Abstract: We report a versatile, highly enantioselective intramolecular hydroarylation of allenyl-tethered pyrroles and indoles. The reaction, promoted by an iridium(I)/bisphosphine chiral catalyst, provides a direct access heteropolycyclic systems bearing either tertiary or quaternary carbon stereocenters and a synthetically appealing alkenyl pendant. The method allows a highly efficient assembly of five-, six- and even seven-membered fused indole and pyrrole products, providing enantiomeric excesses of up to 99%. DFT computational studies align nicely with the experimental results and allow to rationalize the key factors that control both regio- and stereoselectivity of the process. Finally, the synthetic potential of the method was exemplified with a very short, highly enantioselective formal synthesis of (+)-Rhazinilam

External link: https://onlinelibrary.wiley.com/doi/10.1002/anie.202508252

Abstract: The discovery and development of artificial catalysts to carry out bioorthogonal reactions in living cells is a primary goal at the interface of Chemistry and Biology. Current approaches rely on time-consuming trial-and-error methods. As an alternative, we show that positionally addressable combinatorial libraries (SPOT libraries) provide a significant advantage for the efficient identification of novel catalytic metallopeptides. Using these libraries, we were able to rapidly identify catalytic β-hairpin palladopeptides capable of promoting efficient depropargylation reactions in challenging intracellular environments.

External link: https://pubs.acs.org/doi/10.1021/acscatal.5c00525

We are really pleased to announce here that our research article at ACS Catal., entitled "Bis-CF3-bipyridine Ligands for the Iridium-Catalyzed Borylation of N-Methylamides" and authored by D. Marcos-Atanes, G. Jiménez-Osés and J. L. Mascareñas has been accepted and it's already on-line.

Abstract: Bipyridine and phenanthroline are well-established neutral ligands for promoting iridium-catalyzed borylations of aromatic C–H bonds. However, their use with aliphatic substrates is almost uncharted. Herein we demonstrate that introducing CF substituents at the 5- and 5′-positions of bipyridine generates ligands that enable an efficient and regioselective iridium-catalyzed borylation of the methyl group in a broad variety of methylamides. The reaction shows broad functional group tolerance and exhibits remarkable selectivity, offering a powerful approach for the borylation of challenging aliphatic C–H bonds. Mechanistic investigations, including computational analysis, suggest that the accelerating effect of the ligand is likely associated with the formation of non-covalent dispersion interactions between the carbonyl amide of the substrates and the trifluoromethylated pyridine rings of the ligand.

External link: https://pubs.acs.org/doi/full/10.1021/acscatal.5c00933