Synthesis of α‐Trifluoromethylated Ketones from Vinyl Triflates in the Absence of External Trifluoromethyl Sources

Abstract

A novel method for the conversion of vinyl triflates into α-trifluoromethylated ketones in the absence of external trifluoromethyl sources is described. This process accomplishes an efficient migration of the trifluoromethyl group of the triflate to the α-position in the ketone through a radical process. The reaction proceeds by the addition of a trifluoromethyl radical to the vinyl triflate and subsequent fragmentation of the trifluoromethane sulfonyl radical. Based on this reaction, a one-pot two-step procedure for the trifluoromethylation of ketones was developed. The method presented herein also allows the transfer of perfluoroalkyl groups from vinyl perfluoroalkanesulfonates, which are readily accessible from alkynes and perfluoroalkanesulfonic acids.

Direct Photoassisted α‐Trifluoromethylation of Aromatic Ketones with Trifluoroacetic Anhydride (TFAA)

“…The pure product was obtained after the chromatographic purification as colorless oil. Yield: 64%; 66 mg. R f = 0.22 (5% EtOAc in pet ether); 1 H NMR (301 MHz, CDCl 3 ) d 8.00-7.92 (m, 1H), 7.21-7.13 (m, 1H), 3.76 (q, J = 9.9 Hz, 1H); 13 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57…”

“…Recently, Kamimura et al . have shown another interesting protocol for the synthesis of α‐CF 3 ketones . Vinyl triflates derived from a ketone can be rearranged to α‐CF 3 carbonyl compounds in the presence of a radical initiator, e. g .…”

“…[12] Recently, Kamimura et al have shown another interesting protocol for the synthesis of a-CF 3 ketones. [13] Vinyl triflates derived from a ketone can be rearranged to a-CF 3 carbonyl compounds in the presence of a radical initiator, e. g. triethyl borane (BEt 3 ). The same rearrangement can also be performed by photocatalysis as shown by Liu et al [14] Despite these advancements, most of the reported procedures use CF 3 -sources which are expensive and all these procedures are based on a two-step approach for the trifluoromethylation of ketones.…”

α‐Functionalisation of Ketones Through Metal‐Free Electrophilic Activation

“…The highly reactive analogous intermediate C might reside in equilibrium with the vinyl triflate A' (Scheme 1 c). Although the formation of vinyl triflates from the corresponding acetophenones is well-established, [15] and they can be often purified by chromatography and isolated, the reactivity of such species with electron-donating groups at the para-position is scarcely reported due to their decreased stability. [16] Herein, we report, to the best of our knowledge, the first example of electrophilic ketone activation and subsequent metal-free a-arylation and oxyamination.…”

Visible-light-induced oxidant and metal-free dehydrogenative cascade trifluoromethylation and oxidation of 1,6-enynes with water

“…The trifluoromethylation and oxygenation of alkene and alkyne substrates have been achieved using various trifluoromethylating reagents and peroxides, persulfates, hypervalent iodine salts and oxygen as the oxidant and/or transition metal catalytic system ( Scheme 1 , eqn (1)). 8 – 14 Although different valuable approaches appear to have been incorporated into the –CF 3 group, still there is demand for mild and sustainable synthetic methods that avoid oxidants and heavy metals and are applicable to sensitive substrates for the construction of functionalized advanced heterocycles.…”