Show simple item record

dc.contributor.advisorBeeler, Aaron B.en_US
dc.contributor.authorFleming, Gabrielle Simoneen_US
dc.date.accessioned2020-02-26T16:50:58Z
dc.date.issued2019
dc.identifier.urihttps://hdl.handle.net/2144/39534
dc.description.abstractSeven-membered rings are a key structural motif in many bioactive natural product families but compared to five- and six-membered rings, there are substantially fewer methods for their synthesis. The Buchner ring expansion provides expedient access to seven-membered carbocycles in a single step from simple starting materials. Moreover, the products are highly oxidized, which is ideal for downstream functionalization and utilization in complex molecule synthesis and medicinal chemistry. Herein, we disclose our efforts and progress towards enabling the Buchner ring expansion as a safe and practical synthetic tool. The intermolecular Buchner ring expansion remains largely unused as a general method to access seven-membered rings due to poor selectivity and limited substrate scope that arise from the exothermic nature of the reaction. We have demonstrated that the regioselectivity of the intermolecular Buchner reaction is greatly improved under continuous flow conditions due to improved heat transfer and mixing. We disclose the first example of an asymmetric intermolecular Buchner reaction using disubstituted diazo esters in good to excellent enantioselectivity (up to 98% ee). The intramolecular Buchner reaction has been used in many total syntheses to access 5,7- and 6,7-bicyclic carbocyclic cores. However, toxic and explosive diazomethane has traditionally been used to synthesize the requisite a-diazocarbonyl precursors. To enable a safer synthesis, we have developed a method to synthesize a-diazocarbonyls from carboxylic acids via reaction of acid fluorides with trimethylsilyl diazomethane, which is known to be less hazardous than diazomethane. To fully leverage the potential of the novel highly oxidized seven membered rings obtained in the Buchner reaction we embarked on a search for selective reactions of the underexplored cycloheptatrienes. We performed reaction screens to provide a knowledge base and toolbox of reactions for manipulating the reactivity the cycloheptatrienes through oxidations, reductions, and cycloadditions. Finally, we disclose our efforts towards the development of a novel method for the synthesis of azepines from aryl diazoacetates and pyridine. Upon irradiation with blue light, aryl diazoacetates are photolyzed and undergo Buchner-type reactivity to afford azapines in moderate yields. Preliminary mechanistic studies and an investigation of the scope of the reaction are discussed.en_US
dc.language.isoen_US
dc.subjectOrganic chemistryen_US
dc.subjectBuchneren_US
dc.subjectChemistryen_US
dc.subjectFlowen_US
dc.titleEnabling the Buchner ring expansion as a practical synthetic toolen_US
dc.typeThesis/Dissertationen_US
dc.date.updated2020-02-10T23:03:26Z
dc.description.embargo2021-02-10T00:00:00Z
etd.degree.nameDoctor of Philosophyen_US
etd.degree.leveldoctoralen_US
etd.degree.disciplineChemistryen_US
etd.degree.grantorBoston Universityen_US


This item appears in the following Collection(s)

Show simple item record