External link: https://pubs.acs.org/doi/10.1021/acs.orglett.6c01113

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