Extension of the enantioselective, Cu-catalyzed Henry reaction to a broadly applicable synthetic tool

对映体选择性亨利反应(=硝醛反应)在许多文献中被誉为有价值的C，C-键形成反应，因为生成的伯硝醇可以很容易地转化为手性的，多官能团的合成基团。事实上，实现这一目标的前提条件很好，因为现在存在着高度对映选择性的铜催化剂(包括我们的催化剂)，转化硝基化合物的可能性也是多种多样的。然而，后一种反应还没有在手性Henry产物上进行，或者只在单独的例子上进行过(例外：还原成？氨基醇)。因此，巨大的潜力仍未得到开发。这正是我们的项目发挥作用的地方：它旨在从方法上扩大对映选择性Henry反应，并通过与硝基的不同后续反应相结合，将对映选择性Henry反应推进为强大的、广泛适用的合成工具。追求以下三个子目标：(1)将对映选择性Henry反应扩展到储存稳定的醇(‘氧化’Henry反应)：这简化了实验工作，同时，它是铜催化的氧化-不对称C串联反应的第一个例子，(2)Henry反应和[3+2]-环加成反应的结合：最初得到的异恶唑(Id)亚胺可以转化为具有多达四个连续的、部分自由调整的立体中心的多功能、高度功能化的合成构筑块。(3)亨利反应和脱氮反应的结合：这允许获得对映光学，具有相同内球的仲醇，否则很难制备。已经进行了初步研究，证明了所有子项目的基本可行性。在此基础上，计划制定可靠、可广泛使用的方案(方法学部分)，并通过几种选定的天然产品和药物的对映选择性合成(面向应用的部分)来证明其实用性和有效性。这些应用涵盖了更简单的例子，其综合允许与其他方法以及结构上更复杂的系统进行直接比较。

Enantioselective Henry reactions ( = nitroaldol reaction) are praised in many publications as valuable C,C-bond forming reactions since the resulting ß-nitro alcohols can be easily converted into chiral, multifunctional synthetic building blocks. And indeed, the preconditions for that are excellent, because nowadays highly enantioselective Cu-catalysts exist (including our catalyst) and the possibilities for transforming nitro compounds are manifold. However, the latter reactions have not yet been carried out on chiral Henry products or have only been done on singular examples (exception: reductions to ß-amino alcohols). The huge potential is therefore still unexploited. And this is exactly where our project comes into play:It aims to methodologically expand the enantioselective Henry reaction and, by combination with diverse follow-up reactions of the nitro group, to advance the enantioselective Henry reaction into a powerful, broadly applicable synthetic tool.The following three subgoals are pursued: (1) Extension of the enantioselective Henry reactions to storage-stable alcohols ('oxidative' Henry reactions): This simplifies the experimental efforts and, at the same time, it is the first example of a Cu-catalyzed tandem reaction of the type oxidation–asymmetric C,C-coupling.(2) Combination of the Henry reaction with [3+2]-cycloaddition: The primarily resulting isoxazol(id)ines can be converted into versatile, highly functionalized synthetic building blocks with up to four continuous, in part freely adjustable stereocenters. (3) Combination of the Henry reaction with denitration: This permits access to enantiopure, secondary alcohols with identical inner spheres, which are otherwise difficult to prepare.Preliminary studies have been carried out that prove the fundamental feasibility of all subprojects. On this basis, it is planned to develop robust, broadly useable protocols (methodological part) and to proof their practicability and efficacy through the enantioselective synthesis of several selected natural products and drugs (application-oriented part). These applications cover simpler examples, the syntheses of which permits a direct comparison with other approaches, as well as structurally more complex systems.