Universität Stuttgart, Institut für Organische Chemie, Pfaffenwaldring 55, 70569, Stuttgart, Germany.
Angew Chem Int Ed Engl. 2020 Jun 26;59(27):10944-10948. doi: 10.1002/anie.202001725. Epub 2020 Apr 30.
Chiral acyclic tertiary allylic alcohols are very important synthetic building blocks, but their enantioselective synthesis is often challenging. A major limitation in catalytic asymmetric 1,2-addition approaches to ketones is the enantioface differentiation by steric distinction of both ketone residues. Herein we report the development of a catalytic asymmetric Meisenheimer rearrangement to overcome this problem, as it proceeds in a stereospecific manner. This allows for high enantioselectivity also for the formation of products in which the residues at the generated tetrasubstituted stereocenter display a similar steric demand. Low catalyst loadings were found to be sufficient and the reaction conditions were mild enough to tolerate even highly reactive functional groups, such as an enolizable aldehyde, a primary tosylate, or an epoxide. Our investigations suggest an intramolecular rearrangement pathway.
手性非环状叔烯丙醇是非常重要的合成砌块，但它们的对映选择性合成通常具有挑战性。酮的催化不对称 1,2-加成方法的主要限制在于通过酮残基的空间区分来进行对映面分化。在此，我们报告了开发一种催化不对称的 Meisenheimer 重排来克服这个问题，因为它以立体定向的方式进行。这使得即使在生成的四取代立体中心的残基具有相似的空间需求的产物形成中，也可以实现高对映选择性。发现低催化剂负载量就足够了，并且反应条件足够温和，可以耐受甚至是高反应性的官能团，例如烯醇化醛、伯对甲苯磺酸酯或环氧化物。我们的研究表明存在分子内重排途径。
