Enantio- and Regioselective CH-Functionalization of Cycloalkanes

在过去的十年中，金属催化的CH活化和随后的取代已经成为形成新的CC键的一种有效方法，消除了对起始原料的预官能化的需要，并使高级中间体或天然产物的快速多样化成为可能。传统上，合成化学依赖于官能团的相互转化。另一方面，CH-活化为靶向分子提供了合成路线，以前是不可能的，通常是对传统技术的补充。它有可能大大缩短合成序列，从而最大限度地减少化学废物，降低精细化学品的价格，并能够更有效地开发甚至生产具有药用活性的化合物。目前，CH-活化法正在从20世纪70年代的学术好奇走向成熟，成为合成化学工具箱中的一种标准方法。然而，由于有机分子中存在大量的CH键，特别是C(sp³)H键的活化仍然存在选择性差的问题：到目前为止，C(sp³)H键的区域选择性定向官能化还没有实现。在这个项目中，我将在以前的实验结果的基础上，开发一种模型系统的CH激活方法，在CH激活中具有前所未有的高水平控制。经过必要的第一步，该方法将被应用于从具有有趣药理活性的天然产物中快速合成小物质文库，从而展示其在全合成、药物化学和制药工业中的潜力。

During the last decade metal-catalyzed CH-activation with subsequent substitution has emerged as a powerful method to forge new CC-bonds, obviating the need for prefunctionalization of starting materials and enabling rapid diversification of advanced intermediates or natural products. Traditionally, synthetic chemistry relies on functional group interconversions. CH-activation on the other hand offers synthetic routes to target molecules previously impossible and often complementary to the traditional techniques. It holds the potential to dramatically shorten synthetic sequences, thus minimizing chemical waste, reducing prices of fine chemicals and enabling a more efficient development and even production of pharmaceutically active compounds. At the moment, CH-activation is maturing from the academic curiosity it was in the 1970s into a stan-dard method in the toolbox of synthetic chemistry. However, particularly C(sp³)H-activation still suffers from poor selectivity due to the vast number of CH bonds present in organic molecules: To this date, a regioselective, directed functionalization of C(sp³)H-bonds has not been realized. In this project, I will develop a method for CH-activation of a model-system with unprecedented high level of control in CH-activation, building on previous experimental results. After the necessary first steps, the method will be applied to rapidly synthesize a small substance library from a natural product with interesting pharmacological activities, thus demonstrating its potential in total synthesis, medicinal chemistry and pharmaceutical industry.