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Efficient Synthesis of Functionalized Aryl Spiro[2.2]pentanes and Vinylcyclopropanes Using Sulfones as Carbene Equivalents with Mechanistic Investigations

Year: 2025
Type: dissertation
Abstract: Spiro[2.2]pentanes have been studied for over a century, captivating synthetic and physical chemists due to their high strain and unique topology. Recently the aryl spiro[2.2]pentane scaffold has shown promise in small molecule drug leads and bioisosteres. However, synthetic strategies to access highly functionalized aryl spiropentanes are limited using state-of-the-art methods. Building on previous work in the group, we have developed a method for the synthesis of functionalized, aryl spiro[2.2]pentanes using dialkyl sulfone reagents, which behave as nucleophilic carbene equivalents. Using this strategy, we have synthesized 16 spiropentanes from 9 different arylmethylenecyclopropanes and 7 different sulfones in up to 81% yield. Attempts to synthesize spiropentanes using cyclopropyl sulfones instead afforded vinylcyclopropanes, via an elimination mechanism. We have 14 examples of vinylcyclopropanes derived from styrene starting materials synthesized in up to 65% yield. Understanding the mechanism by which these sulfones interreact with olefines to make strained rings may lead us to developing altered reaction conditions such as using more mild bases, stereoselective parameters, or working on a wider range of starting materials. We wish to explore the exact mechanism of the ring closure and elimination of the sulfinate to build cyclopropanes from styrenes via stereochemical probes. In doing so we can determine whether the mechanism proceeds via a back-side attack as in an SN2 reaction or from a front-side attack in accordance with computational data we have for a concerted SN1 pathway. We are in the process of building a chiral nonracemic starting product to subject to ring closure conditions and observe whether stereochemistry is retained (concerted SN1) or inverted (SN2). To date we are still working on building this starting material to test this hypothesis.
DOI: 10.17615/cp60-py30
Language: English
Field: Chemistry
Open Access status: green
OpenAlex ID: W7086895785
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