Intramolecular [2 + 2] Cycloaddition Reactions of Allene-ynes: Exploring the Scope, Mechanism, and Application to the Synthesis of Carbocyclic SpirooxindolesOsbourn, Joshua M. (2012) Intramolecular [2 + 2] Cycloaddition Reactions of Allene-ynes: Exploring the Scope, Mechanism, and Application to the Synthesis of Carbocyclic Spirooxindoles. Doctoral Dissertation, University of Pittsburgh. (Unpublished)
AbstractThe thermal allene-yne [2 + 2] cycloaddition reaction provides quick and efficient access to alkylidene cyclobutene compounds containing a fused bicyclic ring structure. The mechanism of this reaction was examined computationally in collaboration with Dean Tantillo and Matthew Siebert and experimentally in our lab. Computational studies suggest that the allene-yne [2 + 2] cycloaddition reaction proceeds via a stepwise diradical pathway. It is commonplace for researchers to postulate diradical intermediates for thermally disallowed cycloaddition reactions, but rarely are experiments conducted to support their existence. Experimental efforts to trap the postulated diradical intermediate included appending a cyclopropane to various allene-yne substrates. In two examples, products resulting from cyclopropane ring opening were isolated and characterized, thus providing experimental evidence supporting a diradical intermediate. The scope of the thermal allene-yne [2 + 2] cycloaddition reaction was expanded to the preparation of spirocyclobutene oxindoles. Our investigation led to the discovery of a tandem thermal [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition reaction of propargyl esters to afford carbocyclic spirooxindoles. This methodology lent itself to the formation of both spirobicyclo[4.2.0]oxindoles and spirobicyclo[5.2.0]oxindoles in moderate yields. The scope of the reaction was expanded to the synthesis of potentially biologically active spirocyclobutene oxindole compounds. Transfer of chirality from an allene to the [2 + 2] cycloadduct was possible when using a tert-butyl substituted allene; however in the case of a propargyl acetate substrate, complete racemization was observed during the tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition reaction. We hypothesize that the bulkiness of the tert-butyl group and oxindole restricts rotation at the intermediate diradical and thus prevents racemization. The synthetic utility of the resulting [2 + 2] cycloadducts was briefly examined. The most notable transformations were conversion of the enolacetate of the spirooxindole to the corresponding ketone and α-acetoxyketone. Share
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