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Platinum-Catalyzed Enyne Cycloisomerizations: The Intervention of Cyclopropyl Platinacarbenes. Kyle DeKorver Hsung Research Group 2 April 2009. Pt. Pt. Reaction Nomenclature. Metathesis Ξ Skeletal Rearrangement. Why Enyne Cycloisomerization is Powerful. Inherently atom economical
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Platinum-Catalyzed Enyne Cycloisomerizations: The Intervention of Cyclopropyl Platinacarbenes Kyle DeKorver Hsung Research Group 2 April 2009
Pt Pt Reaction Nomenclature Metathesis Ξ Skeletal Rearrangement
Why Enyne Cycloisomerization is Powerful • Inherently atom economical • Significantly increase structural complexity • Enynes are easily synthesized • 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.
Beginning with Botrydianes Botrydial Trost, B.; Chang, V. Synthesis1993, 824.
Two Possible Mechanistic Pathways? Type A Type B Chatani, N.; Furukawa, N.; Sakurai, H.; Murai, S. Organometallics 1996, 15, 901.
Trapping of Carbenoid Intermediate Chatani, N.; Kataoka, K.; Murai, S.; Furukawa, N.; Seki, Y. J. Am. Chem. Soc. 1998, 120, 9104.
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. Organometallics2001, 20, 3704.
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.
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.
[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.
Mechanism For [4.1.0] Bicycloheptene Formation Fürstner, A.; Stelzer, F; Szillat, H. J. Am. Chem. Soc. 2001, 123, 11863.
Functionalization of [4.1.0] bicycloheptenes Nevado, C.; Ferrer, C.; Echavarren, A. Org. Lett.2004, 6, 3191.
Enantioselective Bicycloheptene Formation Brissy, D.; Skander, M.; Retailleau, P.; Marinetti, A. Organometallics2007, 26, 5782. Brissy, D.; Skander, M.; Retailleau, P.; Frison, G.; Marinetti, A. Organometallics2009, 28, 140.
Cyclobutene Formation Fürstner, A.; Davies, P.; Gress, T. J. Am. Chem. Soc.2005, 127, 8244.
Cyclobutenes From Allenynes Matsuda, T.; Kadowaki, S.; Goya, T.; Murakami, M. Synlett2006, 575.
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.
Factors Influencing Regioselectivity of Addition Mendez, M.; Muoz, M.; Nevado, C.; Cárdenas, D.; Echavarren, A. J. Amer. Chem. Soc.2001, 123, 10511.
Indenol and Azulenol Derivatives Yeh, M-C.; Tsao, W-C.; Cheng, S-T. J. Org. Chem.2008, 73, 2902.
Enantioselective Hydroxycylization Charruault, L.; Michelet, V.; Taras, R.; Gladiali, S.; Genet, J-P.; Chem. Commun.2004, 850.
Enantioselective Hydroarylation - Cycloisomerization Toullec, P.; Chao, C-M.; Chen, Q.; Gladiali, S.; Genêt, J-P.; Michelet, V. Adv. Synth. Cat.2008, 350, 2401.
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.
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.
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.
Concluding Remarks • Product diversity via small changes in enyne • Atom economical • Recycleability of catalyst ( > 5 times) • 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.
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
Professor Richard Hsung 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 Kat Myhre Brittland DeKorver Hsung Group All of you for listening! Acknowledgements