cooperative dual catalysis: combining transition metal catalysis

Cooperative dual catalysis:

Combining transition metal catalysis and

organocatalysis in organic synthesis

Amila A Dissanayake

Michigan State University

2010.02.17

� Introduction to Cooperative dual catalysis

� Cooperative dual catalysis modes

� Combining Transition Metal catalysis and Organocatalysis

� Combining Transition Metal complex and Aminocatalysis

� Combining Transition Metal complex and Bronsted acids

OUTLINE

� Combining Transition Metal complex and Bronsted acids

� Chelation assisted metal organic cooperative catalysis

� Hydrogen-bond assisted metal organic cooperative catalysis

� Summary

� Acknowledgments

Cooperative Dual Catalysis

� Two different catalytic systems functioning cooperatively

� Enables unprecedented transformations not currently possibly by

use of each catalytic systems alone

Jacobson, E. N.; Danjo, H.; Sammis, G. M. J. Am. Chem. Soc. 2004, 126. 9928-9929.

Disadvantages

� Catalysis compatibility

1. Anodic Oxidation and Organocatalysis


2. Combination of Organocatalysis and Biocatalysis

3. Combining Photoredox catalysis and Organocatalysis

4. Combining Transition Metal catalysis and Organocatalysis


Jensen, K. L.; Franke, T. P.; Jorgensen, K. A. Angew. Chem. Int. Ed. 2010, 49, 129-133.

Proposed mechanism for the Electrochemical/Organocatalytic sequence

O

NHTs NTs

NOTMS

Ph

Ph

R

OH

N OTMS

Ph

Ph

R

H2O

Anodicoxidation


R OH O

NH OTMS

Ph

PhN OTMS

Ph

Ph

O

NTs

H

RH2O

O

O

NHTs

H

R

O

OH

NHTs

R

NHTs

O

OH

R

Organocatalysis

2. Combination of Organocatalysis and Biocatalysis

asymmetricbiocatalysis

OH OH

R'R

Baer, K.; Burda, E.; Hummel, W.; Berkessel, A.; Groger, H. Angew. Chem. Int. Ed. 2009, 48, 9355-9358.

Biocatalysis:

formation of the

2nd stereogenic

center

Combination of Organocatalysis and Biocatalysis

O

Cl

+

NH

NH

OH

O

Ph PhOH O

Cl

(S,S)

OH OH

Cl

OH OH

Cl

(1R,3S)d.r 1:11> 99% ee

(1R,3R)d.r 11:1> 99% ee

(S)-ADH

NAD+

2-PrOH

(R)-ADH

NADP+

2-PrOH

Baer, K.; Burda, E.; Hummel, W.; Berkessel, A.; Groger, H. Angew. Chem. Int. Ed. 2009, 48, 9355-9358.

O

NH

NH

OH

O

Ph Ph

(R,R)

OH O

Cl

Organocatalysis

OH OH

Cl

OH OH

Cl

(1S,3S)d.r 11:1> 99% ee

(1S,3R)d.r 1:10> 99% ee

(S)-ADH

NAD+

2-PrOH

(R)-ADH

NADP+

2-PrOH

Biocatalysis

3. Combining Photoredox catalysis and Organocatalysis

Enantioselective catalytic carbonyl α-alkylation

2

Nicewicz, D. A.; MacMillan, D. W. C. Science. 2008. 322. 77-80.

NH

N

O

Me

Me

tBu

Organocatlyst (20 mol%)

Ru

N N

NNN

N

2Cl

Photoredox catalyst(0.5 mol%)

Transition metal catalyzed reactions in organic synthesis

o Hydroformylation

o Multiple C-C bond formations

o Hydrocarboxylations

o Hydroesterifications

o Cross-coupling reactions

o Amidocarboxylation of aldehydes

Few Transition metal catalyzed reactions

Why transition metal catalyzed reactions?

o Chemoselectivity

o Regioselectivity

o Diastereoselectivity

o Enantioselectivity

M. Beller and C. Bolm, Transition Metals for Organic Synthesis: Building Blocks and Fine Chemicals, Wiley-VCH,

Weinheim, 2nd edn, 2004, vol. 1.

o Alkene and Alkyne Hydrocyanation

o Cyclopropanation

o Isomerization of olefins

o Alkene and alkyne metathesis

o Hydroamination

o Pauson-Khand reaction

o Conjugate addition reactions

o Enantioselectivity

o High yield

o Reproducibility

Organocatalysis

Use of small organic molecules to catalyze organic transformations through

unique activation modes.

Main advantages of organocatalysis

o Stable in air and water

o Available from biological materials

o Inexpensive and easy to prepare

o Simple to use

Asymmetric organocatalysis / enantioselective organocatalysis

MacMillan, D. W. C. Nature. 2008. 455, 304-308.

