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Brønsted酸催化的瞬态烷基烷- 2h -吡咯和烷基烷- 3h -吡咯的环加成，用于对映选择性合成复杂的、吡咯融合的氮杂环。结构上相关的，但明显更稳定的烷基烷- 3h -吲哚在杂环合成中被广泛使用，而相应的烷基烷吡咯几乎是未知的。我们相信它们具有巨大的合成潜力，特别是通过环加成来立体选择性合成多种杂环化合物，我们希望在这个项目中从最广泛的意义上加以利用。具体来说，我们打算研究[6p+2p]-和[6p+4p]-环加成烷基烷- 2h -吡咯和烷基烷- 3h -吡咯与各种富电子的烯烃、二烯和1,3偶极子，以便一步合成具有高对映选择性的双环、吡咯融合杂环，这在以前是无法实现的。相应的吡咯-2-和吡咯-3-苯酚将被用作环加成的底物，在binol -磷酸催化下，它们将分别脱水成Brønsted酸结合的、瞬态的和高活性的烷基烯-2-和烷基烯-3-吡咯。然后它们又会在原位与富含电子的2p-和4p组分发生反应。预计的综合是基于扎实和成功的初步工作。此外，我们打算通过理论计算来研究环加成的机理。

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.