RESUMO
p-Toluenesulfonyl (Tosyl) and nitrobenzenesulfonyl (Nosyl) are two of the most common sulfonyl protecting groups for amines in contemporary organic synthesis. While p-toluenesulfonamides are known for their high stability/robustness, their use in multistep synthesis is plagued by difficult removal. Nitrobenzenesulfonamides, on the other hand, are easily cleaved but display limited stability to various reaction conditions. In an effort to resolve this predicament, we herein present a new sulfonamide protecting group, which we term Nms. Initially developed through in silico studies, Nms-amides overcome these previous limitations and leave no room for compromise. We have investigated the incorporation, robustness and cleavability of this group and found it to be superior to traditional sulfonamide protecting groups in a broad range of case studies.
RESUMO
A new generation of chiral gold(I) catalysts based on variations of complexes with JohnPhos-type ligands with a remote C2-symmetric 2,5-diarylpyrrolidine have been synthesized with different substitutions at the top and bottom aryl rings: from replacing the phosphine by a N-heterocyclic carbene (NHC) to increasing the steric hindrance with bis- or tris-biphenylphosphine scaffolds, or by directly attaching the C2-chiral pyrrolidine in the ortho-position of the dialkylphenyl phosphine. The new chiral gold(I) catalysts have been tested in the intramolecular [4+2] cycloaddition of arylalkynes with alkenes and in the atroposelective synthesis of 2-arylindoles. Interestingly, simpler catalysts with the C2-chiral pyrrolidine in the ortho-position of the dialkylphenyl phosphine led to the formation of opposite enantiomers. The chiral binding pockets of the new catalysts have been analyzed by DFT calculations. As revealed by non-covalent interaction plots, attractive non-covalent interactions between substrates and catalysts direct specific enantioselective folding. Furthermore, we have introduced the open-source tool NEST, specifically designed to account for steric effects in cylindrical-shaped complexes, which allows predicting experimental enantioselectivities in our systems.
