Novel methodology for the synthesis of the benz[a]anthracene skeleton of the angucyclines using a Suzuki-Miyaura/isomerization/ring closing metathesis strategy. Issue 1 (4th January 2018)

• Record Type: Journal Article
• Authors: Johnson, Myron M.; Ngwira, Kennedy J.; Rousseau, Amanda L.; Lemmerer, Andreas; de Koning, Charles B.
• Is Part Of: Tetrahedron. Volume 74:Issue 1(2018)
• Page Start: 12
• Page End: 18
• Publication Date: 2018-01-04
• Subjects: Metathesis -- Suzuki-Miyaura reaction -- Isomerization -- Angucyclines -- Benz[a]anthracenes; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2017.11.023
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: The synthesis of the benz[ a ]anthracene skeleton of the angucyclines is described. Key steps involve the Suzuki-Miyaura reaction, isomerization of an aromatic allyl substituent to the corresponding styrene, and the use of the ring closing metathesis reaction to construct a benzene ring. For example, exposure of 3-allyl-2-bromo-1, 4, 5-trimethoxynaphthalene to (2-formyl-4-methoxyphenyl)boronic acid under palladium catalysis conditions resulted in the formation of 2-(3-allyl-1, 4, 5-trimethoxynaphthalen-2-yl)-5-methoxybenzaldehyde. This 2-naphthyl benzaldehyde then underwent a Wittig reaction to furnish 3-allyl-1, 4, 5-trimethoxy-2-(4-methoxy-2-vinylphenyl)naphthalene. Isomerization of the allyl group of this compound afforded the diene, ( E )-1, 4, 5-trimethoxy-2-(4-methoxy-2-vinylphenyl)-3-(prop-1-en-1yl)naphthalene. Exposure of the formed diene to the Grubbs II catalyst resulted in the formation of the benzanthracene, 3, 7, 8, 12-tetramethoxytetraphene, which was easily oxidized to the corresponding quinone. Graphical abstract: