Divergent Synthesis of β-Fluoroamides via Silver-Catalyzed Oxidative Deconstruction of Cyclopropanone Hemiaminals

An expedient approach for the synthesis of challenging & beta;-fluoroamidesfrom readily accessible cyclopropanone equivalents is reported. Followingthe addition of pyrazole used here as a transient leaving group, silver-catalyzedregiospecific ring-opening fluorination of the resulting hemiaminalleads to a & beta;-fluorinated N-acylpyrazole intermediatereactive to substitution with amines, ultimately affording & beta;-fluoroamides.The process could also be extended to the synthesis of & beta;-fluoroestersand & gamma;-fluoroalcohols via the addition of alcohols or hydridesas terminal nucleophiles, respectively.

Automated summary

An expedient approach for the synthesis of challenging β-fluoroamides from readily accessible cyclopropanone equivalents is reported. Following the addition of pyrazole used here as a transient leaving group, silver-catalyzed regiospecific ring-opening fluorination of the resulting hemiaminal leads to a β-fluorinated N-acylpyrazole intermediate reactive to substitution with amines, ultimately affording β-fluoroamides. The process could also be extended to the synthesis of β-fluoroesters and γ-fluoroalcohols via the addition of alcohols or hydrides as terminal nucleophiles, respectively.