RESUMO
Previous studies by Desiraju and co-workers have implicated the acidic hydrogen atoms of cubane as a support network for hydrogen bonding groups. Herein we report a detailed structural analysis of all currently available 1,4-disubstituted cubane structures with an emphasis on how the cubane scaffold interacts in its solid-state environment. In this regard, the interactions between the cubane hydrogen atoms and acids, ester, halogens, ethynyl, nitrogenous groups, and other cubane scaffolds were cataloged. The goal of this study was to investigate the potential of cubane as a substitute for phenyl. This could be achieved by analyzing all contacts that are directed by the cubane hydrogen atoms in the X-ray crystal structures. As a result, we have established several new cubane interaction profiles, such as the catemer formation seen in esters, the preferences of halogen-hydrogen contacts over direct halogen bonding, and the stabilizing effects caused by the cubane hydrogen atoms interacting with ethynyl groups. These interaction profiles can then be used as a guide for designing cubane bioisosteres of known materials and drugs containing phenyl moieties.
RESUMO
Herein, an improved methodology for aryl-cubane cross-coupling is reported. The peculiarities of the cubane core and its behavior during cross-coupling conditions were analyzed, while the versatility of this adapted Baran cross-coupling methodology was demonstrated by the synthesis of various aryl-cubane systems, including coupling products of cubanes and porphyrins. Furthermore, arm extension of alkynyl-cubanes by Sonogashira reactions is demonstrated, showcasing the first proof of the stability of the cubane core in the presence of palladium catalysts.