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Brnsted酸催化的瞬时亚烷基-2H-吡咯和亚烷基-3H-吡咯的环加成反应，以实现复杂的吡咯稠氮杂环的对映选择性合成。结构上相关但更稳定的亚烷基-~3H-吲哚已被广泛用于杂环合成，而相应的亚烷基吡咯几乎是未知的。我们相信，它们在立体选择性合成多种杂环化合物方面具有巨大的合成潜力，特别是通过环加成反应，我们希望在这个项目中从最广泛的意义上开发这一点。具体地说，我们打算研究亚烷基-2H-吡咯和亚烷基-~3H-吡咯与各种富含电子的烯烃、二烯和1，3-偶极的[6P~2P]-和[6P~4P]-环加成反应，以便一步合成具有高对映体选择性的双环、吡咯稠合杂环。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，它们在BINOL-磷酸催化下有望分别脱水为Brnsted酸结合的、瞬时的和高活性的亚烷基-2-和3-亚烷基吡咯。然后，它们又会与富含电子的2p和4p组分发生原位反应。预计的合成是基于扎实和成功的前期工作。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.