A Strategic Synthesis of Fluoroethers via Ring-Opening Fluorinative Beckmann Fragmentation

Abstract

An S N 1-type fluorination method for monofluoroethers is developed. The key to this reaction is fluorinative C−C bond cleavage that is driven by oxygen-assisted Beckmann fragmentation. To enable this transformation, cyclic α-aryloxyoximes derived from 3-coumaranone and 1-indanones were investigated as substrates, using N,N-diethylaminosulfur trifluoride (DAST) as a dual-role reagent of an oxime activator and fluoride donor. This method features the synthesis of an underdeveloped chemical motif with simple and mild operating conditions.

Editing Tetrasubstituted Carbon: Dual C–O Bond Functionalization of Tertiary Alcohols Enabled by Palladium-Based Dyotropic Rearrangement

“…We were particularly interested in the fluorination reaction, as this reaction converts tertiary alcohols to α-fluorinated tertiary alkyl ethers, which are structural units found in bioactive compounds. , For example, aryloxy-2-fluoroacetic acid derivatives 1 and 2 are synthetic auxins, and compound 2 is known to exhibit remarkable herbicidal activity with the added benefit of being more crop tolerant than the widely used aryloxyphenoxy­propanoic acid class of herbicides such as cyhalofop butyl ( 3 ) and clodinafop propargyl ( 4 ) (Scheme b) . While a variety of synthetic methodologies, including S N 2, − S N 1, − decarboxylative fluorination, − and gem -difunctionalization of α-diazoketone, , have been developed to access monofluoroalkyl ethers, the synthesis of α-fluorinated tertiary alkyl ethers has been reported only sporadically, , and no asymmetric synthesis has been reported to date. In this context, the direct conversion of easily available homochiral tertiary alcohols , to enantioenriched fluorinated tertiary alkyl ethers would be of particular interest (Scheme a).…”

Methyl Pyruvate Oxime as a Carbonyl Synthon: Synthesis of Ureas, Carbamates, Thiocarbamates, and Anilides

“…We noted that the direct amidation of 2 should be facile compared to that of normal esters due to enhanced electrophilicity by the α-oxime group . In addition, the oxime was considered as a leaving group in the second substitution stage, based on our prior studies regarding the Beckmann fragmentation . Although the Beckmann fragmentation has been underexplored compared to the Beckmann rearrangement, recently, its utility was demonstrated in the synthesis of complex molecules .…”