Synthesis of Trifluoromethyl-Substituted Allenols via Catalytic Trifluoromethylbenzoxylation of 1,3-Enynes

Abstract

Allenol has been identified as a versatile building block for organic synthesis, and numerous efforts have been made to synthesize and apply allenol. However, limited efforts have been made to obtain a trifluoromethyl-substituted allenol. Here, by using a readily available 1,3-enyne as the starting material, a coppercatalyzed trifluoromethylbenzoxylation process was developed for efficient synthesis of trifluoromethyl-substituted allenols using Togni-II reagent as the reaction partner. Triple roles of the Togni-II reagent, including as the source of the trifluoromethyl group, as the source of the hydroxyl group, and as the oxidant, were elucidated in this transformation. Moreover, late-stage diversification was performed, which revealed the application potential of trifluoromethyl-substituted allenols for the preparation of various trifluoromethyl-substituted compounds.

Synthetic and mechanistic study on the conjugate isothiocyanation of enones with trimethylsilyl isothiocyanate

“…This selectivity is dependent on the enone substrate, but the NCS isomer could be easily purified by column chromatography. This reactivity represents one of the few examples where TMSNCS is reported as a reagent for the formation of isothiocyanates (-NCS), [40][41][42][43][44] while there are many examples of its use to form thiocyanates (-SCN). [45][46][47] First, we checked the electronic effects of the aromatic substituents and found that enones with electron-donating (Me, OMe) and electron-withdrawing (CN, F, CF 3 , NO 2 ) groups at the para position of the phenyl ring were well-tolerated, giving the desired isothiocyanato products (2b-2g) in excellent yields (87-94%).…”

Emerging Trends in Copper-Promoted Radical-Involved C–O Bond Formations

“…Using Togni-II reagent, Yang and Cao developed an efficient method for the copper-catalyzed radical trifluoromethylbenzoxylation of 1,3-enyne derivatives ( 111 ) for preparing CF 3 -substituted allenols ( 112 ). (Scheme d) . Notably, mechanistic studies also provide some evidence suggesting that in this reaction, Togni-II reagent plays three roles: the oxidant, the CF 3 -radical source, and the oxygen-functionality sources.…”

“…(Scheme 7d). 82 Notably, mechanistic studies also provide some evidence suggesting that in this reaction, Togni-II reagent plays three roles: the oxidant, the CF 3 -radical source, and the oxygen-functionality sources. of 1,3-enynes with different substituted alkene moieties to produce valuable trifluoromethyl-substituted allenolates in good yield.…”

“…(Scheme 7d). 82 Notably, mechanistic studies also provide some evidence suggesting that in this reaction, Togni-II reagent plays three roles: the oxidant, the CF 3 -radical source, and the oxygen-functionality sources. Furthermore, the addition of a catalytic amount of B 2 pin 2 is beneficial for activating the Togni-II reagent toward the SET reduction.…”

Remote Radical 1,3-, 1,4-, 1,5-, 1,6- and 1,7-Difunctionalization Reactions

“…The Yang and Cao group, in 2023, reported a Cu-catalyzed ATRA reaction of 1,3-enynes with Togni II reagent for making trifluoromethylbenzoxylated allenes 24 ( Scheme 24 ) [ 56 ]. The Togni II reagent plays triple roles in the reaction process, including the source of CF 3 radical, the nucleophile for the second functionalization, and an oxidant for Cu catalysis.…”