Enantioselective, Brønsted acid-catalyzed cycloadditions of alkylidene-2H- and alkylidene-3H-pyrroles towards the rapid and stereoselective assembly of bicyclic nitrogen heterocycles

我们打算建立第一个布朗斯台德酸催化的短暂的亚烷基-2H-吡咯和亚烷基-3H-吡咯环加成反应，对映选择性合成复杂的，吡咯稠合的氮杂环。结构相关，但显着更稳定的亚烷基-3H-吲哚已发现广泛用于杂环合成，而相应的亚烷基吡咯几乎是未知的。我们相信，它们具有巨大的合成潜力，特别是通过环加成立体选择性合成多种杂环化合物，我们希望在最广泛的意义上利用这个项目。具体而言，我们打算研究[6p+2 p]-和[6p+4p]-亚烷基-2H-吡咯和亚烷基-3H-吡咯与各种富电子烯烃，二烯，和1，3-偶极环加成，以提供双环，吡咯稠合杂环在一个单一的步骤，具有高的对映选择性，这是以前没有访问。作为环加成反应的底物，将使用相应的吡咯-2-和吡咯-3-甲醇，在BINOL-磷酸催化下，预期其分别脱水为布朗斯台德酸结合的、瞬时的和高反应性的亚烷基-2-和亚烷基-3-吡咯。然后，它们又会与富电子的2 p和4p组分原位反应。预计的综合是基于坚实和成功的初步工作。此外，我们还打算通过理论计算来研究环加成反应的机理。

We intend to establish the first Brønsted acid-catalyzed cycloadditions of transient alkylidene-2H-pyrroles und alkylidene-3H-pyrroles towards the enantioselective synthesis of complex, pyrrole-fused nitrogen heterocycles. The structurally related, but significantly more stable alkylidene-3H-indoles have found widespread use in heterocyclic synthesis whereas the corresponding alkylidene pyrroles are virtually unknown. We are convinced that they bear an enormous synthetic potential for the stereoselective synthesis of a multitude of heterocyclic compounds in particular via cycloadditions, which we want to exploit in this project in the broadest sense. Specifically, we intend to study [6p+2p]- und [6p+4p]-cycloadditions of both alkylidene-2H-pyrroles and alkylidene-3H-pyrroles with various electronrich alkenes, dienes, and 1,3-dipoles in order to furnish bicyclic, pyrrole-fused heterocycles in a single step with high enantioselectivity which have not been accessible previously. As substrates for the cycloadditions the corresponding pyrrole-2- and pyrrole-3-carbinols will be employed which under BINOL-phosphoric acid catalysis are expected to be dehydrated to the Brønsted acid-bound, transient, and highly reactive alkylidene-2- and alkylidene-3-pyrroles, respectively. These in turn will then react in situ with the electronrich 2p- and 4p-components. The projected syntheses are based upon solid and successful preliminary work. In addition, we intend to study the mechanism of the cycloadditions through theoretical calculations.