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

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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

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Garg, N.K.; Caspi, D.D.; Stoltz, B.M. Synlett 2006, 18, 3081

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Moritani, I.; Fujiwara, Y. Tetrahedron Lett. 1967, 12, 1119

Fujiwara, Y.; Moritani, I.; Matsuda, M.; Teranishi, S. Tetrahedron Lett. 1968, 5, 633

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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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Fujiwara, Y.; Moritani, I.; Danno, S.; Asano, R.; Teranishi, S.J. Am. Chem. Soc. 1969, 7166

Oestrich, M. The Mizoroki-Heck Reaction; John Wiley & Sons, 2009, p. 14

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Challenge 1: C-H Activation

Challenge 2: Pd(0) Oxidation

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1. C-H bonds easier to activate2. Complete ortho regioselectivity for symmetrical substrates

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Cai, G.; Fu, Y.; Li, Y.; Wan, X.; Shi, Z. J. Am. Chem. Soc. 2007, 129, 7666

Shi (2007)

Satoh and Miura (2009)

Umeda N.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2009, 74, 7094

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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 insightUeura, 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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Davies, D.; Donald, S.M.A.; Macgregor, S.T. J. Am. Chem. Soc. 2005, 127, 13754

BP86 / 6-31G**

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- Short distance between Pd and H

- Elongated C-H bond

- 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 Ålonger 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)

Itahara (1983)

Fujiwara, Y.; Moritani, I.; Matsuda, M.; Teranishi, S. Tetrahedron Lett. 1968, 35, 3863

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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Cons: - O2 requires rigorous safety handling - Slow electron transfer compared to decomposition of the reduced metal

“Green Oxidants”: O2

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

Engle, K.M.; Wang, D.; Yu, J.Q. J. Am. Chem. Soc. 2010, 132, 14137

2 equiv

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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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Pauterau, F.W.; Besset, T.; Glorius, F.Angew. Chem. Int. Ed. 2011, 50, 1064

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

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 electron-

transfer-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!

The Yoon Group

Practice Talk Attendees:

Travis Blum Shishi LinJamie Chen Zic LuMegan Cismesia Jon ParrishJuana Du Derek SalterOlga Dykhno Liz TysonElliot Farney Kevin WilliamsonAnna Hurtley Adam Weinstein

Professor Tehshik Yoon

Kat Myhre