Modern Synthetic Methods Dr. Dorian Didier dodich@cup.uni-muenchen.de
Functionnalized Organometallic Reagents C-N, C-O and C-S Bond Formation Introduction to Organoboron Chemistry Introduction to Organosilicon Chemistry Carbometallation Reactions
Functionnalized Organometallic Reagents C-N, C-O and C-S Bond Formation Introduction to Organoboron Chemistry Introduction to Organosilicon Chemistry Carbometallation Reactions
Generalities Suzuki-Miyaura with R-BF 3 K Reagents Stille Negishi Corriu-Kumada-Tamao Sonogashira Heck Arylation of Enolates
Generalities 4
Generalities I >> Br > OTf > Cl Very slow Slow Fast Fast Very slow 5
Suzuki-Miyaura High tolerance of functionnal grougs T. Heh et al. Tetrahedron Lett. 2005, 46, 3573. 6
Suzuki-Miyaura A. E. Thompson et al. J. Org. Chem. 2005, 70, 388. M. Uesugi et al. J. Am. Chem. Soc. 2009, 131, 4774. 7
Suzuki-Miyaura C. M. Crudden et al. J. Am. Chem. Soc. 2009, 131, 5024. Works with hindered substrates S. L. Buchwald et al. J. Am. Chem. Soc. 2005, 127, 4685 8
Suzuki-Miyaura Iterative M. D. Burke et al. J. Am. Chem. Soc. 2007, 129, 6716. J. Am. Chem. Soc. 2009, 131, 6961. 9
Suzuki-Miyaura Iterative M. Suginome et al. J. Am. Chem. Soc. 2007, 129, 758. Org. Lett. 2008, 10, 377. Org. Lett. 2009, 11, 1899.
Suzuki-Miyaura Better Understanding of the Mechanism 11
Suzuki-Miyaura Better Understanding of the Mechanism Oxidative Addition Csp 3 -X usually slow Favoured by Electronically Rich Ligands Bulky Ligands Can lead to b-h elimination
Suzuki-Miyaura Better Understanding of the Mechanism G. A. Molander Angew. Chem. Int. Ed. 2009, 48, 9240. J. A. Soderquist J. Org. Chem. 1998, 63, 461. Y. Kishi J. Am. Chem. Soc. 1987, 109, 4756. TM is accelerated by a base 13
Suzuki-Miyaura Better Understanding of the Mechanism Avoiding b-h Elimination Bulky Ligands Chelating Ligands 14
with R-BF 3 K Reagents G. Molander et al. J. Org. Chem. 2005, 70, 3950. G. Molander et al. J. Org. Chem. 2002, 67, 8416. 15
with R-BF 3 K Reagents G. A. Molander et al. J. Am. Chem. Soc. 2008, 130, 9257. G. A. Molander et al. J. Org. Chem. 2008, 73, 7481
with R-BF 3 K Reagents Mechanism G. A. Molander et al. J. Am. Chem. Soc. 2010, 132, 17108. 16
Overview of Different (pre)catalytic Systems and Common Ligands 17
Stille On the Mechanism P. Espinet et al. J. Am. Chem. Soc. 1998, 120, 8978. J. Am. Chem. Soc. 2000, 122, 11771. J. F. Hartwig et al. J. Am. Chem. Soc. 2001, 123, 1232. G.C. Fu et al. Angew. Chem. Int. Ed. 1999, 38, 2411. G.C. Fu et al. J. Am Chem. Soc. 2003, 125, 3718. 18
Stille E. J. Corey et al. J. Am. Chem. Soc. 1999, 121, 7600. G. Guillaumet et al. Org. Lett. 2003, 5, 803. L. S. Liebeskind et al. Org. Lett. 2003, 5, 801. 19
Negishi High Tolerance of Functionnal Groups P. Knochel et al. Org. Lett. 2005, 7, 4871. 20
Negishi «Quinoxaline» S. L. Buchwald et al. J. Am. Chem. Soc. 2004, 126, 13028. G. C. Fu et al. J. Am. Chem. Soc. 2001, 123, 2719. 21
Negishi Alkenyl-Zinc G. C. Fu et al. J. Am. Chem. Soc. 2001, 123, 2719. J. Am. Chem. Soc. 2002, 124, 6343. Alkyl-Zinc M. G. Organ et al. J. Org. Chem. 2005, 70, 8503. Org. Lett. 2005, 7, 3805. 22
Negishi Alkynyl-Zinc E. Negishi et al. Org. Lett 2003, 5, 1597. J. A. Miller et al. Tetrahedron Lett. 2004, 45, 4989. Tetrahedron Lett. 2005, 46, 2927. Org. Lett 2001, 3, 3111. (benzylic electrophiles) (aryl electrophiles) 23
Negishi Compatibility P. Knochel et al. Org. Lett. 2008, 10, 2765. P. Knochel et al. Chem. Eur. J. 2009,15, 1324. 24
