Reductive Radical Cyclizations for Heterocycle Synthesis

发展现代高效的杂环构筑块合成方法对天然产物和药物的合成以及工业应用具有重要意义。该项目将开发的钛(III)催化的自由基环化反应将使中心吲哚、吡咯、吲哚利定和喹啉类化合物的非传统、灵活和直接的合成以及多官能化的吡啶成为可能。此外，3-氨基吲哚和3-吡咯等结构片段将直接可用，并可原位衍生化。以前，由于它们的不稳定性和有限的合成途径，这些分子类很少用于有机合成。所提出的创新的环化方法的适用性将在高效的天然产物的全合成中得到验证，如板蓝素A、米托吗宁和米托吉宁拟吲哚。该项目的成功完成将进一步确立钛(III)催化作为一种合成杂环的通用方法。

The development of modern and efficient methods for the synthesis of heterocyclic building blocks is of fundamental importance for the synthesis of natural products and drugs as well as industrial applications. The titanium(III)-catalyzed radical cyclizations that will be developed in this project will enable unconventional, flexible, and straightforward syntheses of central indole, pyrrole, indolizidine, and quinolizidine building blocks, as well as multifunctionalized pyridines. In addition, structural fragments such as 3-aminoindoles and 3-pyrroles will become directly available and can be derivatized in situ. Previously, these molecule classes were rarely employed in organic synthesis due to their instability and limited synthetic access. The applicability of the presented innovative cyclization methods will be demonstrated on highly efficient total syntheses of natural products such as isatisin A, mitragynin and mitragynin pseudoindoxyl. The successful completion of this project will further establish the titanium(III)-catalysis as a versatile method for heterocycle synthesis.