Meidlinger Daniel, Marx Lisa, Bordeianu Catalina, Choppin Sabine, Colobert Françoise, Speicher Andreas
Department of Organic Chemistry, Saarland University, Campus C4.2, 66123, Saarbrücken, Germany.
Laboratoire d'Innovation Moléculaire et Applications (LIMA), ECPM, UMR 7042, Université de Strasbourg/Université de Haute-Alsace, CNRS, 25 Rue Becquerel, 67000, Strasbourg, France.
Angew Chem Int Ed Engl. 2018 Jul 16;57(29):9160-9164. doi: 10.1002/anie.201803677. Epub 2018 Jun 15.
Macrocyclization is typically the key step in the syntheses of cyclophane-type natural products. Considering cyclophanes with axially chiral biaryl moieties, the control of atroposelectivity is essential with biological activity and is synthetically challenging. We report an atroposelective approach involving Heck cyclization, which for the first time enables the total synthesis of an enantiopure macrocyclic bis(bibenzyl), namely isoplagiochin D. An enantiopure sulfinyl auxiliary in the ortho position of a biaryl axis (still flexible) was used to induce an atropo-diastereoselective Heck coupling (up to 98 % de). The traceless character of the sulfinyl auxiliary enables the introduction of a hydroxy group to give the target molecule with 98 % ee as well.
大环化通常是环芳烷型天然产物合成中的关键步骤。对于具有轴手性联芳基部分的环芳烷来说，对映选择性的控制对于生物活性至关重要，并且在合成上具有挑战性。我们报道了一种涉及Heck环化的对映选择性方法，该方法首次实现了对映纯大环双（联苄）即异普拉吉奥钦D的全合成。在联芳基轴（仍具有柔性）的邻位使用对映纯亚磺酰基助剂来诱导非对映选择性Heck偶联（非对映体过量高达98%）。亚磺酰基助剂的无痕特性使得能够引入一个羟基，从而也得到了对映体过量为98%的目标分子。
