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

• Published in: Journal of organic chemistry 2020-01, Vol.85 (2), p.702-715
• Main Authors: Wang, Pengzhi, Lu, Futai, Lindsey, Jonathan S
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.9b02770

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.