Use of the Nascent Isocyclic Ring to Anchor Assembly of the Full Skeleton of Model Chlorophylls

The chlorophyll skeleton contains a chlorin macrocycle and an annulated fifth (or isocyclic) ring bearing 131-oxo and 132-carbomethoxy substituents. The isocyclic ring has traditionally been constructed by annulation of an intact tetrapyrrole macrocycle. Here, a complementary route employs reaction of a gem-dimethyl-substituted dihydrodipyrrin–carboxaldehyde (AD half) and a dipyrromethane bearing a 3-methoxy-1,3-dioxopropyl group (BC half). A McMurry-like reaction of a 2-(2-nitro-5-oxohexyl)­pyrrole was employed to construct the second pyrrole ring in one of three BC halves, whereas the other two were prepared by known routes. An AD half and a BC half were joined by Knoevenagel condensation at room temperature, affording the AD,BC-substituted 2-methoxycarbonyl-2-propenone. The subsequent reaction of three AD, BC-propenones (mixture of Z,E-isomers) in CH3CN containing InCl3 and In­(OTf)3 at 80 °C afforded the chlorophyll skeleton as the chloroindium­(III) chelate; the reaction proceeds via Nazarov cyclization (to form the isocyclic ring), SEAr (to construct the macrocycle), and 2e–,2H+ oxidation (to give the aromatic chromophore). The absorption spectra of the complexes closely resemble that of chlorophyll a. The present work exploits the nascent isocyclic ring as an anchor for directed assembly of the AD and BC halves, forming both the chlorin macrocycle and the isocyclic ring in a single-flask transformation.

叶绿素骨架包含一个chlorin大环（chlorin macrocycle）以及一个稠合的第五环（或称异环，isocyclic ring），该环带有131位氧代和132位甲氧羰基取代基。长期以来，异环均通过完整四吡咯大环（tetrapyrrole macrocycle）的稠合反应构建。本研究采用的互补合成路线，则通过偕二甲基取代的二氢二吡咯甲醛（dihydrodipyrrin–carboxaldehyde，AD片段）与带有3-甲氧基-1,3-二氧代丙基的二吡咯甲烷（dipyrromethane，BC片段）的反应来实现。我们使用类McMurry偶联反应，以2-(2-硝基-5-氧代己基)吡咯为原料，在3个BC片段中的1个上构建第二个吡咯环；其余2个BC片段则通过已报道的方法制备。在室温下通过Knoevenagel缩合（Knoevenagel condensation）将AD片段与BC片段偶联，得到带有AD、BC取代基的2-甲氧羰基-2-丙烯酮。将3种AD、BC取代的丙烯酮（Z、E异构体混合物）置于含有氯化铟(III)和三氟甲磺酸铟(III)的乙腈溶液中，于80 ℃下反应，得到以氯铟(III)螯合物形式存在的叶绿素骨架；该反应依次经历纳扎罗夫环化（Nazarov cyclization，形成异环）、亲电芳香取代（SEAr，构建大环）以及2e⁻、2H⁺氧化（生成芳香生色团）三个步骤。该螯合物的吸收光谱与叶绿素a的吸收光谱高度相似。本研究利用新生的异环作为锚点，实现AD与BC片段的定向组装，在一锅法反应中同时构建chlorin大环与异环。