Enantioselective Catalysis with 3d Transition Metal Complexes: Chiral Pincers as Stereodirecting Ligands

Meridionally coordinating chiral tridentate ligands, frequently referred to as “pincers”,[1] provide the structural platform for the construction of efficient stereodirecting molecular environments. Whilst many of the known chiral systems of the “pincer” type perform relatively poorly in enantioselective catalysis due to certain lack of control of substrate orientation, their assembly from rigid heterocyclic units recently has given rise to several highly enantioselective catalysts[2] which have been proven to be efficient in a variety of applications in organic synthesis.

During the past decade, we developed chiral bis(oxazolinylmethyl)pyrroles[3] as well as bis(pyridylimino)isoindole (bpi) derivatives which have been used as stereodirecting ligands inter alia in Fe-catalyzed enantioselective hydrosilylations of ketones, Co-catalyzed cyclopropanations[4] and Ni-catalyzed hydrodehalogenations of prochiral geminal dihalides.[5]

More recently, we developed bis(oxazolinylmethylidene)isoindoline (“Boxmi”) ligands [6] which have been used in a variety of enantioselective transformations including alkylations of β-ketoesters and their subsequent cyclization to spirolactones,[6b] as well as the trifluoromethylation, trifluoromethylthiolation[6c,e] and azidation of β-ketoesters and oxindoles.[6d]

[1] Reviews covering “pincer” complex chemistry: a) M. Albrecht, G. van Koten, Angew. Chem., Int. Ed. 2001, 40, 3750; b) M. van der Boom, D. Milstein, Chem. Rev. 2003, 103, 1759. See also: Organometallic Pincer Chemistry. Topics in Organometallic Chemistry. (Ed. van Koten, G.; Milstein. D.), 2013, 40, Springer, New York.

[2] a) Comprehensive Asymmetric Catalysis (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer, Berlin, 1999; b) New Frontiers in Asymmetric Catalysis, (Eds.: K. Mikami, M. Lautens), Wiley: Hoboken, NJ, 2007; c) Catalysis in Asymmetric Synthesis, 2nd ed. (Eds.: V. Caprio, J. M. J. Williams), Wiley: Hoboken, NJ, 2009; d) Catalytic Asymmetric Synthesis, 3rd ed. (Ed.: I. Ojima), Wiley: Hoboken, NJ, 2010.

[3] a) C. Mazet, L. H. Gade, Chem. Eur. J. 2003, 9, 1759; b) F. Konrad, J. Lloret Fillol, H. Wadepohl, L. H. Gade, Inorg. Chem. 2009, 48, 8523.

[4] B. K. Langlotz, H. Wadepohl, L. H. Gade, Angew. Chem. Int. Ed. 2008, 47, 4670.

[5] C. Rettenmeier, H. Wadepohl, L. H. Gade, Chem. Eur. J. 2014, 20, 9657.

[6] a) Q.-H. Deng, H. Wadepohl, L. H. Gade, Chem. Eur. J. 2011, 17, 14922; b) Q.-H. Deng, H. Wadepohl, L. H. Gade, J. Am. Chem. Soc. 2012, 134, 2946; c) Q.-H. Deng, H. Wadepohl, L. H. Gade, J. Am. Chem. Soc. 2012, 134, 10769; d) Q.-H. Deng, T. Bleith, H. Wadepohl, L. H. Gade, J. Am. Chem. Soc. 2013, 135, 5356; e) Q.-H. Deng, C. Rettenmeier, H. Wadepohl, L. H. Gade, Chem. Eur. J. 2014, 20, 93.