Kalb Annah E, Liu Mingxin, Bosso Megan I, Uyeda Christopher
Department of Chemistry, Purdue University West Lafayette Indiana 47907 USA
Chem Sci. 2022 Sep 8;13(37):11190-11196. doi: 10.1039/d2sc02696a. eCollection 2022 Sep 28.
A dinickel catalyst promotes the [2 + 2 + 1]-cycloaddition of two aldehyde equivalents and a vinylidene. The resulting methylenedioxolane products can be deprotected in one pot under acidic conditions to reveal α-hydroxy ketones. This method provides convenient access to unsymmetrical alkyl-substituted α-hydroxy ketones, which are challenging to synthesize selectively using cross-benzoin reactions. Mechanistic studies are consistent with an initial migratory insertion of the aldehyde into a dinickel bridging vinylidene. Insertion of the second aldehyde followed by C-O reductive elimination furnishes the cycloadduct. Under dilute conditions, an enone side product is generated due to a competing β-hydride elimination from the proposed metallacyclic intermediate. A DFT model consistent with the concentration-dependent formation of the methylenedioxolane and enone is presented.
二镍催化剂促进两分子当量的醛与一个亚乙烯基的[2 + 2 + 1]环加成反应。所得的亚甲基二氧戊环产物可在酸性条件下一步脱保护，以得到α-羟基酮。该方法为选择性合成不对称烷基取代的α-羟基酮提供了便利途径，而使用交叉安息香反应选择性合成这些化合物具有挑战性。机理研究表明，醛首先会迁移插入到二镍桥连的亚乙烯基中。第二个醛插入后，接着进行C-O还原消除，得到环加成产物。在稀溶液条件下，由于从假定的金属环中间体发生竞争性的β-氢消除反应，会生成一种烯酮副产物。本文提出了一个与亚甲基二氧戊环和烯酮的浓度依赖性形成相一致的密度泛函理论（DFT）模型。