Corriu-Kumada-Tamao S. Buchwald et al. J. Am. Chem. Soc. 2007, 129, 3844. 25
Corriu-Kumada-Tamao Ph-MgBr With -Cl and -F W. A. Herrmann et al. Angew. Chem. Int. Ed. 2000, 39, 1602. E. Nakamura et al. J. Am. Chem. Soc. 2005, 127, 17979. 26
Corriu-Kumada-Tamao Preparation Acceleration Effect Same observation in the presence of : P. Knochel Angew. Chem. Int. Ed. 2009, 48, 205. 27
Corriu-Kumada-Tamao 28
Corriu-Kumada-Tamao 29
Corriu-Kumada-Tamao Mechanism? Radicals? 30
Corriu-Kumada-Tamao Initiation Propagation 31
Corriu-Kumada-Tamao Variation of Electrophiles J. A. Miller et al. Tetrahedron Lett. 2001, 42, 6991. J. W. Dankwardt Angew. Chem. Int. Ed. 2004, 43, 2428. V. Snieckus et al. Angew. Chem. Int. Ed. 2004, 43, 888. 32
Corriu-Kumada-Tamao Copper-Catalyzed CKT Cross-Coupling N. Kambe et al. Angew. Chem. Int. Ed. 2007, 46, 2086. 33
Corriu-Kumada-Tamao Copper-Catalyzed CKT Cross-Coupling MgCl MgCl N. Kambe et al. Angew. Chem. Int. Ed. 2007, 46, 2086. 34
Corriu-Kumada-Tamao Copper-Catalyzed CKT Cross-Coupling N. Kambe et al. Angew. Chem. Int. Ed. 2007, 46, 2086. 35
Corriu-Kumada-Tamao Copper-Catalyzed CKT Cross-Coupling N. Kambe et al. Angew. Chem. Int. Ed. 2007, 46, 2086. 36
Corriu-Kumada-Tamao Manganese-Catalyzed CKT Cross-Coupling Stereoretention G. Cahiez et al. Org. Lett. 2008, 10, 5255. 37
Corriu-Kumada-Tamao Silver-Catalyzed CKT Cross-Coupling Specially on Bulky Electrophiles K. Oshima Org. Lett. 2008, 10, 969. 38
Corriu-Kumada-Tamao Special Case of N-tosylhydrazones P. Aznar et al. Angew. Chem. Int. Ed. 2007, 46, 5587. 39
Corriu-Kumada-Tamao Special Case of N-tosylhydrazones 40
Corriu-Kumada-Tamao Special Case of N-tosylhydrazones 41
Sonogashira From terminal alkynes Can be catalyzed by few transition metal complexes 42
Sonogashira 43
Sonogashira S. L. Buchwald et al. Org.Lett. 2000, 2, 1729. C.-G. Cho et al. Org. Lett. 2002, 4, 1171. 44
Sonogashira Copper-Catalyzed, Paladium-Free M. Taillefer et al. Org. Lett. 2008, 10, 3203. 45
Sonogashira M. Taillefer et al. Org. Lett. 2008, 10, 3203. 46
Sonogashira Iron-Catalyzed M. Nakamura et al. Angew. Chem. Int. Ed. 2011, 50, 10973. 47
Heck 48
Heck G. C. Fu et al. J. Org. Chem. 1999, 64, 10. I. Beletskaya et al. Chem. Rev. 2000, 100, 3009. (review) 49
Heck S. Cacchi et al. Org. Lett. 2003, 5, 777. T. Tu et al. Synlett, 2011, 951. 50
Heck M. Santelli et al. Synthesis 2008, 1142. T. Skydstrup et al. Angew. Chem. Int. Ed. 2006, 45, 3349. 51
Heck M. Santelli, Synthesis, 2006, 3495 J. Xiao, Angew. Chem. Int. Ed., 2006, 45, 4152 52
Heck regioselectivities? 53
Heck J. Zhou et al. J. Am. Chem. Soc. 2014, 136, 650. 54
Heck Decarboxylative Heck A. G. Myers et al. J. Am. Chem. Soc. 2002, 124, 11250. 55
Heck Decarboxylative Heck A. G. Myers et al. Org. Lett. 2004, 6, 433. 56
Arylation of Enolates 57
Arylation of Enolates J. F. Hartwig et al. J. Org. Chem. 1998, 63, 6546. Lloyd-Jones et al. Angew. Chem. Int. Ed. 2002, 41, 953. 58
Arylation of Enolates S. L. Buchwald et al. J. Am. Chem. Soc. 2000, 122, 1360. J. F. Hartwig et al.j. Am. Chem. Soc. 2002, 124, 9330. S. L. Buchwald et al. J. Org. Chem. 2002, 67, 106. 59
Arylation of Enolates J. F. Hartwig et al. J. Am. Chem. Soc. 2005, 127, 15824. 60
Arylation of Enolates F. Y. Kwong et al. Org. Lett. 2007, 9, 3469. 61
Arylation of Enolates Remote Arylation J. F. Hartwig et al. Angew. Chem. Int. Ed. 2010, 49, 5757. P. Knochel et al. Org. Lett. 2011, 13, 1690. 62