Hajos, Z. G.;Parrish, D. R. J. Org. Chem. 1974. 39(12). 1615-1621.

Asymmetric organocatalysis / enantioselective organocatalysis

Hajos-Parrish reaction (1970)

Substrate Catalyst Activation modes# of new

reactionsNew reaction variants

25

Intramolecular

α-alkylation

α-Amination

α-Halogenation

Generic modes of activation used in organocatalysis

Enamine catalysis

Hydrogen-bonding catalysis




30

Stecker reaction

Mannich reaction

Ketone cyanocilation

Reductive amination

Biginelli reaction

HN

N N

NO

S

R''R''

t-Bu

X

R R'

H H

Nu:

LUMO activation

Hydrogen-bonding catalysis



50

Conjugate amination

Conjugate oxygenation

Cyclopropanation

Ketone Diels-Alder

reaction

Mukaiyama-Michael

reaction


Iminium catalysis

N

N

O

t-BuPh

RNu:

LUMO activation



4

α-Allylation

α-Enolation

α-Vinylation

α-Heteroarylation

SOMO catalysis




2

Acyl-Pictet=Spengler

Reaction

Oxocarbenium

addition reaction


Counterion catalysis

C5H11nN

N N

NO

St-Bu

R'''

H HCl

X R''

R

R'

Nu:

LUMO activationLUMO activation


4. Combining transition metal catalysis and organocatalysis

� Combining transition metal complex and aminocatalysis

� Combining transition metal complex and Bronsted acids



Carbocyclization approachs

Combining transition metal complex and aminocatalysis

Binder, J. T.; Crone, B.; Haug, T. T.; Menz, H.; Kirsch, S. F. Org. Lett. 2008. 10. 1025–1028.

Entry Catalysis A (mol %) Catalysis B (mol %) ConditionsYield (%)

Direct carbocyclization of aldehydes with alkynes

Entry Catalysis A (mol %) Catalysis B (mol %) ConditionsYield (%)

X: Y: Z

1 120 °C, toluene, 24 h 100: 0: 0

2 [(Ph3PAu)3O]BF4 (10) 70 °C, CDCl3, 6 h 82: 0: 0

3 HN(i-Pr)2 (20) 70 °C, CDCl3, 6 h 100: 0: 0

4 [(Ph3PAu)3O]BF4 (10) HN(i-Pr)2 (20) 70 °C, CDCl3, 6 h 0: 0: 86

5 [(Ph3PAu)3O]BF4 (10) HN(i-Pr)(c-Hex) (20) 70 °C, CDCl3, 6 h 0: 0: 84

6 [(Ph3PAu)3O]BF4 (10) H2N(i-Pr) (20) 70 °C, CDCl3, 6 h 0: 0: 74


Proposed mechanism for carbocyclization of aldehydes with alkynes


Direct carbocyclization of aldehydes with alkynes


Carbocyclization of aldehydes with alkynes intramolecular approach

Zhao, G. L.; Ulah, F.; Zhang, Q.; Sun, J.; Lbrahem, I.;Cordova, A. Chem. Eur. J. 2010. 16. 1585-1591.

Jenson, K. L.; Frenke, P, T.; Arroniz, C.; Jorgensen, K. A. Chem. Eur. J. 2010. 16. 1750-1753.

Entry Metal salt Solvent Organocatalyst Time [h] Yield ee [%]


Zhao, G. L.; Ulah, F.; Zhang, Q.; Sun, J.; Lbrahem, I.;Cordova, A. Chem. Eur. J. 2010. 16. 1585-1591.

Entry Metal salt Solvent Organocatalyst Time [h] Yield ee [%]

1 [Pd(PPh3)]4 MeOH a 46 22 94

2 [Pd(PPh3)]4 CHCl3 a 88 45 94

3 [Pd(PPh3)]4 ClCH2CH2Cl a 88 42 98

4 [Pd(PPh3)]4 CH3CN a 40 80 98

5 [Pd(PPh3)]4 CH3CN b 66 0 0

6 [Pd(PPh3)]4 CH3CN c 72 26 <5

7 [Pd(PPh3)]4 CH3CN d 88 22 92

Entry R1 T [h] Yield [%] d.r ee [%]

1 16 59 7:1 95

2 15 60 12:1 86


Organocatalyst

NH

OTMS

Ph

Ph

a

Jenson, K. L.; Frenke, P, T.; Arroniz, C.; Jorgensen, K. A. Chem. Eur. J. 2010. 16. 1750-1753.

2 15 60 12:1 86

3 16 56 3:1 92

4 16 55 7:1 89

Me

� First example of highly enantioselective DYKAT (type IV) procedure.

