A speedy marriage in supramolecular catalysis Cross-coupling reactions can be accelerated by trapping the metal catalyst in a confined space By KaKing Yan and Makoto Fujita
E
nzymes catalyze a wide range of slow biological reactions by crafting their local environments to accommodate and interact with reactants (1). Chemists aiming to design synthetic systems with enzyme-like activity have previously introduced conventional catalysts directly into an enzyme pocket to facilitate reactions of interest (2). On page 1235 of this issue, Kaphan et al. (3) use a related strategy to speed up an alkyl-alkyl cross-coupling reaction that is prohibitively slow on its own (4). However, instead of a natural enzyme, the authors use a synthetic cocatalyst that forms a cage around Department of Department of Applied Chemistry, University of Tokyo, Tokyo, Japan. E-mail: [email protected]; [email protected]
their organometallic catalysts. The synthetic enhances the rate of a key step of the reaction, reductive elimination, by at least a factor of seven. The authors use a supramolecular cage that is self-assembled from organic ligand molecules (linkers) and metal ions (nodes) (see the figure, left). The host molecule is highly anionic and contains a hydrophobic cavity that favors entrapment of cationic compounds, including different organic and organometallic molecules. In such host-guest systems, noncovalent interactions—such as aromatic interactions, electrostatics and, hydrophobic effects—govern the interaction between the host and guest molecules. These comparatively weak forces can stabilize reactive intermediates (5−7), accelerate chemical reactions (8), and direct chemical processes to produce nonthermodynamic products (9−11).
Supramolecular cage O O
–
–
11–
–
NH
O
Catalytic cycle
O
12– R3P—Au
CH3–CH3 Cross-coupling product is released
HN
3
!
O
–
O
R3P—Au
[Ga4L6]12–
Reductive elimination
1
R3P—Au—I
Au(I) species is trapped by iodide
Dissociation of cationic Au(I) complex
L Ga3+
@
I
12–
11– Space-flling model R3P
Au Me
Me
ILLUSTRATION: P. HUEY/SCIENCE
Entrapped Au(III) species
Transient empty host 1
Encapulation of cationic Au(III) complex
2 @
I +
Caged gold. (Left) Kaphan et al. use a synthetic metal-organic assembly as an enzyme mimic catalyst. L = N,N’-bis(2,3-dihydroxybenzoyl)-1,5diaminonaphthalene. (Right) They performed a general reaction in which a highly anionic metal-ligand cluster catalyst facilities facile reductive elimination of gold (III) dialkyl complex in mild condition.
R3P Me
!
Au
Me
R 3P
I Au
Me Me R = Me, Et Equilibrium of ionized Au(III) complex
SCIENCE sciencemag.org
4 DECEMBER 2015 • VOL 350 ISSUE 6265
Published by AAAS
1165
Downloaded from www.sciencemag.org on December 3, 2015
A key property of enzyme catalysis is substrate size exclusion. The host’s recognition of appropriately shaped and sized guests is often used in nature but rarely incorporated into standard homogeneous or heterogeneous catalysis. Kaphan et al. found that, in their system, the size of the phosphine ligand on the guest complexes is crucial. If this ligand is too big, the substrate is neither entrapped nor catalyzed. If the ligand is too small, catalyst deactivation is observed. The vast majority of chemical reactions are catalyzed by transition metal compounds. In many of these processes, reductive elimination is a key product-forming step. In the case of gold-catalyzed reactions, previous studies have suggested that reductive elimination from the Au(III) center proceeds through ligand dissociation before the release of the carbon-carbon bond coupling product (4, 12, 13). Based on their data, Kaphan et al. argue for a different process, in which halide dissociates from the gold complex before it is encapsulated by the host. This generates a transient cationic Au(III) dialkyl complex within the anionic cage cavity. Due to the steric congestion imposed by the cage, the entrapped Au(III) complex spontaneously undergoes alkyl-alkyl cross-coupling to give an alkane product (see the figure, right). This reaction would be very sluggish without the supramolecular cage.
