Iridium at the Controls: Steering Selectivity toward Molecular Complexity

The development of transition-metal-catalyzed C–C and C–N bond-forming methods that enable the efficient and stereoselective construction of valuable chiral skeletons remains a highly active research area, with ample opportunities for significant advances.
In particular, efficient approaches based on the metal-catalyzed direct addition of C–H and N–H bonds across unsaturated systems (i.e., hydrocarbonation and hydroamination reactions) are very attractive because of their overall atom economy and the structural simplicity of the required precursors.1 Despite major advances over the past decades, this field is far from mature, and there is a particular need for new methods that offer excellent control over chemo-, regio-, and enantioselectivity, enabling access to products bearing highly challenging tetrasubstituted stereocenters and/or multiple stereocenters in a fully stereoselective manner.
In this context, I will summarize our recent efforts to harness the distinctive reactivity of iridium catalysts to promote asymmetric hydrocarbonation and hydroamination reactions with unconventional selectivities in both intra- and intermolecular settings. The application of one of these processes to natural product synthesis will also be highlighted.2

1 a) R. Blieck, M. Taillefer, F. Monnier, Chem. Rev. 2020, 120, 13545-13598. b) C. G. Newton, S. G. Wang, C. C. Oliveira, N. Cramer, Chem. Rev. 2017, 117, 8908-8976. c) S. Ma, J. F. Hartwig, Acc. Chem. Res. 2023, 56, 1565-1577.
2 a) A. Arribas, M. Calvelo, D. F. Fernández, C. A. B. Rodrigues, J. L. Mascareñas, F. López, Angew. Chem. Int. Ed. 2021, 60, 19297. b) A. Arribas, M. Calvelo, A. Rey, J. L. Mascareñas, F. López, Angew. Chem. Int. Ed. 2024, 63, e202408258. c) A. Rey, A. Arribas, J. L. Mascareñas, F. López, Angew. Chem. Int. Ed. 2025, 64, e202512027. d) A. Arribas, A. Rey, M. Calvelo, J. L. Mascarenas, F. López, Angew. Chem. Int. Ed. 2025, e202508252.