The Liebeskind–Srogl Cross-Coupling Reaction as a Crucial Step in the Synthesis of New Squaramide-Based Antituberculosis Agents

The synthesis of
an extensive series of new squaramides with high
potential in treating drug-resistant tuberculosis employing the Liebeskind–Srogl
cross-coupling reaction is presented. Using the protocol given and
various substrates, we assessed the scope and limitations of our methodology
and prepared an extensive range of desired compounds. Moreover, 1H NMR spectra in solution show the presence of two rotational
conformers (rotamers) in special cases. The results of antimycobacterial
activity demonstrate the highly selective substrate specificity of
the tested squaramides, requiring an efficient and widely applicable
synthetic approach needed for the discovery of lead compounds. Our
synthetic strategy confirms the versatility of squaramides that can
be easily transformed into diverse functionalized molecules.