Patrick Robichaux
Tang Group
University of Wisconsin-Madison
Department of Chemistry
Literature Seminar
04/28/2011
1
Overview
History
Preparation
Regioselectivity
Application
2
Overview
History
Preparation
Regioselectivity
Application
3
Evidence for Benzyne
4
Roberts, J. D.; Simmons, H. E.; Carlsmith, L. A.; Vaughan, C. W. J. Am. Chem. Soc. 1953, 75, 3290.
Neutral Benzyne Intermediate?
5
Roberts, J. D.; Simmons, H. E.; Carlsmith, L. A.; Vaughan, C. W. J. Am. Chem. Soc. 1953, 75, 3290.
Singlet or Triplet?
•hν = diradical?
•Benzyne actually
singlet
• singlet-triplet splitting
of 37.5 kcal/mol
•lifetime at least 20 ms
Wittig, G.; Ebel, H. F. Angew. Chem. 1960, 72, 564.
Wentrup, C. Aust. J. Chem. 2010, 63, 979.
6
Overview
History
Preparation
Regioselectivity
Application
7
Traditional Formation of Benzyne
Kitamura, T. Aust. J. Chem. 2010, 63, 987.
Wentrup, C. Aust. J. Chem. 2010, 63, 979.
Pellissier, H.; Santelli, M. Tetrahedron 2003, 59, 701.
8
Synthesis of Silyltriflate
Bronner, S. M.; Garg, N. K. J. Org. Chem. 2009, 74, 8842-8843.
Tadross, P. M.; Gilmore, C. D.; Bugga, P.; Virgil, S. C.; Stoltz, B. M. Org. Lett. 2010, 12, 1224-1227.
Wu, Q.-c.; Li, B.-s.; Shi, C.-q.; Chen, Y.-x. Hecheng Huaxue 2007, 111.
Himeshima, Y.; Sonada, T.; Kobayashi, H. Chem. Lett. 1983, 1211.
Peña, D.; Cobas, A.; Pérez, D.; Guitián, E. Synthesis 2002. 1454.
9
Activation Domino
•Silyl protecting
group tolerant
10
Ikawa, T.; Nishiyama, T.; Nosaki, T.; Takagi, A.; Akai, S. Org. Lett. 2011, 13, 1730.
New Method: C-H activation
CHEAP!
•highly solvent and concentration dependent
•Optimized conditions: Pd(OAc)2 (10 mol %)
Cu(OAc)2 (0.75 equiv.)
1,10-phenanthroline (10 mol %)
K2HPO4 (2 equiv.) , TBAB (1 equiv.)
sulfonane, 4 Å MS
<47% yield
+ side products
11
Cant, A. A.; Roberts, L.; Greaney, M. F. Chemical Communications 2010, 46, 8671-8673.
Overview
History
Preparation
Regioselectivity
Application
12
Regioselectivity: Sterics
13
Diemer, V.; Begaud, M.; Leroux, F. R.; Colobert, F. Eur. J. Org. Chem. 2011, 341.
Regioselectivity: Sterics vs. Electronics
14
Diemer, V.; Begaud, M.; Leroux, F. R.; Colobert, F. Eur. J. Org. Chem. 2011, 341.
Regioselectivity: Electronics
15
Diemer, V.; Begaud, M.; Leroux, F. R.; Colobert, F. Eur. J. Org. Chem. 2011, 341.
Distortion/Interaction Model
Cheong, P. H. Y.; Paton, R. S.; Bronner, S. M.; Im, G. Y. J.; Garg, N. K.; Houk, K. N. J. Am. Chem. Soc. 2010, 132, 1267.
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Im, G. Y. J.; Bronner, S. M.; Goetz, A. E.; Paton, R. S.; Cheong, P. H. Y.; Houk, K. N.; Garg, N. K. J. Am. Chem. Soc. 2010, 132, 17933.
