MW 10 – 15 min

Appukkuttan et al. Org. Lett. 2004, 6, 4223–4225

Previously reported conditions:

NN

NHept

0.5 h, 92%c

F

NN

NMe

2 h, 90%d

a From benzyl chloride; b From benzyl chloride, T = 70°C; c Reaction at 45°C; d From MeI

NN

N

Ph

1 h, 92%5 h, 93%a

0.3 h, 94%b

NN

N

Ph

1.5 h, 98%

O2N

R2N

NN

R2

R1NaN3 (1.05 equiv)[(SIMes)CuBr] (5 mol %)

+R1 BrWater, RT

Accepted Reaction Mechanism

Himo, F.; Lovell, T.; Hilgraf, R.; Rostovtsev, V. V.; Noodleman, L.; Sharpless, K. B.; Fokin, V. V.J. Am. Chem. Soc. 2004, 127, 210–216.

[Cu]

R2

R2[Cu]

R1 NN N

R2[Cu]

N R1NN

[Cu] •

NNNR1

R2

NN

NR1

[Cu] R2

NN

NR1

R2

Internal alkynes would not react under these

conditions…

Internal Alkynes

Díez-González et al. Chem.–Eur. J. 2006, 12, 7558–7564.For another example, see: Candelon, N.; Lastécouères, D.; Diallo, A. K.; Ruiz Aranzaes,

J.; Astruc, D.; Vincent, J.-M. Chem. Commun. 2008, 741–743.

EtEtN

NN

EtEt

+70°C, 48 h

N3

R = H 80%

R R[(SIMes)CuBr]

(5 mol %)

R = NO2 59%

Copper AND Ligand Effect:

No copper <5%

CuBr (5 mol %) 34%

Mechanistic implications…

DFT Calculations: Novel Activation of Alkynes

Activation towards cycloaddition via -binding unfavoured

Himo et al. J. Am. Chem. Soc. 2004, 127, 210–216.

R2

R1

N N N

R2

R1

N N N

[Cu]

Activation barrier: 25.7 kcal/mol 27.8 kcal/mol


The NHC facilitates the -Cu-alkyne binding and permits the cycloaddition

Cu

-17.6 kcal/mol -41.0 kcal/mol Binding energy

Cu

SIMes

NCMeMeCN

Distinct Mechanisms Depending on the Alkyne Nature


[(NHC)Cu]

R2

R1N

N N

R2

Cu

R2R2

NHC

NN

NR1

R2 R2

R2R2

Cu

NHC

Cu

NHC

R2

R2(NHC)Cu

R1N

N N

NN

NR1

R2

NN

NR1

R2R2

[(NHC)2Cu]X as Click Catalysts: Very Low [Cu] Loadings

Díez-González, S.; Nolan, S. P. Angew. Chem., Int. Ed. 2008, 47, 8881–8884.

N N

ICy R2 NN

N

R2

R1[(ICy)2Cu]PF6(X mol %)

+N3R1

T

TONs up to 20 250; TOFs up to 5000 h-1

N NNPh N N

NPh

NMe2

NN

N

Ph

PhN N

NPh

N

N NNHept

PhCl3

75 ppm6 h, 91%

300 ppm40 h, 45%

200 ppm20 h, 72%

300 ppm43 h, 85%

50 ppm48 h, 80%

RT

50 ppm8 h, 89%

100 ppm18 h, 70%

100 ppm18 h, 70%

40°C

50°C40 ppm4 h, 81%

Proposed Mechanism for [(NHC)2Cu]X Catalysts

Díez-González, S. et al. Angew. Chem., Int. Ed. 2008, 47, 8881–8884.

[(ICy)2Cu]PF6

R2

R2[(ICy)Cu]

R1N

N N

R2[Cu]

N R1NN

[Cu]

NNNR1

R2

NN

NR1

[Cu] R2

NN

NR1

R2

ICyįHPF6

[(NHC)CuI] Complexes: CONCLUSIONS

[(NHC)CuX] & [(NHC)2Cu]X

• Practical preparation, high stability

• Active under smoother conditions

• Enhanced catalytic activity • Active at ppm levels

• KEY ROLE OF THE SECOND NHC

• Excellent catalysts for hydrosilylation and [3+2] cycloaddition reactions

[(NHC)CuX] [(NHC)2Cu]X

• Catalysts of choice for very challenging ketones

• Low catalyst loading (< 1 mol %) • Use of internal alkynes

• Latent catalyst

[(NHC)CuI] Complexes: CONCLUSIONS

Preparation of a library of well-defined complexes

• Organometallic interest: - Synthetic procedures- Coordination chemistry

• Better chances of finding the optimal catalysts

• Improved control of the species present in the reaction media- Catalytic performance- Mechanistic implications

ACKNOWLEDGEMENTS

QuickTime™ et undécompresseur TIFF (non compressé)

sont requis pour visionner cette image.

• Crystallography: Prof. Edwin D. Stevens & Dr. Natalie M. Scott (UNO)Prof. Jeffrey Petersen (West Virginia)Eduardo Escudero, Dr. Jordi Benet (ICIQ)Prof. Alex M. Z. Slawin (St. Andrews)

• DFT Calculations: Dr. Andrea Correa & Prof. Luigi Cavallo (Salerno)

• Hosting: Prof. Deryn Fogg (Ottawa)

• Collaborators: Prof. Hélène Lebel (Montreal)Prof. Arnaud Gautier (Blaise-Pascal – Clermont)Prof. Olivier Riant (Louvain)

well-defined copper(i) complexes: useful tools in organic synthesis dr. silvia díez-gonzález...

Documents

iprhcl slide

iprcuclicycucl slide

ketones dezgonzlez

rt dezgonzlez

base dezgonzlez

b dezgonzlez

scalable synthesis slide

vs icycucl dezgonzlez