Synthesis of Acyl Fluorides via DAST-Mediated Fluorinative C–C Bond Cleavage of Activated Ketones

Abstract

A new protocol for preparation of acyl fluorides was developed by recognizing activated ketones as starting materials. The method provides a different scope compared with previously reported methods that employ carboxylic acids as substrates. A working hypothesis of pull-and-push-driven fluorinative C–C bond cleavage was successfully demonstrated by the simple addition of diethylaminosulfur trifluoride (DAST) derivatives to α-oximinoketones. The designed reaction system led to a highly efficient and chemoselective reaction. The wide availability of the ketones allowed for a range of synthetically useful aryloyl and aliphatic acyl fluorides including those containing chiral skeletons. The method is mild, fast, scalable, and potentially one-pot operative.

Diversity-Oriented Synthesis Catalyzed by Diethylaminosulfur-Trifluoride—Preparation of New Antitumor Ecdysteroid Derivatives

“…The ability of DAST to promote the skeletal rearrangement of oximes to substituted amides (known as Beckmann-rearrangement) was previously reported [ 23 ]. Additionally, DAST was recently found to be a useful reagent to induce the Beckmann-fragmentation of α -oximinoketones resulting in the preparation of aryloyl and aliphatic acyl fluorides [ 24 ]. In accordance with the previous reports, the reaction of ecdysteroid 20-acetoximes with DAST could effectively furnish the corresponding amides and resulted in two different Beckmann products, whereas the single available hydroxyl group at the 14 α position was either eliminated ( 13 ) or substituted with fluorine ( 14 ).…”

Diversity-Oriented Synthesis Catalyzed by DAST – Preparation of New Antitumor Ecdysteroid Derivatives

“…The ability of DAST to promote the skeletal rearrangement of oximes to substituted amides (known as Beckmann-rearrangement) was previously reported [21]. Additionally, DAST was recently found to be a useful reagent to induce the Beckmann-fragmentation of α-oximinoketones resulting in the preparation of aryloyl and aliphatic acyl fluorides [22]. In accordance with the previous reports, the reaction of ecdysteroid 20-acetoximes with DAST could effectively furnish the corresponding amides and resulted in two different Beckmann products, whereas the single available hydroxyl group at the 14α position was either eliminated (13) or substituted with fluorine (14).…”

Diethylaminosulfur Trifluoride (DAST) Mediated Transformations Leading to Valuable Building Blocks and Bioactive Compounds

“…[45] The DAST mediated Beckmann fragmentation reaction was used in aryloyl and aliphatic acyl fluorides syntheses, which started from corresponding α-oximinoketones. [46] The reaction itself occurred under mild conditions and tolerated many Scheme 18. The final step of the total synthesis of plantazolicin A.…”

“…Scope of products. [46] selective fluorinative Beckmann fragmentation. The reaction proceeded under mild conditions with very good yields.…”