Compared with peripheral late-stage transformations mainly focusing on carbon–hydrogen functionalizations, reliable strategies to directly edit the core skeleton of pharmaceutical lead compounds still remain scarce despite the recent flurry of activity in this area. Herein, we report the skeletal editing of indoles through nitrogen atom insertion, accessing the corresponding quinazoline or quinoxaline bioisosteres by trapping of an electrophilic nitrene species generated from ammonium carbamate and hypervalent iodine. This reactivity relies on the strategic use of a silyl group as a labile protecting group that can facilitate subsequent product release. The utility of this highly functional group-compatible methodology in the context of late-stage skeletal editing of several commercial drugs is demonstrated.

We report a convenient protocol for a nitrogen atom insertion into indenes to afford isoquinolines. The strategy further enables the synthesis of pyridines from cyclopentadienes and a facile access to 15N labelled isoquinolines.

The nucleus‐independent chemical shift (NICS)‐XY‐Scan is a simple and easy tool for the quantitative measurement of the aromaticity of polycyclic aromatic hydrocarbons and identification of the existence of local and global ring currents. We recently introduced an additivity scheme that uses the NICS‐XY‐Scans of smaller building blocks to predict the aromatic profiles of larger polycyclic aromatic hydrocarbon systems. We now report on an expansion of the methodology to include systems of varying aromatic natures containing the heteroatoms B, N, O, and S. The additivity approach allows for rapid and resource‐efficient generation of NICS‐XY‐Scans of large, complex systems. Moreover, it reveals that the magnetic criterion of aromaticity behaves in an additive manner, and that the ring currents of multi‐ring systems appear to be mostly localized within subunits of up to three rings.

The past 20 years have seen an extensive implementation of nickel in homogeneous catalysis through the development of unique reactivity not easily achievable by using noble transition metals. Many catalytic cycles propose Ni­(I) complexes as potential reactive intermediates, yet the scarcity of nickel­(I) precursors and the lack of a general, non-ligand-specific protocol for their synthesis have hampered progress in this field of research. This has in turn also limited the access to novel, well-defined Ni­(I) species for the development of new catalytic reactions. Herein, we report a simple, general route to access a wide variety of Ni­(I)–phenolate complexes via an unusual example of an olefinic Ni­(I) complex, [Ni­(COD)­(OPh*)] (COD = 1,5-cyclooctadiene, OPh* = O­( t Bu)3C6H2). This route has proven to be highly efficient for several coordination numbers and ligand classes enabling access to the following complexes: [Ni­(IPr)­(OPh*)] (IPr = 1,3-bis­(2,6-diisopropyl­phenyl)­imidazol-2-ylidene), [Ni­(dcype)­(OPh*)] (dcype = 1,2-bis­(dicyclohexyl­phosphino)­ethane), [Ni­(dppe)­(OPh*)] (dppe = 1,2-bis­(diphenyl­phosphino)­ethane), and [Ni­(terpy)­(OPh*)] (terpy = 2,2′:6′,2″-terpyridine). Moreover, reacting [Ni­(dcype)­(OPh*)] with trimethylsilyl triflate has led to the isolation of a unique example of a cationic binuclear Ni­(I)–arene complex. All these complexes have been characterized by single-crystal X-ray, DFT, and EPR analyses, thus providing crucial experimental and theoretical information about their coordination environment and confirming a d9 electronic structure for all complexes involved. Overall, this new synthetic approach offers exciting opportunities for the discovery of new stoichiometric and catalytic reactivity as well as the mechanistic elucidation of Ni-based catalytic cycles.

In the last twenty years, nickel has successfully imprinted its role in the field of homogeneous catalysis as a valid and complementary alternative to palladium and platinum catalysts. However, compared to those, there are often many different available pathways in nickel catalysis due to the facile access of intermediate oxidation states. Among them, Ni(I) has been increasingly proposed as a key oxidation state in multiple transformations. This oxidation state had already been suggested a long time ago but has only recently undergone a renaissance with extensive ligand design which has led to over 100 isolated Ni(I) complexes. In addition, the analysis of many catalytic cycles has revealed that the Ni(I) species can not only occur as a decomposition product perturbing a Ni(0) -Ni(II) pathway but can also play a key role in alternative Ni(I)-Ni(III) cycles. This behavior is highly dependent on the class of transformation and ligand employed in catalysis. Herein, we concisely describe the journey of this oxidation state, combining the information gathered from inorganic synthesis and mechanistic investigations, from its synthesis to its postulated role in different catalytic cycles.