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Most Recent Advances in Hydroamination:
A Little Supplement to CEM852
Hartwig, J. F. J. Am. Chem. Soc. 2006, ASAPHe, C.; Zhang, J. J. Am. Chem. Soc. 2006, ASAPShibasaki, M.; Qin, H. J. Am. Chem. Soc. 2006, ASAPAckermann, L. Angew. Chem. Int. Ed. 2005, 44, 5972-4Roesky, P. Angew. Chem. Int. Ed. 2005, 44, 7794-8
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Seminar Outline
• Introduction of hydroaminations
• History of hydroaminations
• New catalysts for hydroaminations
• Conclusions
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Organonitrogen Compounds in Industry
Bactericides, herbicides, corrosion inhibitors,extraction agent in theproduction of penicillin,softening agents, wetting agents, dye
fixers,asphalt emulsifiers, pigment dispersing agents,petroleumadditives, a polymer in paper making,textile finishing
Mitomycin (antibiotic) caffeine
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Hydroamination of Alkenes and Alkynes
Overall reaction is thermodynamically favorable with negativereaction entropy, which means high temperature is not able to
overcome high activation barrier.
R2
N
H
R1
R3
[M]R3
NR1R2
R3
NR1R2
R2
N
H
R1
[M]R3
NR1R2
R3
NR1R2
R3
+
+
+
+
Markovnikov Product
Anti-Markovnikov Product
Steinborn, D.; Taube, R. Z. Chem. 1986, 26, 349
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Two General Catalytic Cycles
[M] HNR2
[M]
NHR2
HNR2H
NR2
[M] NHR2
HNR2
[M] HNR2
[M]
H
NR2
[M] NR2
H
NR2
H
[M]
NR2
H
Olefin Activation Amine Activation
Togni, A. J. Am. Chem. Soc. 2000, 122, 4098
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Two Pathways for Breaking the MetalAlky Bond
[M]
NR1R2H
!"Elimination
Reductive
Elimination
NR1R2
NR1R2
H
H[M]
H
H
[M]
+
+
Oxidative Amination Product
HydroAmination Product
Muller, T. E. Chem. Rev. 1998, 98, 675
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First Example of Hydroamination
NH2R'
R
NaR
NHR'
+
R= H,CH3,(CH2)nCH3
R'= H, Et
Condtions: 200°C and 1000atmYields were generally poor with polymeric side-products
Howk, A. et al J. Am. Chem. Soc. 1954, 76, 1899
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Other Metals Used for Hydroamination
Stoichiometric Hg Barluenga, J. et al Synthesis 1975, 116 Ca compounds Crimmin, M. R. et al J. Am. Chem. Soc. 2005, 127, 2042 Lanthanide: La, Sm, Nd… Marks, T. J. et al J. Am. Chem. Soc. 1989, 111, 4108 Late-transition-metal complex: Ir, Rh, Ni, Pd, Pt, and Ru Coulson, D. R. Tetrahedron Lett. 1971, 5, 429 Casalnuovo, A. L. et al J. Am. Chem. Soc. 1988, 110, 6738 Group 4 metal: Ti, Zr, and Hf Bergman, R.G. et al J. Am. Chem. Soc. 1992, 114, 1708
Actinide metal catalyst: U and Th Haskel, A. et al Organometallics 1996, 15, 3773
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Disadvantages of These Catalysts…
Toxic: HgHighly sensitive to moisture and air: Ln, Ti, Zr and Hf.Bad polar-functional-groups tolerance: Ln, group 4 metalsExpensive: late transition metalsModest selectivity, sluggish rates, sometimes requiring stabilizing ligandsor additives: late transition metals
What to do?• Explore more (metal) catalysts• Optimization of conditions by detailed study of mechanisms• Do NOT use any metals:Proton-catalyzed hydroamination Bergman, R. G. et al J. Am. Chem. Soc. 2005, 127, 14542
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Calcium-Mediated Hydroamination Catalyst
Crimmin, M. R. et al J. Am. Chem. Soc. 2005, 127, 2042
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Calcium-Mediated Hydroamination Catalyst
Crimmin, M. R. et al J. Am. Chem. Soc. 2005, 127, 2042
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Calcium-Mediated Hydroamination: Scope
Commensurate with some Ln catalyst (cationic Sc species) Low cost and easily available Environmentally benign Catalyst is not stale Functional group tolerance? Not known yet.
Crimmin, M. R. et al J. Am. Chem. Soc. 2005, 127, 2042
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Zinc-Mediated Hydroamination
Catalyst
Roesky, P. Angew. Chem. Int. Ed. 2005, 44, 7794-8
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Zinc-Mediated Hydroamination
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Zinc-Mediated Hydroamination of Alkene
• Good functional tolerance• Cocatalyst repuired to speed the reaction• Ring size has a larger influence than electronic effects• Slower for alkenes
Roesky, P. Angew. Chem. Int. Ed. 2005, 44, 7794-8
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Gold-Mediated Hydroamination of Alkene
He, C.; Zhang, J. J. Am. Chem. Soc. 2006, ASAP
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Gold-Mediated Hydroamination of Alkene
He, C.; Zhang, J. J. Am. Chem. Soc. 2006, ASAP
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Gold-Mediated Hydroamination of Alkene
He, C.; Zhang, J. J. Am. Chem. Soc. 2006, ASAP
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Gold-Mediated Hydroamination of Alkene: Facts
• Unactivated olefins can work to give Markovnikov product• Nucleophiles: olefins = 1:4• No b-elimination doesn’t occur
• Mechanism study based on NMR shows gold(I) activates olefin, but not TsNH2,which attacks from the oppsite face of gold• The reaction is inhibited by alkylamines or aniline
He, C.; Zhang, J. J. Am. Chem. Soc. 2006, ASAP
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Bismuth-Mediated Hydroamination: Catalyst
• Catalyst: Bi• Cocatalyst repuired: PF6 ligand• Cu is not needed
Shibasaki, M.; Qin, H. J. Am. Chem. Soc. 2006, ASAP
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Bismuth-Mediated Hydroamination: Scope
• Not sensitive to electronic properties of the nucleophiles• Acyclic dienes can work; isomers were produced
Shibasaki, M.; Qin, H. J. Am. Chem. Soc. 2006, ASAP
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Bismuth -Mediated Hydroamination: Mechanism
• Couneranion exchange with PF6- , the coordination site of Bi will be available
Shibasaki, M.; Qin, H. J. Am. Chem. Soc. 2006, ASAP
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Pd-Mediated Hydroamination of Alkene
Problem? Low activities
Hartwig, J. F. J. Am. Chem. Soc. 2006, ASAP
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Pd-Mediated Hydroamination of Alkene
• Good functional tolerance• Excellent yields• More factors influecing the reaction were studied in the paper: bite angle of the ligand, acid effect and counterion effect
1: XantphosPd(η3-allyl)Cl 1: XantphosPd(η3-allyl)OTf
Hartwig, J. F. J. Am. Chem. Soc. 2006, ASAP
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Conclusions
1. New metal-catalyzed hydroaminations were established in 4 months2. More effient3. Better functional group tolerance4. Cheap, readily available and robust to moisture and air
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Happy Chinese New Year
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Dog’s Year, I’ll be 30…
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A Lot Things Changed…
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But My Life Is Still Crappy…
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I Planned a Lot of Things Done Before 30…
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But Still Not Decided Which First…
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Thank You! Questions?