CATA LYS I S
INSIGHTS | P E R S P E C T I V E S
REFERENCES
1. R. Wolfenden, M. J. Snider, Acc. Chem. Res. 34, 938 (2001). 2. T. K. Hyster, L. Knörr, T. R. Ward, T. Rovis, Science 338, 500 (2012). 3. D. M. Kaphan, M. D. Levin, R. G. Bergman, K. N. Raymond, F. D. Toste, Science 350, 1235 (2015). 4. W. J. Wolf, M. S. Winston, F. D. Toste, Nat. Chem. 6, 159 (2014). 5. P. Mal, B. Breiner, K. Rissanen, J. K. Nitschke, Science 324, 1697 (2009). 6. D. J. Cram, M. E. Tanner, R. Thomas, Angew. Chem. Int. Ed. Engl. 30, 1024 (1991). 7. T. Iwasawa, R. J. Hooley, J. Rebek Jr., Science 317, 493 (2007). 8. J. Hastings, D. Fiedler, R. G. Bergman, K. N. Raymond, J. Am. Chem. Soc. 130, 10977 (2008). 9. M. Yoshizawa, M. Tamura, M. Fujita, Science 312, 251 (2006). 10. D. M. Kaphan, F. D. Toste, R. G. Bergman, K. N. Raymond. J. Am. Chem. Soc. 137, 9202 (2015). 11. D. M. Dalton et al., J. Am. Chem. Soc. 137, 10128 (2015). 12. A. Tamaki et al., J. Am. Chem. Soc. 96, 6140 (1974). 13. S. Komiya, J. K. Kochi, J. Am. Chem. Soc. 98, 7599 (1976). 14. Z. Q. Wang, S. M. Cohen, Chem. Soc. Rev. 38, 1315 (2009). 15. D. H. Leung et al., J. Am. Chem. Soc. 129, 2746 (2007). 10.1126/science.aad7245
1166
E C O L O GY
Corridors for people, corridors for nature How can the environmental impacts of roads be reduced? and nutrients and by increased abundances of destructive invasive species (see the ransportation corridors have long graph) (4). Nearly 70% of U.S. forest lies helped to spread people into more rewithin 1 km of a road (5). Effects of road mote places (1). In the past century, a disturbances can be extensive; for example, burgeoning road network has grown carbon sequestration is lowered within 1.5 in concert with the human populakm of tropical forest borders, thus degradtion, connecting people across entire ing ecosystems and reducing the benefits of continents. The immense benefits of roads these forests to people (6). connecting people to agriculture, natural Even more devastating, roads have spillresources, mines, and each other must be over effects, with people clearing newly accesreconciled with their severe environmental sible forests, plowing prairies, and draining degradation. wetlands (see the graph). Be it urban buildRoads directly replace nature on the road’s out in the southeastern United States (7) or path. Low-intensity paths of soil or stone deforestation in the Brazilian Amazon (8), clear natural habitats, and asphalt and conroads spawn clearing of natural areas. crete erase nature entirely. At least 64 million Finally, although roads create corridors for lane-km of paved and unpaved roads cover people, they sever corridors for wild nature. 19 million hectares of Earth’s surface (see Just as people require corridors for transporthe graph) (2). The road network is expected tation, wildlife requires natural corridors for to grow in concert with the growing human their dispersal and migration. Roads isolate population and rising consumption (3). plant and animal populations, thus degradRoads also initiate effects that radiate ing diversity and ecosystems. A single road outward. Natural systems near roads and reduces gene flow by bighorn sheep to levtheir rights of way (the areas reserved and els expected for populations separated by cleared adjacent to them) are degraded by more than 15 km (9). The conflict between exposure to changes in wind, temperature, connections for people and those for wildlife becomes most apparent when Area (millions ha) vehicles and wildlife collide, 700 estimated at 1 to 2 million collisions with large animals annu600 ally that cost $8 billion in the 500 United States alone (10). 400 The effects of roads can be reduced through judicious 300 routing, design, and reduction. 200 Both in developed and develop100 ing regions, such careful road planning can benefit people 0 Roads Roads + Radiating Forested Deforested while minimizing harm to the Right of way efects Brazilian Brazilian Amazon environment (4, 10, 11). Proper Amazon
