Iron(III) chloride-based mild synthesis of phenanthrene and its application to total synthesis of phenanthroindolizidine alkaloids

• Published in: Tetrahedron Vol. 64; no. 32; pp. 7504 - 7510
• Main Authors: Wang, Kai-Liang, Lü, Mao-Yun, Wang, Qing-Min, Huang, Run-Qiu
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 04.08.2008; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Iron (III) chloride; Oxidative coupling; Phenanthrene ring system; Physical Sciences; Science & Technology; Total synthesis; Phenanthrene ring system; Iron (III) chloride; Oxidative coupling; Total synthesis; AROMATIC 1,5-HYDROGEN TRANSFER; ORGANIC-SYNTHESIS; phenanthrene ring system; LEWIS-ACID; EFFICIENT SYNTHESIS; INDOLIZIDINE; TYLOPHORINE DERIVATIVES; oxidative coupling; SODIUM-BOROHYDRIDE; QUINOLIZIDINE; iron (III) chloride; CHEMICAL EXAMINATION; total synthesis; OXIDATIVE COUPLING REACTIONS
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2008.06.003

Iron(III) chloride has been used to prepare polymethoxy-substituted phenanthrene-9-carboxylic acid via intramolecular oxidative coupling at room temperature in excellent yields. Mild reaction conditions and the use of environmentally friendly FeCl 3 provide a novel practical route for the synthesis of the important phenanthrene ring. The further application of this protocol as the key step to total synthesis of tylophorine, deoxytylophorinine, and antofine was achieved starting from readily available pyrrole in 48%, 44%, and 46% overall yields, respectively. This new and efficient strategy enjoys a number of advantages. The experimental procedure is simple under mild conditions, atom economy is very high without any protecting-group, starting materials are cheap or easily prepared. Hence this short and practical method is applicable to large-scale production. [Display omitted]