Donor-Acceptor Cyclobutanes and Their Application for Heterocycle Synthesis and Progress Towards Biselide A
type: CreativeWork
description: 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.
abstract: 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.
author: Machin, Benjamin
language: en_ca
keywords: dipolar cycloaddition, donor-acceptor cyclobutanes, alkyne, aldehyde, tetrahydrofuran, biselide A
date published: 2013-07-23
date modified: 2026-07-27T21:56:09Z
provider: Western University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: The University of Western Ontario

PropertyValue
property ID: Handle
value: https://hdl.handle.net/20.500.14721/36278