Synthesis of Aryl Ynol Ethers and Their Synthetic Applications

Ynol ethers are known as very important synthetic intermediates that are widely used in the syntheses of natural products and pharmaceuticals. The ynol ethers have also been used as ideal precursors of ketenes and surrogates of alkynes with a higher oxidation state in many reactions. However, few studies focused on the applications of aryl ynol ethers, because their synthetic methods are limited. To make aryl ynol ethers practical synthetic intermediates, we developed a direct and efficient method to synthesize aryl ynol ethers using coupling reactions between aryl iodides and alkoxyacetylides. The aryl ynol ethers participate in a [1,5]-hydride shift, which extrude alkenes to generate aryl ketenes. The aryl ketene intermediates were trapped with multiple nucleophiles to provide different aryl acetic acid derivatives and benzyl ketones. Additionally, we employed the aryl ketenes in a 6π electrocyclic ring closure reaction to yield hydroxynaphthalenes and quinolones. Moreover, we discovered a hetero-[2+2]-cycloaddition reaction between aryl ketenes and aryl ynol ethers, and the forming cyclobutenones could undergo a retro-4π/6π electrocyclization reaction to afford naphthlenes. Finally, we utilized this novel electrocyclization in the synthesis of dictyodendrins F, H, and I. In particularly, we used the hetero-[2+2]-cycloaddition reaction between aryl ynol ethers to form cyclobutenone rings followed by the rearrangement to produce a highly substituted carbazole. Subsequently, the N-acylation and the oxidative cyclization furnished the final skeletons of dictyodendrins. Our synthetic methodology of aryl ynol ethers largely broadens the application of ynol ethers and facilitates the syntheses of natural products and pharmaceuticals.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Organic Chemistry

Grantor

UT Southwestern Medical Center

Year dc:date.issued

2016

Author dc:creator

• Zhang, Wenhan

Advisor dc:contributor.advisor

• De Brabander, Jef K.

Committee members dc:contributor.committeemember

• Ready, Joseph M.
• Tambar, Uttam
• Chen, Chuo

• Ethers
• Ethylenes
• Iodides
• Ketones

Language dc:language.iso

en

Identifier

967597583

OAI record oai:identifier

https://utswmed-ir.tdl.org/server/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Autswmed-ir.tdl.org%3A2152.5%2F3957