Reductive Radical Cyclizations for Heterocycle Synthesis

发展现代有效的杂环结构单元合成方法对于天然产物和药物的合成以及工业应用具有根本的重要性。钛（III）催化的自由基环化，将在这个项目中开发将使非常规的，灵活的，直接的合成中心吲哚，吡咯，indolizidine，和quinolizidine建筑块，以及多功能化的吡啶。此外，结构片段，如3-氨基吲哚和3-吡咯将成为直接可用的，可以在原位衍生。以前，这些分子类别很少用于有机合成，因为它们的不稳定性和有限的合成途径。所提出的创新的环化方法的适用性将被证明在高效的天然产物，如靛红A，mitragynin和mitragynin pseudoindoxyl的全合成。该项目的成功完成将进一步确立钛（III）催化作为杂环合成的通用方法。

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.