The isolation of many biologically active cyclooctanoid natural products in recent years has led to greater interest towards synthetic techniques capable of establishing 8-membered rings. Traditional annulation techniques used to make 5- and 6-membered rings are often ineffective due to higher entropic and enthalpic barriers to creating 8-membered rings. The Ovaska group has developed a microwave assisted technique utilizing a 6-exo dig cyclization of properly substituted 5-alkyn-1-ols followed by an immediate [3,3] sigmatropic Claisen rearrangement. However, in order for the reaction to go forward at a reasonable rate the sluggishness of the 6-exo dig cyclization must be counteracted, either by activating the triple bond with an electron-withdrawing group or pushing the reactive sites closer together by installing alkyl groups along the chain of the reactant. It is hypothesized that use of groups other than alkyl substituents, which have limited synthetic utility, is also possible. This thesis discusses efforts towards expanding this method to include reactants with a nitrogen installed between the alcohol and alkyne of the substrate. The strategy depends on the lone pair of the nitrogen and also a bulky protecting group on the nitrogen functioning sterically similar to alkyl substituents.
Theopold, Nikolas, "Synthesis of Nitrogen Containing Cyclooctanoid Structures via Tandem 6-exo dig Cyclization/Claisen Rearrangement" (2018). Chemistry Honors Papers. 22.
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