Urea‐Induced Acid Amplification: A New Approach for Metal‐Free Insertion Chemistry

Abstract

The enhanced catalytic activity of difluoroboronate ureas proved to be essential as an acidity amplifier to promote metal-free O-H and S-H insertion reactions of α-aryldiazoacetates in high yield. This methodology was found to be generally applicable to a broad substrate scope and presents a conceptually new approach for organocatalytic diazo insertion reactions. Mechanistic investigations suggest that the reaction pathway involves a urea-induced protonation of the α-aryldiazoester.

Divergent Roles of Urea and Phosphoric Acid Derived Catalysts in Reactions of Diazo Compounds

“…Despite the unclear mode of action of urea catalysis in the context of α-aryl-α-diazo ester activation, excellent yields of both O-H and S-H insertion products were frequently isolated when α-aryl-α-diazo esters were treated with appropriate insertion partners in the presence of just 2.5 mol% of boronate urea catalyst 1 (Scheme 4). 7 Importantly, no reaction was observed if the boronate urea catalyst was omitted while otherwise keeping the reaction conditions identical. In our initial study, a variety of carboxylic acids were found to operate as insertion partners with elec-tron-rich α-aryl-α-diazo esters 5 to afford 6 in high yields.…”

Scope and Mechanism of Iridium Porphyrin-Catalyzed S–H Insertion Reactions between Thiols and Diazo Esters

“…The biological and medicinal importance of thioethers , drives the search for convenient and efficient strategies of forming C–S bonds. Several methods are used to synthesize thioethers, including use of acid and base catalysts. − Other approaches involve the use of iron­(III) porphyrin catalysts in the addition of disulfides to olefins, , while alternative routes to thioethers include palladium-catalyzed coupling of organic halides with thiols. , Furthermore, thioethers have been produced from copper-catalyzed reactions between diaryl disulfides and β-dicarbonyl compounds . An atom-economic method of forming new C–S bonds is the insertion of the carbene fragment of diazo compounds into the S–H bond of thiols, releasing N 2 as the only byproduct .…”

Synergistic NaBH4 Reduction/Cyclization of 2‐Aroylcyclopropane‐1‐carboxylates: Synthesis of 3‐Oxabicyclo[3.1.0]hexane Derivatives

“…The great pharmaceutical potential of this scaffold prompted us to search for new and efficient methods that would provide diversified structures in a minimum number of steps. As a result of their biological importance, many methods for the construction of 3‐oxabicyclo[3.1.0]hexanes have been developed 3‐Oxabicyclo[3.1.0]hexanes can be synthesized by various strategies, such as the Ireland–Claisen rearrangement procedure,, intramolecular cyclization reactions of aryldiazoacetates, Ru‐catalysed annulations, Pd‐promoted [2+1] cycloaddition reactions between dihydrofuran derivatives and alkynes, or Au‐catalysed cyclopropanation reactions of substituted (allyloxy)sulfonium ylides . Another interesting synthetic pathway, reported by Pathak and co‐worker, is based on the formation of single diastereomers of substituted 3‐oxabicyclo[3.1.0]hexanes through the reaction of the corresponding vinyl selenone with nitromethane, malononitrile, and dimethyl malonate in the presence of t BuOK in THF at room temperature .…”