Transcript
Page 1: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Ulm,

Page 2: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade
Page 3: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade
Page 4: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade
Page 5: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Pd catalysts

PdCl2(dppf)

Pd2dba3

Pd(PPh3)4

Page 6: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Negishi-coupling

Page 7: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Yong Yu, Andrew D. Bond, Philip W. Leonard, Ulrich J. Lorenz, Tatiana V. Timofeeva, K. Peter C. Vollhardt, Glenn D. Whitener and Andrey A. Yakovenko (2006). "Hexaferrocenylbenzene". Chem. Commun. (24): 2572–2574.

Page 8: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Negishi is better than Stille

Page 9: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade
Page 10: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

The ZACA-ReactionZirconium-catalyzed asymmetric carboalumination

Page 11: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade
Page 12: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Liang, B.; Negishi, Ei-ichi. Highly Efficient Asymmetric Synthesis of Fluvirucinine A1 via Zr-Catalyzed Asymmetric Carboalumination of Alkenes (ZACA)-Lipase-Catalyzed Acetylation Tandem Process. Org. Lett. 2008, 10(2),193-195.

Page 13: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade
Page 14: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade
Page 15: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Motuporin-dimethyl-diester

1,3-Dienes from Alkyne and Vinyliodide

Page 16: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Synthesis of linear terpenes

Review: Negishi,E.; Hu, Q.; Huang, Z.; Quian, M.; Wang, G. Aldrichimica Acta 2005, 38, 71.

Page 17: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade
Page 18: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Recent applications of the Suzuki–Miyaura cross-coupling reaction in organic synthesis Sambasivarao Kotha, Kakali Lahiri and Dhurke Kashinath Tetrahedron 2002, 48, 9633-9695

Suzuki-Miyaura-cross coupling

Page 19: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade
Page 20: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade
Page 21: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Synthesis of B2pin2

Page 22: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade
Page 23: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade
Page 24: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Pd[PPh3)]4

BBr3

Page 25: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Epothilones A (R =H= and B (R= Me)

Danishefsky, S. J. et al, Angew. Chem., Int. Ed. Eng. 1997, 36(7), 757-759

Page 26: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Stille CC Cross Coupling

Page 27: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Rate of ligand transfer (transmetalation) from tin:alkynyl > alkenyl > aryl > allyl = benzyl > α-alkoxyalkyl > alkyl

P. Espinet, A. M. Echavarren (2004). "The Mechanisms of the Stille Reaction". Angew. Chem. Int. Ed. 43 (36): 4704–4734.

Page 28: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Intramolecular Stille coupling

Page 29: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Kumada-Corriu Cross Coupling

Page 30: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

A Kumada coupling or Kumada-Corriu coupling is a cross coupling reaction in organic chemistry between an alkyl or aryl Grignard reagent and an aryl or vinyl halocarbon catalysed by nickel or palladium. This reaction is relevant to organic synthesis because it gives access to styrene derivatives. The reaction type was reported independently by two groups in 1972, and was named after Makoto Kumada. The reaction forshadowed many related metal-catalyzed coupling reactions, such as the Sonogashira coupling and the Suzuki coupling.

Page 31: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade
Page 32: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Buchwald-Hartwig CN-Coupling

Page 34: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Sonogashira-Castro-Reaction

Sonogashira, K.; Tohda, Y.; Hagahira, N. Tetrahedron Lett. 1975, 50, 4467

Page 35: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade
Page 36: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Heck Reaction

Is not a CC-coupling but olefin addition elimination process

Page 37: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Catalytic cycle of the Heck reaction

Page 38: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade
Page 39: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Stereo- and Regiochemistry

Page 40: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Formation of bridged rings

Page 41: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Bridged rings in natural products synthesis

Page 42: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Fused rings in natural products synthesis

Page 43: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Formation of spirocyclesby 6-exo-attack

Page 44: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Double spirocyclization

Page 45: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Bicyclic alkenes

Page 46: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Cyclizations onto acyclic alkenes

Page 47: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Axially chiral induction

Page 48: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Cascade cyclization

Page 49: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

6-exo-cyclization

Page 50: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Cascade reaction

Page 51: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Cyclizations onto exocyclic olefins: eclipsed boat transition state

Page 52: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

6-exo onto seven-membered ring

Page 53: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

6-exo with stereogenic center outside the tether

Page 54: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

7-exo cyclization

Page 55: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Asymmetric version

Page 56: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Chiral phosphines

Page 57: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Enantiotopos selectivity

Page 58: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Synthesis of polyketides

Page 59: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade
Page 60: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Alkaloids

Page 61: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade
Page 62: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Rhazinilam

Page 63: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Gu, Z.; Zakarian, A. Org. Lett. 2010,12, 4224-4227

Page 64: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

References Heck-reaction(1) (a) Mizoroki, T.; Mori, K.; Ozaki, A. Bull. Chem. Soc. Jpn. 1971,44, 581. (b) Heck, R. F.; Nolley, J. P., Jr. J. Org. Chem. 1972,37, 2320.(2) Selected reviews include: (a) de Meijere, A.; Meyer, F. E. Angew.Chem., Int. Ed. Engl. 1994, 33, 2379. (b) Bräse, S.; de Meijere,A. In Metal-Catalyzed Cross Coupling Reactions; Stang, P. J.,Diederick, F., Eds; Wiley-VCH: Weinheim, 1998; Chapter 3. (c)Link, J. T.; Overman, L. E. In Metal-Catalyzed Cross CouplingReactions; Stang, P. J., Diederick, F., Eds; Wiley-VCH: Weinheim,1998; Chapter 6. (d) Link, J. T. Organic Reactions; Wiley:Hoboken, NJ, 2002; Vol. 60, Chapter 2.(3) For recent reviews of the asymmetric Heck reaction, see: (a)Shibasaki, M.; Vogl, E. M. J. Organomet. Chem. 1999, 1. (b)Donde, Y.; Overman, L. E. In Catalytic Asymmetric Synthesis;Ojima, I., Ed.; Wiley-VCH: New York, 2000; Chapter 8G.(4) Dounay, A. B.; Overman, L. E. Chem. Rev. 2003, 103, 2945.

Page 65: Ulm, - univie.ac.atmulzer.univie.ac.at/fileadmin/user_upload/ag_rg_mulzer/...Cyclizations onto acyclic alkenes Axially chiral induction Cascade cyclization 6-exo-cyclization Cascade

Carbocyclization with Pd


Recommended