Metal catalyzed generation of reactive benzomethane intermediates for the synthesis of benzopyrans, tetrahydroquinolines and chiral aryl methanes

Benzopyrans and tetrahydroquinolines are motifs commonly found in natural products and pharmaceuticals. Each of these privileged scaffolds have a common benzomethane moiety. Iron (III) salts generate benzomethane intermediates from o-hydroxybenzyl alcohols or o-aminobenzyl alcohols under mild reaction conditions. These in situ generated intermediates can be trapped by olefins in a [4+2] cycloaddition reaction. Furthermore, isolation of unsymmetrical di- and triaryl methanes from a reaction with o-hydroxybenzyl alcohols and methyl eugenol demonstrate Friedel-Crafts reactivity with the benzomethane intermediates. In this work, a one-pot, multicomponent reaction with phenols, aldehydes, and olefins provide efficient access to benzopyrans. Iron (III) salts mediate the initial benzomethane formation in a Friedel-Crafts alkylation between a phenol and aldehyde. The in situ generated benzomethane is trapped with an olefin to afford a benzopyran with rearomatization as the thermodynamic driving force of the reaction. The reaction is tolerant of electron-rich phenols, aromatic, aliphatic, and heterocyclic aldehydes and electron-rich olefins. The synthesis of Psiguajadial F demonstrates the utility of the two-component methodology of o-hydroxybenzyl alcohols and olefins. Psiguajadial F is a meroterpenoid natural product isolated from Psidium guajava. To date 26 meroterpenoid natural products have been isolated from Myrtaceae L. many of which have demonstrated potent biological activity against cancer cell lines. The synthetic challenges in Psiguajadial F include a bicyclo[4.3.1]decane, two quaternary carbons, five rings, three contiguous stereocenters about the pyran B-ring and a trans-cyclobutane. The core B-ring of the natural product is assembled in a convergent step using a o-hydroxybenzyl alcohol and an olefin. The penultimate benzyl deprotection and diformylation steps completed the synthesis. In collaboration, a cell viability assay determined the cytotoxicity of the synthetic material against liver cancer cells.

Author dc:creator

• Allen, Emily E.

Advisor dc:contributor.advisor

• Schaus, Scott E.

• Organic chemistry

Statement dc:rights

• Attribution-NonCommercial-NoDerivatives 4.0 International

Licence dc:rights.uri

• http://creativecommons.org/licenses/by-nc-nd/4.0/

Language dc:language.iso

en_US

Handle dc:identifier.uri

https://hdl.handle.net/2144/33086

OAI identifier oai:identifier

oai:open.bu.edu:2144/33086