CATALYTIC FUJIWARA-MORITANI
REACTION. CHALLENGES IN C-H
ACTIVATION AND CATALYST
OXIDATION.
Laura Ruiz Espelt
Yoon Group
University of Wisconsin-Madison
Literature Seminar
April 7, 2011
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• Discovered in 1968 independently by Mizoroki and Heck
• Attractive transformation for C-C bond formation
• Richard F. Heck obtained the Nobel Prize on 2010
• Intensively developed from synthetic and mechanistic point of view
Oestrich, M. The Mizoroki-Heck Reaction; John Wiley & Sons, 2009
2
Garg, N.K.; Caspi, D.D.; Stoltz, B.M. Synlett 2006, 18, 3081
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Garg, N.K.; Caspi, D.D.; Stoltz, B.M. Synlett 2006, 18, 3081
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Garg, N.K.; Caspi, D.D.; Stoltz, B.M. Synlett 2006, 18, 3081
5
Moritani, I.; Fujiwara, Y. Tetrahedron Lett. 1967, 12, 1119
Fujiwara, Y.; Moritani, I.; Matsuda, M.; Teranishi, S. Tetrahedron Lett. 1968, 5, 633
6
Fujiwara, Y.;Asano, R.; Moritani, I.; Teranishi, S. J. Org. Chem. 1976, 41, 1681
Fujiwara, Y.;Asano, R.; Moritani, I.; Teranishi, S.
J. Org. Chem. 1976, 41, 1681
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Fujiwara, Y.; Moritani, I.; Danno, S.; Asano, R.; Teranishi, S. J. Am. Chem. Soc. 1969, 7166
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Oestrich, M. The Mizoroki-Heck Reaction; John Wiley & Sons, 2009, p. 14
Fujiwara, Y.; Moritani, I.; Danno, S.; Asano, R.; Teranishi, S.
J. Am. Chem. Soc. 1969, 7166
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Challenge 1: C-H Activation
Challenge 2: Pd(0) Oxidation
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1.
2.
C-H bonds easier to activate
Complete ortho regioselectivity for symmetrical substrates
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Satoh and Miura (2009)
Umeda N.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2009, 74, 7094
Shi (2007)
Cai, G.; Fu, Y.; Li, Y.; Wan, X.; Shi, Z. J. Am. Chem. Soc. 2007, 129, 7666
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-
Entry into phthalide core
-
Reaction catalyzed by [Pd] cyclizes after first vinylation
-
Reaction catalyzed by [Rh] suffers a second vinylation before the cyclization step
-
No mechanistic insight
Ueura, K.; Satho, T.; Miura, M. Org. Lett. 2007, 9, 1407-1409
Miura, M.; Tsuda, T.; Satoh, T.; Pivsa-Art, S.; Nomura, M. J. Org. Chem. 1998, 63, 5211-5215
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Ryabov, A.D.; Sakodinskaya, I.K.; Yatsimirsky, A.K. J. Chem. Soc. Dalton Trans. 1985, 2629
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BP86 / 6-31G**
Davies, D.; Donald, S.M.A.; Macgregor, S.T. J. Am. Chem. Soc. 2005, 127, 13754
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Short distance between Pd and H
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Elongated C-H bond
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No charge change in aromatic ring
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Maehara, A.; Tsurugi, H.; Satoh, T.; Miura, M. Org. Lett. 2008, 10, 1159
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Ferreira, E.; Stoltz, B.M. J. Am. Chem. Soc. 2003, 125, 9578
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Zhang, Y.; Shi, B.; Yu, J.Q. J. Am. Chem. Soc. 2009, 131, 5072
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0.05 Å
longer than
Pd(Pyr)2(OAc)2
-
Origin of meta selectivity still unclear
Zhang, Y.; Shi, B.; Yu, J.Q. J. Am. Chem. Soc. 2009, 131, 5072
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Wang, D.; Engle, K.; Shi, B.; Yu, J.Q. Science. 2010, 327, 315
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Engle, K.M.; Wang, D.; Yu, J.Q. J. Am. Chem. Soc. 2010, 132, 14137
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Engle, K.M.; Wang, D.; Yu, J.Q. J. Am. Chem. Soc. 2010, 132, 14137
