Efficient synthesis of fluoroalkylated 1,4,2-oxathiazoles via regioselective [3 + 2]-cycloaddition of fluorinated nitrile oxides with thioketones

Abstract

Fluorinated acetonitrile oxides, generated from the corresponding hydroximoyl bromides in the presence of aryl, hetaryl, ferrocenyl, and cycloaliphatic thioketones, undergo efficient [3 + 2]-cycloadditions to give 3-fluoroalkylated 1,4,2-oxathiazoles in good to excellent yields. The reactions proceed regioselectively with no competitive formation of furoxans as dimers of the intermediate 1,3-dipoles.

Unraveling the Polarization Effect of Sulfur Atom on the Mechanism and Selectivity in the 32CA Involving C–S and C–O Interactions: A Rationalization Study Using Bonding Evolution Theory

“…Therefore, it is expected that the most appreciated interactions in this 32 CA reaction will take place between the most nucleophilic center of thioketone C, the S1 sulfur atom, and the most electrophilic center of nitrile oxide B, the C 3 carbon atom. In excellent agreement with the regioselectivty experimentally observed [18].…”

“…However, a pseudo-energetic balance character associated with the S1-O1 regioisomeric channel (D2 product) between reagent and product can be observed. Therefore, Relative Gibbs free and activation energies perceptibly imply that 32CA reaction between nitrile oxide B and thioketone B in the gas phase takes place via a strongly regioselective (regiospecific) fashion passing through TS3 yielding D1 as the unique kinetically and thermodynamically reachable cycloadduct, in excellent agreement with the experimentally observed results [18]. The summarized energetic graph is portrayed in Fig.…”

“…Scheme 3 32CA reactions of fluorinated nitrile oxide B toward thioketones C experimentally studied by Mlostoń and co-workers [18] As shown in Table 1, thioketone moiety presents a large electronic chemical potential to be 4.19 eV, slightly higher to that of nitrile oxide, 4.24 eV, suggesting that along this 32CA reaction thioketone is able to exchange electron density with a neighboring molecule, and therefore the global electronic density transfer (GEDT) will take place from the thioketone toward the nitrile oxide. The nucleophilicity value provides a considerable prominence to the thioketone moiety as a majority nucleophile (3.39 eV) to compare with that of nitrile oxide (1.73 eV), being classified as a strong nucleophile, however nitrile oxide was considered as a marginal nucleophile, it is worth mentioning that the presence of a great electron-withdrawing CHF2 group has mostly affected the nitrile oxide chemical parameters.…”

“…In our ongoing ambition, the present work will be dedicated to rationalize and characterize the reactivity, selectivity and molecular mechanism for the synthetic reaction for the preparation of generated in situ 1,4,2-oxathiazoles substituted C5-aryl via 32CA reaction between nitrile oxide and thioketone, experimentally taken into oversee by Mlostoń and co-worker [18] as displayed in Scheme 3, such reaction was carried out into two step, in one hand, the dehydrohalogenation of hydrogen bromide (Eq. 4, Scheme 3) and the subsequent interaction of C-S and C-O throughout nucleophilic/electrophilic electron density exchange via 32CA reaction (Eq.…”

Recent Developments on the Synthesis of Various Sulfur‐Containing Heterocycles via [3+2]‐ and [4+2]‐Cycloaddition Reactions with Thiocarbonyls

“…In 2017, Heimgartner reported a [3 + 2]-cycloaddition of fluorinated nitrile oxide and thioketones for the preparation of fluoroalkylated 1,4,2-oxathiazole derivatives (Scheme 4a). [14] The same group also disclosed the synthesis of 2,3-dihydro-1,3,4-thiadiazoles from heteroaryl thioketones, 23 and in situ generated diarylnitrile imines (22, Scheme 4b). Only formation of [3 + 2]-cycloadducts was observed in this case.…”