α-Secondary alkyl amines are structural motifs frequently encountered in a wide variety of natural products and pharmaceuticals. The N-benzyloxycarbonyl (Cbz) compound is a widely used precursor, acknowledged for its efficacy in implementing a masked amine strategy to access a privileged moiety. Although reductive amination is conducted as a crucial portion of the pharmaceutical industry, direct catalytic access to alkyl Cbz-amine is still rare due to the low reactivity of carbamate. Here, we show a superacid organocatalyst enabled direct access to bioactive Cbz-protected α-secondary alkyl amines using general ketones as the starting material. Through the highly selective and robust catalytic process, a wide substrate scope including drug precursor scaffolds in preparative scalability (up to >99% yield) with practical pharmaceutical syntheses is achieved. The obtained N-Cbz products are found to possess strong cytotoxicities in in vitro bioactivity evaluations, indicating their potential as promising candidates for new anticancer drug discovery.

α-仲烷基胺是各种天然产物和药物中经常遇到的结构基序。N-苄氧基羰基 (Cbz) 化合物是一种广泛使用的前体，因其在实施掩蔽胺策略以获得特权部分方面的功效而受到认可。尽管还原胺化是制药工业的重要组成部分，但由于氨基甲酸酯的反应活性较低，直接催化获得烷基Cbz-胺仍然很少。在这里，我们展示了一种超强酸有机催化剂，能够使用一般酮作为起始材料直接获得生物活性 Cbz 保护的 α-仲烷基胺。通过高度选择性和稳健的催化过程，实现了广泛的底物范围，包括具有制备可扩展性（高达> 99％产率）的药物前体支架和实用的药物合成。在体外生物活性评价中发现所获得的N -Cbz 产品具有很强的细胞毒性，表明它们有可能成为新抗癌药物发现的有希望的候选者。