Rodríguez-Franco Carlos, Ros Abel, Merino Pedro, Fernández Rosario, Lassaletta José M, Hornillos Valentín
Instituto de Investigaciones Químicas (CSIC-US) and Centro de Innovación en Química Avanzada (ORFEO-CINQA), Avda. Américo Vespucio, 49, 41092 Sevilla, Spain.
Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), Universidad de Zaragoza, 50009 Zaragoza, Spain.
ACS Catal. 2023 Aug 30;13(18):12134-12141. doi: 10.1021/acscatal.3c03422. eCollection 2023 Sep 15.
A highly enantio- and diastereoselective dynamic kinetic resolution (DKR) of configurationally labile 3-aryl indole-2-carbaldehydes is described. The DKR proceeds via a Rh-catalyzed intermolecular asymmetric reductive aldol reaction with acrylate esters, with simultaneous generation of three stereogenic elements. The strategy relies on the labilization of the stereogenic axis that takes place thanks to a transient Lewis acid-base interaction (LABI) between the formyl group and a thioether moiety strategically located at the position. The atropisomeric indole products present a high degree of functionalization and can be further converted to a series of axially chiral derivatives, thereby expanding their potential application in drug discovery and asymmetric catalysis.
本文描述了对构型不稳定的3-芳基吲哚-2-甲醛进行的高度对映体和非对映体选择性动态动力学拆分（DKR）。该DKR通过铑催化的与丙烯酸酯的分子间不对称还原羟醛反应进行，同时生成三个立体ogenic元素。该策略依赖于由于甲酰基与位于特定位置的硫醚部分之间的瞬态路易斯酸碱相互作用（LABI）而发生的立体轴不稳定化。轴手性吲哚产物具有高度官能化，并且可以进一步转化为一系列轴向手性衍生物，从而扩大其在药物发现和不对称催化中的潜在应用。
