cooperative dual catalysis: combining transition metal catalysis
TRANSCRIPT
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
Cooperative Dual Catalysis
2. Combination of Organocatalysis and Biocatalysis
3. Combining Photoredox catalysis and Organocatalysis
4. Combining Transition Metal catalysis and Organocatalysis
1. Anodic Oxidation 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
Jensen, K. L.; Franke, T. P.; Jorgensen, K. A. Angew. Chem. Int. Ed. 2010, 49, 129-133.
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
1. Anodic Oxidation and Organocatalysis
Jensen, K. L.; Franke, T. P.; Jorgensen, K. A. Angew. Chem. Int. Ed. 2010, 49, 129-133.
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
MacMillan, D. W. C. Nature. 2008. 455, 304-308.
Substrate Catalyst Activation modes# of new
reactionsNew reaction variants
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
Substrate Catalyst Activation modes# of new
reactionsNew reaction variants
50
Conjugate amination
Conjugate oxygenation
Cyclopropanation
Ketone Diels-Alder
reaction
Mukaiyama-Michael
reaction
Generic modes of activation used in organocatalysis
Iminium catalysis
N
N
O
t-BuPh
RNu:
LUMO activation
Substrate Catalyst Activation modes# of new
reactionsNew reaction variants
4
α-Allylation
α-Enolation
α-Vinylation
α-Heteroarylation
SOMO catalysis
MacMillan, D. W. C. Nature. 2008. 455, 304-308.
Substrate Catalyst Activation modes# of new
reactionsNew reaction variants
2
Acyl-Pictet=Spengler
Reaction
Oxocarbenium
addition reaction
Generic modes of activation used in organocatalysis
Counterion catalysis
C5H11nN
N N
NO
St-Bu
R'''
H HCl
X R''
R
R'
Nu:
LUMO activationLUMO activation
MacMillan, D. W. C. Nature. 2008. 455, 304-308.
4. Combining transition metal catalysis and organocatalysis
� Combining transition metal complex and aminocatalysis
� Combining transition metal complex and Bronsted acids
� Chelation assisted metal organic cooperative catalysis
� Hydrogen-bond assisted metal organic cooperative catalysis
� Combining transition metal complex and aminocatalysis
� Combining transition metal complex and Bronsted acids
4. Combining transition metal catalysis and organocatalysis
� Combining transition metal complex and Bronsted acids
� Chelation assisted metal organic cooperative catalysis
� Hydrogen-bond assisted metal organic cooperative catalysis
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
Binder, J. T.; Crone, B.; Haug, T. T.; Menz, H.; Kirsch, S. F. Org. Lett. 2008. 10. 1025–1028.
Proposed mechanism for carbocyclization of aldehydes with alkynes
Binder, J. T.; Crone, B.; Haug, T. T.; Menz, H.; Kirsch, S. F. Org. Lett. 2008. 10. 1025–1028.
Direct carbocyclization of aldehydes with alkynes
Binder, J. T.; Crone, B.; Haug, T. T.; Menz, H.; Kirsch, S. F. Org. Lett. 2008. 10. 1025–1028.
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 [%]
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.
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
Carbocyclization of aldehydes with alkynes intramolecular approach
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.
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
Usui, I.; Schmidt, S.; Breit, B. Org. Lett. 2009. 11. 1453-1453.
O
PPh2 PPh2
Xantphos
L L=
Allylic alkylation of enolizable ketones and aldehydes with allylic alcohols
Entry Ketone/Aldehyde Products Yield %
1 89
2 75
3 96
O
Ph
Usui, I.; Schmidt, S.; Breit, B. Org. Lett. 2009. 11. 1453-1453.
4 85
5 78
6 81
7 73
O
O O
O
Ph
Cooperative Dual Catalysis
4. Combining transition metal catalysis and organocatalysis
� Combining transition metal complex and aminocatalysis
� Combining transition metal complex and Bronsted acids� Combining transition metal complex and Bronsted acids
� Chelation assisted metal organic cooperative catalysis
� Hydrogen-bond assisted metal organic cooperative catalysis
� 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
Rueping.; M. Antonchick.; P. A, Brinkmann, C. Angew. Chem. Int. Ed. 2007, 46,6903-6906.
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.
Asymmetric alkynylation of imines
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
Rueping.; M. Antonchick.; P. A, Brinkmann, C. Angew. Chem. Int. Ed. 2007, 46,6903-6906.
Asymmetric alkynylation of imines
Rueping.; M. Antonchick.; P. A, Brinkmann, C. Angew. Chem. Int. Ed. 2007, 46,6903-6906.
� 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.
4. Combining transition metal catalysis and organocatalysis
� Combining transition metal complex and aminocatalysis
� Combining transition metal complex and Bronsted acids� Combining transition metal complex and Bronsted acids
� Chelation assisted metal organic cooperative catalysis
� Hydrogen-bond assisted metal organic cooperative catalysis
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.
Chelation assisted metal organic cooperative catalysis
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
Jun, C. H.; Lee, J. A.; Ahn, B. I.; Park, Y. J. Chem. Commun. 2008. 1185-1187.
Chelation assisted metal organic cooperative catalysis
Hydroacylation with aldehydes
Jun, C. H.; Lee, J. A.; Ahn, B. I.; Park, Y. J. Chem. Commun. 2008. 1185-1187.
Chelation assisted metal organic cooperative catalysis
Hydroacylation with aldehydes
Jun, C. H.; Lee, J. A.; Ahn, B. I.; Park, Y. J. Chem. Commun. 2008. 1185-1187.
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 %
Chelation assisted metal organic cooperative catalysis
Hydroacylation with alcohols
Jun, C. H.; Lee, J. A.; Ahn, B. I.; Park, Y. J. Chem. Commun. 2008. 1185-1187.
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
Chelation assisted metal organic cooperative catalysis
[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'
Jun, C. H.; Lee, J. A.; Ahn, B. I.; Park, Y. J. Chem. Commun. 2008. 1185-1187.
4. Combining transition metal catalysis and organocatalysis
� Combining transition metal complex and aminocatalysis
� Combining transition metal complex and Bronsted acids� Combining transition metal complex and Bronsted acids
� Chelation assisted metal organic cooperative catalysis
� Hydrogen-bond assisted metal organic cooperative catalysis
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.