(Dynamic Kinetic Asymmetric Transformation)

� Formation of all-carbon quaternary stereocenters with stereoselectivity.

Palladium-Catalyzed Asymmetric Allylic Alkylations

HN

OO

NH

PPh2 Ph2P

Tsuji-Trost reaction

Trost, B. M.; Radinov, R.; Grenzer, E. M. J. Am. Chem. Soc. 1997, 119, 7879-7882.

Bihelovic.; F. Matavic.; R. Vulovic.; B. Saicic,; R. N. Org. Lett. 2007. 9. 5063-5066.

Organocatalyzed cyclization of π-allylpalladium complexes

Reactant productYield

trans/cis

72%

11/1

63%

10/1

OHC

Br

Br

Organocatalyzed cyclization of π-allylpalladium complexes

80%

10/1

60%

7/1

95%

7/1

NTs

OHC

Bihelovic.; F, Matavic.; R. Vulovic.; B. Saicic,; R. N. Org. Lett. 2007. 9. 5063-5066

CHO

BnOOTBDMS

Proposed mechanism for Organocatalyzed cyclization of π-allylpalladium complex

OHC

OX

N

NH

[PdL2]

H2O

N[Pd]

NX

H2O

[PdL2]

Bihelovic.; F. Matavic.; R. Vulovic.; B. Saicic, R. N. Org. Lett. 2007. 9. 5063-5066

Allylic alkylation of enolizable ketones and aldehydes with allylic alcohols

Usui, I.; Schmidt, S.; Breit, B. Org. Lett. 2009. 11. 1453-1453.



Entry Organocatalyst Yield %

a L-1 50

b 2 0

c 3 0

d 4 20

e (DL)-1 89

Proposed Mechanism


O

PPh2 PPh2

Xantphos

L L=


Entry Ketone/Aldehyde Products Yield %

1 89

2 75

3 96

O

Ph


4 85

5 78

6 81

7 73

O

O O

O

Ph




� Combining transition metal complex and Bronsted acids� Combining transition metal complex and Bronsted acids



� Chiral Bronsted acids are important in asymmetric organocatalysis

� Activation of the electrophile through protonation to form chiral ion pair

� Led to development of enantioselective;

� Mannich and Mannich-Michael reaction

� Nazarov cyclization

� Imino−Azaenamine reaction

Enantioselective Bronsted acids in organic synthesis

� Imino−Azaenamine reaction

Rueping.; M. Antonchick.; P. A, Brinkmann, C. Angew. Chem. Int. Ed. 2007, 46,6903-6906.

Rueping.; M. Suniono.; E. Theissmann.; T. Kuenkel.; A. Bellar.; M. Org. Lett. 2007. 9. 1065.

Entry 1 Ar X 1 [mol %] e.r.

A 1a phenyl OH 10 57:14

Asymmetric alkynylation of imines


A 1a phenyl OH 10 57:14

B 1b 1-napthyl OH 10 55:45

C 1c 2-napthyl OH 10 54:46

D 1d 3,5-(CF3)2C6H3 OH 5 62:38

E 1e 9-phenanthryl OH 5 86:14

F 1e 9-phenanthryl OH 10 91:9

G 1f 9-phenanthryl NHTf 10 41:59

H 1g 9-anthracenyl NHTf 10 31:69

Entry MX MX [mol%] 1e [mol%] R e.r.


Entry MX MX [mol%] 1e [mol%] R e.r.

1 AgOAc 5 2 Et 76:24

2 AgOAc 5 5 Et 86:14

3 AgOAc 5 10 Et 91:9

4 AgOAc 5 20 Et 87:13

5 AgOAc 5 10 Me 94:6

6 AgNO3 5 10 Et 81:19

7 CuOAc 5 10 Et 92:8

8 Cu(OAc)2 5 10 Et 93:7




� Reaction catalyzed by a chiral metal complex in combination

with a chiral Bronsted acid catalysis

� Chiral silver-binol complexes results racemic mixtures

Asymmetric alkynylation of imines-Recent Discovery

Armas.; P, Tejedor.; D, Tellado, F. G. Angew. Chem. Int. Ed. 2009, 48,2-6.

Lu.; Y, Johnstene.; T. C, Arndtsen.; B. A. J. Am. Chem. Soc. 2009. 131. 11284-11285.

� Significant downfield shift anticipated by a H-bonding interaction

� Association constant consistent with weak interactions to form corresponding

Chiral H-bonding complex

� Kinetic studies;

Two different catalytic cycles

Asymmetric alkynylation of imines-Recent Discovery

Armas.; P. Tejedor.; D. Tellado, F. G. Angew. Chem. Int. Ed. 2009, 48,2-6.

