Donor-Acceptor Cyclobutanes and Their Application for Heterocycle Synthesis and Progress Towards Biselide A

The chemistry of cyclobutane-1,1-diester has been investigated with aldehydes and alkyne reaction partners independently of each other. Under Yb(OTf)3 catalysis donor-acceptor cyclobutanes undergo a formal [4+2] cycloaddition with aldehydes to generate tetrahydropyrans exclusively in a cis disposition. Activated aldehydes were generally well tolerated giving tetrahydropyrans in moderate to good yields (51 - 89%) whereas less reactive congeners gave lower yields (51 - 72%). All carbon reaction partners were used in BF3·OEt2 mediated conditions to afford an unexpected 2,3-dihydrooxepine product resulting from alkynyl addition and rearrangement. Aryl acetylenes were compatible with the reaction conditions and moderate yields were obtained (31 - 53%). When a silyl ether protected aryl acetylene was deployed the expected formal [4+2] cycloadduct is observed. The application of a water soluble Co(nmp)2 catalyst was used in the progress towards the polyketides natural product biselide A. Key reactions for the formation of a single diastereomer of an advanced stage intermediate included: Evans’ asymmetric aldol and a Prasad reduction to form a 1,3-syn diol exclusively which cyclized with Co(nmp)2 in high yield (93%). A tethering strategy will be used for the formation of the macrocyclic portion of the natural product.

Name thesis:degree_name

Ph D

Discipline thesis:degree_discipline

Chemistry

Grantor dc:publisher

The University of Western Ontario

Year dc:date.issued

2013

Author dc:creator

• Machin, Benjamin

Advisor dc:contributor.advisor

• Brian L. Pagenkopf

• dipolar cycloaddition
• donor-acceptor cyclobutanes
• alkyne
• aldehyde
• tetrahydrofuran
• biselide A

Language dc:language.iso

en_ca

Handle dc:identifier.uri

https://hdl.handle.net/20.500.14721/36278

OAI identifier oai:identifier

oai:uwo.scholaris.ca:20.500.14721/36278