E
nzymes catalyze a wide range of slow biological reactions by crafting their local environments to accommodate and interact with reactants (1). Chemists aiming to design synthetic systems with enzyme-like activity have previously introduced conventional catalysts directly into an enzyme pocket to facilitate reactions of interest (2). On page 1235 of this issue, Kaphan et al. (3) use a related strategy to speed up an alkyl-alkyl cross-coupling reaction that is prohibitively slow on its own (4). However, instead of a natural enzyme, the authors use a synthetic cocatalyst that forms a cage around Department of Department of Applied Chemistry, University of Tokyo, Tokyo, Japan. E-mail: [email protected]; [email protected]
their organometallic catalysts. The synthetic enhances the rate of a key step of the reaction, reductive elimination, by at least a factor of seven. The authors use a supramolecular cage that is self-assembled from organic ligand molecules (linkers) and metal ions (nodes) (see the figure, left). The host molecule is highly anionic and contains a hydrophobic cavity that favors entrapment of cationic compounds, including different organic and organometallic molecules. In such host-guest systems, noncovalent interactions—such as aromatic interactions, electrostatics and, hydrophobic effects—govern the interaction between the host and guest molecules. These comparatively weak forces can stabilize reactive intermediates (5−7), accelerate chemical reactions (8), and direct chemical processes to produce nonthermodynamic products (9−11).
Supramolecular cage O O
–
–
11–
–
NH
O
Catalytic cycle
O
12– R3P—Au
CH3–CH3 Cross-coupling product is released
HN
3
!
O
–
O
R3P—Au
[Ga4L6]12–
Reductive elimination
1
R3P—Au—I
Au(I) species is trapped by iodide
Dissociation of cationic Au(I) complex
L Ga3+
@
I
12–
11– Space-flling model R3P
Au Me
Me
ILLUSTRATION: P. HUEY/SCIENCE
Entrapped Au(III) species
Transient empty host 1
Encapulation of cationic Au(III) complex
2 @
I +
Caged gold. (Left) Kaphan et al. use a synthetic metal-organic assembly as an enzyme mimic catalyst. L = N,N’-bis(2,3-dihydroxybenzoyl)-1,5diaminonaphthalene. (Right) They performed a general reaction in which a highly anionic metal-ligand cluster catalyst facilities facile reductive elimination of gold (III) dialkyl complex in mild condition.
R3P Me
!
Au
Me
R 3P
I Au
Me Me R = Me, Et Equilibrium of ionized Au(III) complex
SCIENCE sciencemag.org
4 DECEMBER 2015 • VOL 350 ISSUE 6265
Published by AAAS
1165
Downloaded from www.sciencemag.org on December 3, 2015
A key property of enzyme catalysis is substrate size exclusion. The host’s recognition of appropriately shaped and sized guests is often used in nature but rarely incorporated into standard homogeneous or heterogeneous catalysis. Kaphan et al. found that, in their system, the size of the phosphine ligand on the guest complexes is crucial. If this ligand is too big, the substrate is neither entrapped nor catalyzed. If the ligand is too small, catalyst deactivation is observed. The vast majority of chemical reactions are catalyzed by transition metal compounds. In many of these processes, reductive elimination is a key product-forming step. In the case of gold-catalyzed reactions, previous studies have suggested that reductive elimination from the Au(III) center proceeds through ligand dissociation before the release of the carbon-carbon bond coupling product (4, 12, 13). Based on their data, Kaphan et al. argue for a different process, in which halide dissociates from the gold complex before it is encapsulated by the host. This generates a transient cationic Au(III) dialkyl complex within the anionic cage cavity. Due to the steric congestion imposed by the cage, the entrapped Au(III) complex spontaneously undergoes alkyl-alkyl cross-coupling to give an alkane product (see the figure, right). This reaction would be very sluggish without the supramolecular cage.
