A Unified Approach for the Synthesis of Conformationally Locked and sp ² ‐sp ³ Fused Hybrids

Aromatics are indispensable structural motifs in pharmaceuticals due to conformational rigidity, unique noncovalent interactions, and stability, but they can also bear negative consequences related to poor solubility and metabolism. On the other hand, sp 3 ‐hybridized structures address many of the deficiencies of aromatic counterparts. Based on this, we designed a systematic platform for the synthesis of hybrid sp 2 ‐sp 3 building blocks via benzyne cycloadditions, aiming to exploit a synergetic effect and explore new chemical space. The application of this strategy is demonstrated in the synthesis of Enalapril hybrid derivatives.