Transcript Hydrogen Bond Catalysis - Test Page for Apache Installation

Hydrogen-Bond Catalysis
For reviews see:
M. S. Taylor, E. N. Jacobsen, Angew. Chem. Int. Ed. 2006, 45, 1520-1543
A. G. Doyle, E. N. Jacobsen, Chem. Rev., 2007, 5713-5743
Nadia Fleary-Roberts
03/02/10
A brief history…
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Lewis acids has dominated enantioselective catalysis
acceleration of Diels Alder reaction with AlCl3
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Yates P.; Eaton P., J.Am. Chem. Soc. 1960, 82, 4436
• Wynberg reported asymmetric conjugate addition reactions with cinchona alkaloids
bearing a free hydroxyl group.
Hiemstra H.; Wynberg H., J. Am. Chem. Soc. 1981, 103, 417-430
•Jacobsen reported asymmetric hydrocyanation of aliphatic and
aromatic aldehydes
Sigman, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 1998, 120, 4901
Lewis acid catalysis
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Highly tunable
Can vary counter ion, chiral ligand
Lewis base/acid interactions are
stronger
Interactions are more directional
H-bond catalysis
Moderately tunable
Active catalyst
Potentially recoverable
What is a hydrogen bond?
“An XH···A interaction is called a ,hydrogen bond', if 1. it constitutes a
local bond, and 2. XH acts as a proton donor to A.”
Steiner, Angew. Chem. Int. Ed. 2002, 41, 48
Strength can vary from 0.4 to 40 kcalmol-1.
Role of H-bonds:
DNA base pairing
Ligand/receptor binding
G.A. Jeffrey, An Introduction to Hydrogen Bonding, Oxford University Press, New York, 1997
Most Hydrogen bonding in H-bond catalysis is of moderate strength
Brønsted acids can accelerate organic reactions by either of two
fundamental mechanisms:
Specific acid catalysis
•protonation of the electrophile in a
prior to nucleophilic attack
General acid catalysis
•proton transfer to the transition
state in the rate-determining step
Modes of bonding
Double H-bond donors
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Increased strength and directionality
e.g. Ureas, thioureas, Guanidinium and Amidinium ions
X = O, S
Single H-bond donors
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Less strength than double H-bond donors
Less directionality
•e.g. Diols, biphenols, chiral phosphoric acids
Bifunctional catalysis
•a single or dual H-bond donor site flanked by sites for
secondary interaction with substrates.
e.g. Proline and proline analogs, cinchona alkaloids and derivatives
Double H-bond donors
Ureas and Thioureas
b R1 = Bn, R2 = H, R3 = OCH3, X= S
c R1 = Bn, R2 = H, R3 = OCOtBu, X = O
d R1 = R2 = CH3, R3 = OCOtBu, X =S
e R1 = Bn, R2 = CH3, R3 = tBu, X = S
•Originally developed as ligands for
lewis acidic metals.
•Most applicable class of chiral Hbond donors
•Can promote addition of a range of
nucleophiles
•Imine activation
Double H-bond donors
•Diels Alder reaction
Wittkopp A.; Schreiner P. R., Chem. Eur. J. 2003, 9,
•Aza Baylis-Hillman reaction
e R1 = Bn, R2 = CH3, R3 = tBu, X = S
Raheem, I. T.; Jacobsen, E. N. AdV. Synth. Catal. 2005, 347, 1701
Double H-bond donors
•Asymmetric Strecker reaction
•Scaleable catalytic synthesis
•Imines derived from alky, aryl, heteroaryl aldehydes
•Aqueous cyanide salts
•Robust catalyst
•Access to the (R)-enantiomer of tert-leucine
Zuend S.J.; Coughlin M. P.; Lalonde M. P.; Jacobsen E. N., Nature, 2009, 461, 968
Double H-bond donors
•Asymmetric Pictet Spengler reaction
Taylor, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 10558
Bifunctional Thiourea derivatives
•1,4- additions
Takemoto catalyst
T. Okino, Y. Hoashi, Y. Takemoto, J. Am. Chem. Soc. 2003, 125, 12672 – 12673
B.-J. Li, L. Jiang, M. Liu, Y.-C. Chen, L.-S. Ding, Y. Wu, Synlett 2005, 4, 603
•Aza-henry reaction-(addition of nitroalkanes to imines )
T. Okino, S. Nakamura, T. Furukawa, Y. Takemoto, Org. Lett. 2004, 6, 625
•1,2-additions
D. E. Fuerst, E. N. Jacobsen, J. Am. Chem. Soc. 2005, 127, 8964
•Other thiourea catalysts
efficient catalyst for Baylis-Hillman reactions
Double H-bond donors
Guanidinium and Amidinium ions
•Capable of double H-bond interactions
•Are positively charged so result in increased H-bond
donor abiltity.
•Strecker reaction
T. Steiner, Angew. Chem. 2002, 114, 50; Angew. Chem. Int. Ed. 2002, 41, 48 .
Double H-bond donors
Amidinium catalysed reactions
•Nitro-Mannich reaction
•Diels Alder reaction
k
Ar = 3,5-(CF3)2C6H3
Schuster T.; Bauch M.; Durner G.; Gmbel M. W.; Org. Lett. 2000, 2, 179 – 181.
Single H-bond donors
Diols and Biphenols
•Hetero Diels Alder reaction catalysed by chiral diols
Huang Y.; Unni, A. K.; Thadani, A. N.; Rawal V.H., Nature, 2003, 424, 146
•Baylis-Hillman reaction -Binol derivatives
Single H-bond donors
•Chiral phosphoric acids
•Mannich reaction
T. Akiyama, J. Itoh, K. Yokota, K. Fuchibe, Angew. Chem. 2004, 116, 1592 – 1594
Angew. Chem. Int. Ed. 2004, 43, 1566 –1568
D. Uraguchi, M. Terada, J. Am. Chem. Soc. 2004, 126, 5356 – 5357
•Reductive amination
HEH = ethyl Hantzsch ester
R. I. Storer, D. E. Carrera, Y. Ni, D. W. C. Macmillan, J. Am. Chem. Soc. 2006, 128, 84
Bifunctional catalysis
Proline catalysed reactions
•enatioselective aldol cyclizations
Z. G. Hajos, D. R. Parrish, (Hoffman-La-Roche),
German Patent DE 2102623, 1971 [Chem. Abstr. 1972, 76, 59072];
Proposed mechanism for proline catalysed transformations
A. G. Doyle, E. N. Jacobsen, Chem. Rev., 2007, 5713-5743
Proline analogues
u higher yields and selectivity compared to proline
x increased solubility
Tetrazole is a pharmacore for carboxylic acid
Bifunctional catalysis
Cinchona alkaloids
•Enatioselective conjugate additions
•Baylis-Hillman reaction
Nakano A. et . al. 2006, 62, 381
Iwabuchi Y. et. al. J. Am. Chem. Soc. 1999, 121, 10219
Connon S.J., Chem. Comm., 2008, 2499
Bifunctional catalysis
Oligiopeptides
• Cyclo(l-phenylalanine-l-histidine) hydrocyanation of aldehydes
Uncertainty concerning mechanism
S. Inoue, J.-I. Oku, J. Chem. Soc. Chem. Commun. 1981, 229 –230
Summary
• A dynamic and large area of research which is
continuing to be explored
• Applicable to a wide number of transformations
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