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Engle, K.M.; Wang, D.; Yu, J.Q. J. Am. Chem. Soc. 2010, 132, 14137
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 Many improvements achieved since Fujiwara’s initial observations
 Two main tactics used to achieve regioselectivity:
1. Directing groups- site selective palladation
2. Ligands- not fully understood
 More “synthetically appealing” directing groups design: traceless directing groups
 Future of ligands to direct reactivity and selectivity
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Fujiwara (1968)
Fujiwara, Y.; Moritani, I.; Matsuda, M.; Teranishi, S. Tetrahedron Lett. 1968, 35, 3863
Itahara (1983)
Itahara, T.; Ikeda, M.; Sakakibara, T. J. Chem. Soc. Perkin Trans 1. 1983, 1361
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“Green Oxidants”: O2
Pros: - Environmentally friendly
- Lower cost
- Increase in atom efficiency
- Facilitate product isolation
Stahl, S. Angew. Chem. Int. Ed. 2004, 43, 3400
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“Green Oxidants”: O2
Cons: - O2 requires rigorous safety handling
- Slow electron transfer compared to
decomposition of the reduced metal
Solution: - Use of ligands to stabilize Pd0 so that is stable under oxidative conditions
- Use an electron-transfer mediator to carry the electrons from Pd0 to terminal
“green oxidant’
Piera, J.; Backvall, J.E. Angew. Chem. Int. Ed. 2008, 47, 350610
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Yokota, T.; Tani, M.; Sakaguchi, S. Ishii, Y. J. Am. Chem. Soc. 2003, 125, 1476
Want, J.; Yang, C.; Liu, L.; Guo, Q. Tet. Letters. 2007, 48, 5449
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Shue, R.S. Chem. Commun. 1971, 1510
Dams, M.; De Vos, D.E.; Celen, S.; Jacobs, P.A. Angew. Chem. Int. Ed. 2003, 42, 3512
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Ferreira, E.; Stoltz, B.M. J. Am. Chem. Soc. 2003, 125, 9578
2 equiv
Engle, K.M.; Wang, D.; Yu, J.Q. J. Am. Chem. Soc. 2010, 132, 14137
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Challenge: Use a Directing Group that
acts also as the Oxidant:
OXIDIZING DIRECTING GROUPS
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Rakshit, S.; Grohmann, C.; Besset, T.; Glorius, F. J. Am. Chem. Soc. 2011, 133, 2350
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Wu,J.; Cui, X.; Chen, L.; Jiang, G.; Wu, Y. J. Am. Chem. Soc. 2009, 131, 13888
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Rakshit, S.; Grohmann, C.; Besset, T.; Glorius, F. J. Am. Chem. Soc. 2011, 133, 2350
Wu,J.; Cui, X.; Chen, L.; Jiang, G.; Wu, Y. J. Am. Chem. Soc. 2009, 131, 13888
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Cho, S.H.; Hwang, S.J.; Chang, S.
J. Am. Chem. Soc. 2008, 130, 9254
Wu,J.; Cui, X.; Chen, L.; Jiang, G.; Wu, Y.
J. Am. Chem. Soc. 2009, 131, 13888
Pauterau, F.W.; Besset, T.; Glorius, F.
Angew. Chem. Int. Ed. 2011, 50, 1064
Rakshit, S.; Grohmann, C.; Besset, T.; Glorius, F.
. Am. Chem. Soc. 2011, 133, 2350-2353
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
Two main tactics used to achieve
regioselectivity:
1.Directing groups
2. Ligands
 Oxidation on catalyst achieved by:
1. Stoichiometric oxidants such as Cu(OAc)2
or AgOAc
2. Oxygen in the presence of electrontransfer-mediators such as Cu(OAc)2 or
polyoxometallate acids
3. Oxygen as sole oxidant in the presence
of ligands to stabilize the metal
 Oxidizing directing group opens new avenues for this chemistry
 Advantages/ disadvantages have to be evaluated individually
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Thank you!
Professor Tehshik Yoon
Kat Myhre
The Yoon Group
Practice Talk Attendees:
Travis Blum
Jamie Chen
Megan Cismesia
Juana Du
Olga Dykhno
Elliot Farney
Anna Hurtley
Shishi Lin
Zic Lu
Jon Parrish
Derek Salter
Liz Tyson
Kevin Williamson
Adam Weinstein