Carbonyl-stabilized sulfoxonium ylides (i.e., keto sulfoxonium ylides) represent an important class of reactive intermediates. These molecules are typically prepared by reaction between an activated carboxylic acid derivative (e.g., acid chloride) and an excess of dimethylsulfoxonium methylide at elevated temperatures. In this study we sought to develop conditions for the synthesis of keto sulfoxonium ylides directly from carboxylic acids and under mild conditions. This study began when we unexpectedly formed a keto sulfoxonium ylide during an attempted Corey-Chaykovsky reaction on an unsaturated phenol ester. This led us to consider developing conditions to prepare keto sulfoxonium ylides directly from carboxylic acids via intermediates similar to phenol esters, which are themselves made by treating the acid with a number of popular peptide coupling agents. In this study, we screened a variety of peptide coupling agents to determine their ability to convert carboxylic acids into keto sulfoxonium ylides. Additionally, optimization studies were performed to provide mild reaction conditions that minimized the required amounts of dimethylsulfoxonium methylene and peptide coupling agent. The scope of carboxylic acid substrate was evaluated, which demonstrated that keto sulfoxonium ylide formation occurred instead of competitive Corey-Chaykovsky reactions. We also probed the viability using similar methodology to form keto sulfonium ylides from the less stable dimethylsulfonium methylide. This presentation will discuss i) the results from screening a variety of peptide coupling agents, ii) optimal reaction conditions for ylide formation, and iii) the scope of sulfur ylide products that can be prepared using this methodology.

Preparation of keto sulfoxonium ylides from carboxylic acids

253rd National Meeting (2017)

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