Transcript Slide 1

Platinum-Catalyzed Enyne Cycloisomerizations:
The Intervention of Cyclopropyl Platinacarbenes
Kyle DeKorver
Hsung Research Group
2 April 2009
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Reaction Nomenclature
Metathesis Ξ Skeletal Rearrangement
Pt
Pt
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Why Enyne Cycloisomerization is Powerful
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Inherently atom economical
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Significantly increase structural complexity
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Enynes are easily synthesized
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Huge diversity of products
Nevado, C.; Charruault, L.; Michelet, V.; Nieto-Oberhuber, C.; Muñoz, M.P.; Mendéz, M.; Rager, M-N.; Genêt, J-P.;
Echavarren, A. Eur. J. Org. Chem. 2003, 706.
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Enyne Cycloisomerization Pathways
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Beginning with Botrydianes
Botrydial
Trost, B.; Chang, V. Synthesis 1993, 824.
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Two Possible Mechanistic Pathways?
Type A
Chatani, N.; Furukawa, N.; Sakurai, H.; Murai, S. Organometallics 1996, 15, 901.
Type B
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Trapping of Carbenoid Intermediate
Chatani, N.; Kataoka, K.; Murai, S.; Furukawa, N.; Seki, Y. J. Am. Chem. Soc. 1998, 120, 9104.
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Possible Enyne-Metal Complexes
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Type A vs Type B “Metathesis”
Chatani, N.; Kataoka, K.; Murai, S.; Furukawa, N.; Seki, Y. J. Am. Chem. Soc. 1998, 120, 9104. Fürstner, A.; Szillat, H.; Stelzer, F.
J. Am. Chem. Soc. 2000, 122, 6785. Oi, S.; Tsukamoto, I.; Miyano, S.; Inoue, Y. Organometallics 2001, 20, 3704.
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Combined Working Mechanism
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Enyne “Metathesis” Product Diversity
Chatani, N.; Furukawa, N.; Sakurai, H.; Murai, S. Organometallics 1996, 15, 901. Fürstner, A.; Stelzer, F; Szillat, H. J. Am. Chem.
Soc. 2001, 123, 11863.
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Enantioselective Formal Total Synthesis of Roseophilin
Trost, B.; Doherty, G. J. Am. Chem. Soc. 2000, 122, 3801. Fürstner, A.; Weintritt, H. J. Am. Chem. Soc. 1998, 120, 2817.
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[4.1.0] Bicycloheptene Formation
• Heteroatom alters reactivity of enyne
• Divergence could indicate common reactive intermediate
Fürstner, A.; Szillat, H.; Stelzer, F. J. Am. Chem. Soc. 2000, 122, 6785. Fürstner, A.; Stelzer, F; Szillat, H. J. Am. Chem. Soc.
2001, 123, 11863.
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Mechanism For [4.1.0] Bicycloheptene Formation
Fürstner, A.; Stelzer, F; Szillat, H. J. Am. Chem. Soc. 2001, 123, 11863.
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Functionalization of [4.1.0] bicycloheptenes
Nevado, C.; Ferrer, C.; Echavarren, A. Org. Lett. 2004, 6, 3191.
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Enantioselective Bicycloheptene Formation
Brissy, D.; Skander, M.; Retailleau, P.; Marinetti, A. Organometallics 2007, 26, 5782.
Brissy, D.; Skander, M.; Retailleau, P.; Frison, G.; Marinetti, A. Organometallics 2009, 28, 140.
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Cyclobutene Formation
Fürstner, A.; Davies, P.; Gress, T. J. Am. Chem. Soc. 2005, 127, 8244.
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Cyclobutenes From Allenynes
Matsuda, T.; Kadowaki, S.; Goya, T.; Murakami, M. Synlett 2006, 575.
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Mechanistic Basis for Divergence of Reaction
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Alkoxy- and Hydroxycyclizations
Mendez, M.; Muoz, M.; Echavarren, A. J. Am. Chem. Soc. 2000, 122, 11549. Mendez, M.; Muoz, M.; Nevado, C.;
Cárdenas, D.; Echavarren, A. J. Am. Chem. Soc. 2001, 123, 10511.
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Factors Influencing Regioselectivity of Addition
Mendez, M.; Muoz, M.; Nevado, C.; Cárdenas, D.; Echavarren, A. J. Amer. Chem. Soc. 2001, 123, 10511.
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Indenol and Azulenol Derivatives
Yeh, M-C.; Tsao, W-C.; Cheng, S-T. J. Org. Chem. 2008, 73, 2902.
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Enantioselective Hydroxycylization
Charruault, L.; Michelet, V.; Taras, R.; Gladiali, S.; Genet, J-P.; Chem. Commun. 2004, 850.
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Enantioselective Hydroarylation - Cycloisomerization
Toullec, P.; Chao, C-M.; Chen, Q.; Gladiali, S.; Genêt, J-P.; Michelet, V. Adv. Synth. Cat. 2008, 350, 2401.
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Mechanistic Basis for Divergence of Reaction
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Cycloisomerization With Propargylic alcohols
Lin, M-Y.; Das, A.; Liu, R-S. J. Am. Chem. Soc. 2006, 128, 9340. Tang, J-M.; Bhunia, S.; Sohel, S.M.A..; Lin, M-Y.; Liao, H-Y.;
Datta, S.; Das, A.; Liu, R-S. J. Am. Chem. Soc. 2007, 129, 15677.
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Mechanistic Studies
Tang, J-M.; Bhunia, S.; Sohel, S.M.A.; Lin, M-Y.; Liao, H-Y.; Datta, S.; Das, A.; Liu, R-S. J. Amer. Chem. Soc. 2007, 129, 15677.
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Ene-diynes With Propargylic Acetates
Lu, L.; Liu, X-Y.; Shu, X-Z.; Yang, K.; Ji, K-G.; Liang, Y-M. J. Org. Chem. 2009, 74, 474. Mainetti, E.; Mouries, V.; Fensterbank, L.;
Malacria, M.; Marco-Contelles, J. Agnew. Chem. Int. Ed. 2002, 41, 2132.
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Concluding Remarks
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Product diversity via small changes in enyne
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Atom economical
– Recycleability of catalyst ( > 5 times)
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Scalability of reactions (multigram)
Moreau, X.; Hours, A.; Fensterbank, L.; Goddard, J.P.; Malacria, M.; Thorimbert, S. J. Organometallic Chem. 2009, 694, 561.
Miyanohana, Y.; Inoue, H.; Chatani, N. J. Org. Chem. 2004, 69, 8541.
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Concluding Remarks
• Complex scaffolds with high levels of diastereoselectivity
• Asymmetric variations with good ee’s
• Limitation: Heteroatom or geminally disubstituted tether required
• Cycloisomerization of 1,n enynes
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Mechanistic Basis for Divergence of Reaction
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Acknowledgements
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Professor Richard Hsung
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Practice Talk Attendees
– Dr. Yu Zhang
– Dr. Yu Tang
– Dr. Ryuji Hayashi
– Andrew Lohse
– Gang Li
– Grant Buchanan
– John Feltenberger
– Jin Haek Yang
– Jenny Werness
– Hongyan Li
– Ting Lu
– Yonggang Wei
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Kat Myhre
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Brittland DeKorver
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Hsung Group
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All of you for listening!