One-Pot Construction of Polycyclic Indoles through Temperature-Dependent 1,3-Dipolar Cycloaddition and Cascade Rearrangement

Temperature-controlled protocol has been developed for the synthesis of polycyclic indoles using a 1,3-dipolar [3 + 2] cycloaddition reaction of biaryl-formyl-chalcones with N-substituted α-amino acids. Notably, under elevated temperatures and excess N-substituted α-amino acid, a 1,3-dipolar component, the reaction undergoes an unprecedented rearrangement, expanding its synthetic utility. Furthermore, the protocol enables access to novel polycyclic spiro-indoline frameworks and estrone-based drug-like derivatives, thereby highlighting its potential for late-stage functionalization and drug development applications. In addition, the synthetic efficacy of this versatile approach has been enhanced by implementing sequential one-pot processes by directly starting from 2-bromo-chalcones and exhibits broad substrate compatibility.