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Construction of carbo- and oxacycles using radical relay cyclizations initiated by alkoxy radicals

University of British Columbia

An investigation of a versatile radical relay cyclization methodology for the rapid construction of carbo- and heterocycles from simple linear precursors has been presented in this thesis. This thesis mainly focuses on 1,5-hydrogen atom translocation and subsequent cyclization reactions (radical relay cyclization reactions). In Chapter 1, an up-to-date literature review of this concept (radical relay cyclization) is presented including 1,5-hydrogen translocation reactions initiated by carbon radicals as well as oxygen and nitrogen radicals. In Chapter 2, the formation of cyclopentane and cyclohexane derivatives utilizing radical relay cyclization reactions initiated by alkoxy radicals has been described. The diastereoselectivity of final carbocycles is discussed. In Chapter 3, the formation of 1,2-disubstituted tetrahydrofuran and tetrahydropyran derivatives utilizing radical relay cyclization reactions has been described. With the incorporation of an oxygen atom into the precursors, the diastereoselectivity has been increased dramatically compared to carbon analogs. In Chapter 4, the formation of 2,3,5-trisubstituted tetrahydrofuran derivatives utilizing radical relay cyclization reactions has been described. With the strategic incorporation of an oxygen atom into cyclization precursors, 1,5-hydrogen atom translocation and subsequent cyclization reactions are able to compete over direct cyclization reactions and β-fragmentation reactions through the dative control. Furthermore, the incorporation of an oxygen atom into precursors enables 1,6-hydrogen atom translocation reactions to outcompete 1,5-hydrogen atom translocation reactions. In Chapter 5, the application of this radical relay cyclization methodology for the synthesis of the tetrahydrofuran fragment within (–)-amphidinolide K has been demonstrated. The final fragment in (–)-amphidinolide K can be achieved in 60% yield with a >95:5 ratio of cis to trans isomers.

Text

2013-08-07

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/44759

Chemistry

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/