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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Developing a diastereoselective intramolecular [4+3] cycloaddition of nitrogen-stabilized oxyallyl cations derived
Andrew G Lohse1, Richard P Hsung, Mitchell D Leider
1Division of Pharmaceutical Sciences and Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53705, USA.
Abstract:
Efforts toward achieving a practical and diastereoselective intramolecular [4+3] cycloaddition of nitrogen-stabilized oxyallyl cations with tethered dienes are described. Epoxidation of N-sulfonyl substituted allenamides with dimethyldioxirane (DMDO) generates nitrogen-stabilized oxyallyl cations that readily undergo stereoselective [4+3] cycloaddition with dienes. Selectivity is found to depend on the tethering length as well as the stability of the oxyallyl cation intermediate, whether generated from N-carbamoyl- or N-sulfonyl-substituted allenamides. The use of chiral N-sulfonyl-substituted allenamides provided minimal diastereoselectivity in the cycloaddition, while high diastereoselectivity can be achieved with a stereocenter present on the tether. These studies provide further support for the synthetic utility of allenamides.
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