Institute of Organic Chemistry, University of Vienna, Vienna, Austria.
Nat Chem. 2022 Nov;14(11):1306-1310. doi: 10.1038/s41557-022-00991-4. Epub 2022 Oct 20.
The rapid assembly of complex scaffolds in a single step from simple precursors identifies as an ideal reaction in terms of efficiency and sustainability. Indeed, the direct single-step synthesis of complex alkaloid frameworks remains an unresolved problem at the heart of organic chemistry in spite of the tremendous progress of the discipline. Herein, we present a broad strategy in which dynamically assembled ternary complexes are converted into valuable azabicyclic scaffolds based on the concept of inverse hydride shuttle catalysis. The ternary complexes are readily constructed in situ from three simple precursors and enable a highly modular installation of various substitution patterns. Upon subjection to a unique dual-catalytic system, the transient intermediates undergo an unusual hydride shuttle process that is initiated by a hydride donation event. Furthermore, we show that, in combination with asymmetric organocatalysis, the product alkaloid frameworks are obtained in excellent optical purity.
从简单的前体中快速组装复杂支架是一种理想的反应，因为它在效率和可持续性方面具有优势。实际上，尽管该学科取得了巨大的进展，但直接从单一步骤合成复杂生物碱框架仍然是有机化学的核心问题。在此，我们提出了一种广泛的策略，其中动态组装的三元配合物基于逆氢化物穿梭催化的概念转化为有价值的氮杂双环支架。三元配合物可从三种简单的前体中就地制备，并可实现各种取代模式的高度模块化安装。在受到独特的双催化体系的作用后，瞬态中间体经历了一种不寻常的氢化物穿梭过程，该过程由氢化物供体事件引发。此外，我们还表明，结合不对称有机催化，可获得具有优异光学纯度的产物生物碱框架。
