Doctor of Philosophy
Brian L. Pagenkopf
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.
Machin, Benjamin, "Donor-Acceptor Cyclobutanes and Their Application for Heterocycle Synthesis and Progress Towards Biselide A" (2013). Electronic Thesis and Dissertation Repository. 1380.