CATA LYS I S
INSIGHTS | P E R S P E C T I V E S
REFERENCES
1. R. Wolfenden, M. J. Snider, Acc. Chem. Res. 34, 938 (2001). 2. T. K. Hyster, L. Knörr, T. R. Ward, T. Rovis, Science 338, 500 (2012). 3. D. M. Kaphan, M. D. Levin, R. G. Bergman, K. N. Raymond, F. D. Toste, Science 350, 1235 (2015). 4. W. J. Wolf, M. S. Winston, F. D. Toste, Nat. Chem. 6, 159 (2014). 5. P. Mal, B. Breiner, K. Rissanen, J. K. Nitschke, Science 324, 1697 (2009). 6. D. J. Cram, M. E. Tanner, R. Thomas, Angew. Chem. Int. Ed. Engl. 30, 1024 (1991). 7. T. Iwasawa, R. J. Hooley, J. Rebek Jr., Science 317, 493 (2007). 8. J. Hastings, D. Fiedler, R. G. Bergman, K. N. Raymond, J. Am. Chem. Soc. 130, 10977 (2008). 9. M. Yoshizawa, M. Tamura, M. Fujita, Science 312, 251 (2006). 10. D. M. Kaphan, F. D. Toste, R. G. Bergman, K. N. Raymond. J. Am. Chem. Soc. 137, 9202 (2015). 11. D. M. Dalton et al., J. Am. Chem. Soc. 137, 10128 (2015). 12. A. Tamaki et al., J. Am. Chem. Soc. 96, 6140 (1974). 13. S. Komiya, J. K. Kochi, J. Am. Chem. Soc. 98, 7599 (1976). 14. Z. Q. Wang, S. M. Cohen, Chem. Soc. Rev. 38, 1315 (2009). 15. D. H. Leung et al., J. Am. Chem. Soc. 129, 2746 (2007). 10.1126/science.aad7245
1166
E C O L O GY
Corridors for people, corridors for nature How can the environmental impacts of roads be reduced? and nutrients and by increased abundances of destructive invasive species (see the ransportation corridors have long graph) (4). Nearly 70% of U.S. forest lies helped to spread people into more rewithin 1 km of a road (5). Effects of road mote places (1). In the past century, a disturbances can be extensive; for example, burgeoning road network has grown carbon sequestration is lowered within 1.5 in concert with the human populakm of tropical forest borders, thus degradtion, connecting people across entire ing ecosystems and reducing the benefits of continents. The immense benefits of roads these forests to people (6). connecting people to agriculture, natural Even more devastating, roads have spillresources, mines, and each other must be over effects, with people clearing newly accesreconciled with their severe environmental sible forests, plowing prairies, and draining degradation. wetlands (see the graph). Be it urban buildRoads directly replace nature on the road’s out in the southeastern United States (7) or path. Low-intensity paths of soil or stone deforestation in the Brazilian Amazon (8), clear natural habitats, and asphalt and conroads spawn clearing of natural areas. crete erase nature entirely. At least 64 million Finally, although roads create corridors for lane-km of paved and unpaved roads cover people, they sever corridors for wild nature. 19 million hectares of Earth’s surface (see Just as people require corridors for transporthe graph) (2). The road network is expected tation, wildlife requires natural corridors for to grow in concert with the growing human their dispersal and migration. Roads isolate population and rising consumption (3). plant and animal populations, thus degradRoads also initiate effects that radiate ing diversity and ecosystems. A single road outward. Natural systems near roads and reduces gene flow by bighorn sheep to levtheir rights of way (the areas reserved and els expected for populations separated by cleared adjacent to them) are degraded by more than 15 km (9). The conflict between exposure to changes in wind, temperature, connections for people and those for wildlife becomes most apparent when Area (millions ha) vehicles and wildlife collide, 700 estimated at 1 to 2 million collisions with large animals annu600 ally that cost $8 billion in the 500 United States alone (10). 400 The effects of roads can be reduced through judicious 300 routing, design, and reduction. 200 Both in developed and develop100 ing regions, such careful road planning can benefit people 0 Roads Roads + Radiating Forested Deforested while minimizing harm to the Right of way efects Brazilian Brazilian Amazon environment (4, 10, 11). Proper Amazon
