by Jeremy ZIMBRON

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

2. Cyclopentadienyl ligands (Cp) • Common anionic ancillary ligand in organometallic chemistry • Ferrocene is the classic cyclopentadienyl compound • Discovered and identified by Woodward, Wilkinson and Fischer in the • 1950s1 Wilkinson and Fischer dancing at the final reception of the Conference on Organometallic Chemistry in July 1974 in Ettal • Tigger important developments in modern organometallic chemistry • H. Werner, Angew. Chem. Int. Ed. 2012, 51, 6052-6058.

3. Cyclopentadienyl ligands (Cp) • Present in some of the most active catalysts: Stereospecific olefin polymerization2 Enantioselective C-C and C-H Bond Formation5 Hydroxylation of alkanes6 Hydroacylation of olefins with aromatic aldehydes4 Enantioselective Diels-Alder3 • H. Werner, Angew. Chem. Int. Ed. 2012, 51, 6052-6058. • Waymouth et al., Angew. Chem. Int. Ed. 1995, 34, 1143-1170. • F. Viton, G. Bernardinelli and E. P. Kündig, J. Am. Chem. Soc., 2002, 124, 4968 • A. D. Bolig, M. Brookhart, J. Am. Chem. Soc. 2007, 129, 14544. • A. H. Hoveyda, J. P. Morken, Angew. Chem. Int. Ed. Engl. 1996, 35, 1262. • M. Zhou, N. D. Schley, R. H. Crabtree, J. Am. Chem. Soc. 2010, 132, 12550.

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.,Organometallics2004, 23, 1002-1009.

5. Designing chiral Cp metal complexes1 • Cyclopentadienyl-derived chirality • Metal-centered chirality • Combined metal-centered • and Cp-derived chirality • Mono-bidentate chiral ligands 1. R. L. Halterman. Chem. Rev. 1992, 92, 965-994.

6. Designing chiral Cp metal complexes1 • Cyclopentadienyl-derived chirality • Metal-centered chirality • Combined metal-centered • and Cp-derived chirality No C2 symmetry in chiral Cp ligands: form diastereomers during coordination of the metal Separate diastereomeric complexes 1. R. L. Halterman. Chem. Rev. 1992, 92, 965-994.

7. Designing chiral Cp ligand Ligand features to achieve the required selectivity: • 1,2-substituted cyclopentadiene with C2-symmetric Cp derivatives Provides one chiral complex

8. Designing chiral Cp ligand Ligand features to achieve the required selectivity: • 1,2-substituted cyclopentadiene with C2-symmetric Cp derivatives • Restriction of rotation around the Cp moiety: a single preferential alignment of substrates

9. Designing chiral Cp ligand Ligand features to achieve the required selectivity: • 1,2-substituted cyclopentadiene with C2-symmetric Cp derivatives • 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. Structure of chiral Cpx*Rh(I) complexes • Different backside shielding from the corresponding C2-symmetric Cp precursors • Relatively air-stable and easy to handle

11. Synthesis of chiral Cpx*Rh(I) complexes • Synthesis of the C2-symmetric cyclopentadienes 13 15-crown-5, THF 54%

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

13. C–H bond functionalization using Rh catalysts1 • Cramer: enantioselective [3+2] cycloaddition2 DTBM-MeOBiphep imine directing group • G. Song, F. Wang, X. Li, Chem. Soc. Rev. 2012, 41, 3651-3678. • D. N. Tran, N. Cramer, Angew. Chem. Int. Ed. 2011, 50, 11098-11102.

14. C–H bond functionalization using Rh catalysts1 • Cramer: enantioselective [3+2] cycloaddition2 • C-H functionalization using an oxidizing directing group3,4 • Glorius work3 • Fagnou work4 • Excellent directing group • Internal oxidant • Mild conditions • High functional group • compatibility • G. Song, F. Wang, X. Li, Chem. Soc. Rev. 2012, 41, 3651-3678. • D. N. Tran, N. Cramer, Angew. Chem. Int. Ed. 2011, 50, 11098-11102. • S. Rakshit, C. Grohmann, T. Besset, F. Glorius, J. Am. Chem. Soc. 2011, 133, 2350-2353. • N. Guimond, S. I. Gorelsky, K. Fagnou, J. Am. Chem. Soc. 2011, 133, 6449-6457.

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

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

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

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

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

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

21. Substrate scope: olefin acceptors

22. Substrate scope: aryl hydroxamates

23. Presumed catalytic cycle for the cyclization

24. Postulated model for the stereochemical preference

25. Presumed catalytic cycle for the cyclization

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. Presumed catalytic cycle for the cyclization

28. Conclusion • A class of chiral Cpx* 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. 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

32. Oxidizing Directing Groups in CH Activation Reactions • Cui and Wu previous work1 Quinoline N-oxides: directing group and internal oxidant • Fagnou previous work2 Benzhydroxamic acid: directing group and internal oxidant • J. Wu, X. Cui, L. Chen, G. Jiang, Y. Wu, J. Am. Chem. Soc. 2009, 131, 13888. • N. Guimond, C. Gouliaras, K. Fagnou, J. Am. Chem. Soc. 2010, 132, 6908