The continuous emergence of drug-resistant bacteria and the structural limitations of existing pharmaceuticals highlight the urgent need for novel molecular scaffolds. Compared to target-oriented synthesis (TOS), the goal of diversity-oriented synthesis (DOS) provides a powerful approach to generate structurally complex and diverse molecules, expanding the chemical space for drug discovery. This study aims to develop an innovative condition-driven DOS strategy to synthesize thiazolone-based spiro compounds featuring caged and fused scaffold. Using identical starting materials, the research investigates how variations in different conditions influence the formation of distinct skeletons. Key intermediates include COCF₃ and thiazolone precursors. Substituent effects were also examined to understand electronic and steric influences on product selectivity. The study reveals a strong correlation between electron-withdrawing substituents and improved caged product formation. These findings provide valuable insights into reaction condition–controlled molecular design, potentially guiding the efficient synthesis of novel bioactive compounds with unexplored pharmacological potential. Compared with conventional TOS or substituent-based DOS approaches, this study introduces a new paradigm by demonstrating that structural diversity can be achieved solely through manipulation of reaction parameters. This innovative, condition-driven synthetic strategy offers a competitive advantage in exploring new chemical spaces with minimal modification to starting materials, contributing to the advancement of modern organic synthesis and drug discovery methodologies.