1. by Jeremy ZIMBRON Literature Meeting November 27 th, 2012

2. 2 Cyclopentadienyl ligands (Cp) 1.H. Werner, Angew. Chem. Int. Ed. 2012, 51, 6052-6058. Common anionic ancillary ligand in organometallic chemistry Ferrocene is the classic cyclopentadienyl compound Discovered and identified by Woodward, Wilkinson and Fischer in the 1950s 1 Tigger important developments in modern organometallic chemistry Wilkinson and Fischer dancing at the final reception of the Conference on Organometallic Chemistry in July 1974 in Ettal

3. 3 Cyclopentadienyl ligands (Cp) 1.H. Werner, Angew. Chem. Int. Ed. 2012, 51, 6052-6058. 2.Waymouth et al., Angew. Chem. Int. Ed. 1995, 34, 1143-1170. 3.F. Viton, G. Bernardinelli and E. P. Kündig, J. Am. Chem. Soc., 2002, 124, 4968 4.A. D. Bolig, M. Brookhart, J. Am. Chem. Soc. 2007, 129, 14544. 5.A. H. Hoveyda, J. P. Morken, Angew. Chem. Int. Ed. Engl. 1996, 35, 1262. 6.M. Zhou, N. D. Schley, R. H. Crabtree, J. Am. Chem. Soc. 2010, 132, 12550. Present in some of the most active catalysts: Stereospecific olefin polymerization 2 Enantioselective Diels-Alder 3 Hydroacylation of olefins with aromatic aldehydes 4 Enantioselective C-C and C-H Bond Formation 5 Hydroxylation of alkanes 6

4. 4 About Cp and Cp* ligands Inert to both nucleophilic or electrophilic reagents Strong binding to metal centers Large array of possible structural modifications of the ligand In asymmetric catalysis Cp ligands have been bypassed by chiral ligands Only few examples of chiral Cp inducing enantioselection A. Gutnov et al., Angew. Chem. Int. Ed. 2004, 43, 3795 and A. Gutnov et al., Organometallics 2004, 23, 1002-1009.

5. 5 Designing chiral Cp metal complexes 1 1. R. L. Halterman. Chem. Rev. 1992, 92, 965-994. Cyclopentadienyl-derived chirality Metal-centered chirality Combined metal-centered and Cp-derived chirality Mono-bidentate chiral ligands

6. 6 Designing chiral Cp metal complexes 1 1. R. L. Halterman. Chem. Rev. 1992, 92, 965-994. Cyclopentadienyl-derived chirality Metal-centered chirality Combined metal-centered and Cp-derived chirality No C 2 symmetry in chiral Cp ligands: form diastereomers during coordination of the metal Separate diastereomeric complexes

7. 7 1,2-substituted cyclopentadiene with C 2 -symmetric Cp derivatives Ligand features to achieve the required selectivity: Provides one chiral complex Designing chiral Cp ligand

8. 8 1,2-substituted cyclopentadiene with C 2 -symmetric Cp derivatives Ligand features to achieve the required selectivity: Designing chiral Cp ligand Restriction of rotation around the Cp moiety: a single preferential alignment of substrates

9. 9 1,2-substituted cyclopentadiene with C 2 -symmetric Cp derivatives Ligand features to achieve the required selectivity: Designing chiral Cp ligand Restriction of rotation around the Cp moiety: a single preferential alignment of substrates A shield from a remote substituent: direct the approach of the incoming reactant

10. 10 Structure of chiral Cpx*Rh(I) complexes Different backside shielding from the corresponding C 2 -symmetric Cp precursors Relatively air-stable and easy to handle

11. 11 Synthesis of chiral Cpx*Rh(I) complexes Synthesis of the C 2 -symmetric cyclopentadienes 13 15-crown-5, THF 54%

12. 12 Synthesis of chiral Cpx*Rh(I) complexes

13. 13 C–H bond functionalization using Rh catalysts 1 1.G. Song, F. Wang, X. Li, Chem. Soc. Rev. 2012, 41, 3651-3678. 2.D. N. Tran, N. Cramer, Angew. Chem. Int. Ed. 2011, 50, 11098-11102. Cramer: enantioselective [3+2] cycloaddition 2 imine directing group DTBM-MeOBiphep

14. 14 C–H bond functionalization using Rh catalysts 1 1.G. Song, F. Wang, X. Li, Chem. Soc. Rev. 2012, 41, 3651-3678. 2.D. N. Tran, N. Cramer, Angew. Chem. Int. Ed. 2011, 50, 11098-11102. 3.S. Rakshit, C. Grohmann, T. Besset, F. Glorius, J. Am. Chem. Soc. 2011, 133, 2350-2353. 4.N. Guimond, S. I. Gorelsky, K. Fagnou, J. Am. Chem. Soc. 2011, 133, 6449-6457. Cramer: enantioselective [3+2] cycloaddition 2 C-H functionalization using an oxidizing directing group 3,4 Glorius work 3 Fagnou work 4 Excellent directing group Internal oxidant Mild conditions High functional group compatibility

15. 15 Optimization of the asymmetric C-H functionalization R R

16. 16 Optimization of the asymmetric C-H functionalization R R

17. 17 Optimization of the asymmetric C-H functionalization R R

18. 18 Optimization of the asymmetric C-H functionalization R R

19. 19 Optimization of the asymmetric C-H functionalization R R

20. 20 Substrate scope: olefin acceptors Variety of styrenes are competent reaction partners

21. 21 Substrate scope: olefin acceptors

22. 22 Substrate scope: aryl hydroxamates

23. 23 Presumed catalytic cycle for the cyclization

24. 24 Postulated model for the stereochemical preference

25. 25 Presumed catalytic cycle for the cyclization

26. 26 Presumed catalytic cycle for the cyclization 7-membered rhodacycle is stabilized with the extra coordination of the carbonyl oxygen of BOC L. Xu, Q. Zhu, G. Huang, B. Cheng, Y. Xia, J. Org. Chem. 2012, 77, 3017.

27. 27 Presumed catalytic cycle for the cyclization

28. 28 Conclusion A class of chiral Cp x* analogs with low molecular weight Desymmetrize a Rh(III)-catalyzed directed C–H bond functionalization Reaction proceeds under mild conditions and is high yielding and enantioselective Unlock the potential of chiral Cp ligands in enantioselective catalysis with half-sandwich complexes Asymmetric catalytic amination of alcohols R. Kawahara, K-i. Fujita, R. Yamaguchi, Adv. Synth. Catal. 2011, 353, 1161–1168.

29. 29 How to induce chirality with Cp complexes? Coordination of chiral ligands: diamines or phosphines Chiral, non racemic cyclopentadienyl ligands Biochemical approach: Cp-complex embedded into a chiral protein environment Biotinylated Cp complex Sav protein

30. 30

31. 31

32. 32 Oxidizing Directing Groups in CH Activation Reactions Cui and Wu previous work 1 1.J. Wu, X. Cui, L. Chen, G. Jiang, Y. Wu, J. Am. Chem. Soc. 2009, 131, 13888. 2.N. Guimond, C. Gouliaras, K. Fagnou, J. Am. Chem. Soc. 2010, 132, 6908 Fagnou previous work 2 Quinoline N-oxides: directing group and internal oxidant Benzhydroxamic acid: directing group and internal oxidant