Reactivity of Indolyne Systems
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Im, G. Y. J.; Bronner, S. M.; Goetz, A. E.; Paton, R. S.; Cheong, P. H. Y.; Houk, K. N.; Garg, N. K. J. Am. Chem. Soc. 2010, 132, 17933.
Overview
History
Preparation
Regioselectivity
Application
18
Nucleophilic Additions
19
Acyl-Alkylation of Arynes
20
Tambar, U. K.; Stoltz, B. M. J. Am. Chem. Soc. 2005, 127, 5340.
Acyl-Alkylation of Arynes
21
Tambar, U. K.; Ebner, D. C.; Stoltz, B. M. J. Am. Chem. Soc. 2006, 128, 11752.
Indolines and Isoquinolines
22
Gilmore, C. D.; Allan, K. M.; Stoltz, B. M. J. Am. Chem. Soc. 2008, 130, 1558.
Indolyne: Regioselectivity
Reversal
23
Bronner, S. M.; Goetz, A. E.; Garg, N. K. J. Am. Chem. Soc. 2011, 133, 3832.
Indole Synthesis
E+
E
Yield (%)
H2O
H
75
Bu3SnCl
SnBu3
67
PhCHO
PhC(H)OH
69
Me2CO
Me2COH
73
ClCO2Et
CO2Et
73
PhCH-NPh
PhCHNHPh
59
BrCH2CH2Br
Br
61
24
Barluenga, J.; Fananas, F. J.; Sanz, R.; Fernandez, Y. Chemistry-a European Journal 2002, 8, 2034.
Biaryl Synthesis
25
Milne, J. E.; Buchwald, S. L. J. Am. Chem. Soc. 2004, 126, 13028.
Cycloadditions
26
Enamide Cascade
27
Feltenberger, J. B.; Hayashi, R.; Tang, Y.; Babiash, E. S. C.; Hsung, R. P. Org. Lett. 2009, 11, 3666.
[4+2]
Cycloaddition on
Arene System
28
Nishimura, T.; Nagaosa, M.; Hayashi, T. Chem.Lett.2008, 37, 860.
Metal Free Click Chemistry
29
Lin, Y.; Chen, Y.; Ma, X.; Xu, D.; Cao, W.; Chen, J. Tetrahedron 2011, 67, 856.
Indole Synthesis
30
Nair, V.; Kim, K. H. J. Org. Chem. 1975, 40, 3784.
Transition Metal Reactions
31
3-Component Benzyne
Coupling
Larrosa, I.; Da Silva, M. I.; Gómez, P. M.; Hannen, P.; Ko, E.; Lenger, S. R.; Linke, S. R.; White, A. J. P.; Wilton, D.; Barrett,
A. G. M. J. Am. Chem. Soc. 2006, 128, 14042.
32
3-Component Benzyne
Coupling
Larrosa, I.; Da Silva, M. I.; Gómez, P. M.; Hannen, P.; Ko, E.; Lenger, S. R.; Linke, S. R.; White, A. J. P.; Wilton, D.; Barrett,
A. G. M. J. Am. Chem. Soc. 2006, 128, 14042.
33
Catalytic Carbonylation
34
Chatani, N.; Kamitani, A.; Oshita, M.; Fukumoto, Y.; Murai, S. J. Am. Chem. Soc. 2001, 123, 12686.
Pd-catalyzed
Heck:
Suzuki:
Jayanth, T. T.; Jeganmohan, M.; Cheng, C.-H. Org. Lett. 2005, 7, 2921.
Henderson, J. L.; Edwards, A. S.; Greaney, M. F. Org. Lett. 2007, 9, 5589.
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Conclusions
=
Image from google images
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Acknowledgments
•
•
•
•
Professor Weiping Tang
Tang and Hsung group
Kat Myhre
Practice Talk Attendees:
– Jenny B. Werness
– Dongxu Shu
– Wei Zhang
– Renhe Liu
– Xiaoxun Li
– Dr. Xingzhong Shu
– Suyu Huang
– Andrew G. Lohse
– Kyle Dekorver
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