Asymmetric reductive amination

AH

O

OPO

OH

R'

R'

R' =2,4,6-iPr3C6H2

=

Bronsted acid;

� Catalyzes the formation of the imine

Klussmann.; M. Angew. Chem. Int. Ed. 2009, 48, 7124-7125.

� Catalyzes the formation of the imine

� Serve as a chiral counterion to the iridium catalyst

� Serve as a chiral counterion to the iminium ion

Enantioselective three-component reactions

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

Entry Ar1 Ar3 yield (%) dr ee (%)

1 Ph m-CH3C6H4 95 >99/1 90

2 Ph Ph 83 >99/1 94

3 Ph o-CH3C6H4 95 >99/1 93

4 Ph p-BrC6H4 87 >99/1 92

5 p-MeOC6H4 Ph 98 >99/1 >99

6 p-MeOC6H4 p-BrC6H4 97 >99/1 95

Enantioselective α-allylation of α-branched aldehydes

Murahashi.; S, List.; B. Am. Chem. Soc. 2007. 129. 11336-11337.

First enantioselective α-allylation of α-branched aldehydes to create all-

carbon quaternary stereogenic center.

Proposed reaction mechanism for the enantioselective α-allylation of

α-branched aldehydes

Murahashi.; S, List.; B. Am. Chem. Soc. 2007. 129. 11336-11337.

Han.; Z. Y, Xiao.; H, Chen.; X. H, Gong.; L. Z. J. Am. Chem. Soc. 2009. 131. 9182-9183.

Consecutive intramolecular hydroamination/Asymmetric transfer hydrogenation

Enantioselective reductive coupling

Komanduri.; V, Krische.; M. J. J. Am. Chem. Soc. 2006. 128. 16448-16449.

Chelation assisted metal organic cooperative catalysis

Hydroacylation

[M]R H

CO

[M] CO

R H

Decarbonylation

+

Jun, C. H.; Lee, J. A.; Ahn, B. I.; Park, Y. J. Chem. Commun. 2008. 1185-1187.


Entry2-amino-3-

picoline (mol %)A/B

Isolated yield of

A (%)

1 0 0/100 0

2 10 58/42 14

3 20 85/15 57

4 50 85/15 70

5 70 90/10 80

6 100 93/7 83



Hydroacylation with aldehydes


Ph H

O(Ph3P)3RhCl (5 mol%)

2-amino-3-picoline 30 mol%)benzoic acid ( 10 mol%)

Ph

O

toluene, 150 oC, 1.5 h

CO2Men

+

O

OMen

NN

PhRh

O OMe

n

n = 0: 92 %= 1: 59 %= 2: 49 %


Hydroacylation with alcohols


N N

TransitionMetal[M]

R X

O

R OH

N N

R1

Me

N N

Me

R

O

R1 R

O

YR

Y

O

R1


[M]R

X

N NH2

Me

R OH

Y

O

R O

R

N N

R2

Me

R

R3

O

R2 R

R3

R3R2

Y = OR, NR'


Fate of the catalyst?

Can it be recycled ???

A + B C + D

Reactant Products

Catalyst

� Polymer supported catalysis

� Extractions

� Recyclable self-assembly-supported catalyst

Catalyst recovery approaches

Dinh, L. V.; Gladysz, J. A. Angew. Chem. Int. Ed. 2005, 44, 4095-4097.

Hydrogen-bond assisted metal organic cooperative catalysis

Hydroacylation with alcohols

Jun, C. H.; Park, J. H.; Parh, J. W. J. Org. Chem. 2008. 73. 5598-5601.

Entry R1 R2 Time

(h)

Isolated yield (%)

1st 2nd 3rd 4th 5th 6th

1 H t-Bu 6 78 83 86 76 76 77

2 H n-Bu 6 70 84 84 78 75 80

3 CF3t-Bu 6 83 89 81 77 77 82

4 MeO t-Bu 3 77 71 81 78 72 78

Hydrogen-bond assisted metal organic cooperative catalysis

Jun, C. H.; Park, J. H.; Parh, J. W. J. Org. Chem. 2008. 73. 5598-5601.

Summary

� Advantages

� Enables unprecedented transformations not currently possibly by use

of each catalytic systems alone.

� Good stereo and regio control.

� One pot approach. Reduce waste and less time.

� Drawbacks

� Catalysis compatibility.

� Functional group tolerance.

� Aminocatalysist are confined to aldehyde and ketone functionality.

Acknowledgments

Prof. Aaron Odom

Prof. Barbak Borhan

Mr. Steve Difranco

Thank you for your attention

Mr. Nick Maciulis

Mr. Philip Bentley

Mrs. Hashini Galhena Dissanayake

cooperative dual catalysis: combining transition metal catalysis

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