Copper catalysis trifluoromethylation

Carbazoles 292 and azaindoles were trifluoromethylated selectively to 294 under copper catalysis with the Ruppert—Prakash reagent in the presence of trimethyl borate, 1,10-phenanthroline, and KF as a base. This reaction is also applicable to a variety of other arenes and heteroarenes (140L4268). 

A similar approach has been chosen for the trifluoromethylation of alkynes (Scheme 8). Under copper catalysis, the trifluoromethyl acetylenes are formed from either the free terminal alkyne or from the corresponding alkynyl trifluoroborate [31, 32],... 

Both E- and Z-configured a-trifluoromethyl enones are accessible via a Meyer-Schuster-type rearrangement of propargylic alcohols (Scheme 13a) [43, 44]. Under copper catalysis, the is-configured enone is obtained. When adding a rhenium salt as co-catalyst, the Z-configured product forms preponderantly. A similar report shows... 

Another report concerning the trifluoromethylation of alkenes under copper catalysis based on gas-phase DFT calculations comes to a different conclusion [50]. This study points to a radical mechanism, with the copper(I) catalyst reducing reagent 1 by means of a single electron transfer (SET) as the key step in the catalytic cycle. 

Ye Y, Sanford MS (2012) Merging visible-light photocatalysis and transition-metal catalysis in the copper-catalyzed trifluoromethylation of boronic acids with CF3I. J Am Chem Soc 134 9034-9037... 

As with the synthesis of indoles, tandem catalytic processes have also received considerable attention. To this end, imidoyl chlorides have proved useful starting materials (Scheme 24.10, disconnection D-3) [71,72]. Scheme 24.14 presents an example from the Zhang group, where imidoyl chloride 31 can be combined with benzyl amine using copper catalysis to deliver the expected benzimidazole in excellent yield [71]. However, it was necessary to include an electron-withdrawing substituent on the imidoyl chloride substrate to ensure good reactivity for example, the trifluoromethyl substituent present in substrate 31. 

Qing reported a Cu-mediated trifluoromethylation of terminal allq nes using Ruppert s reagent as the CF3 source. Similar conditions were also used for the trifluoromethylation of heterocycles, such as oxadiazoles, benzimidazoles, benzoxazoles, benzothiazoles and indoles. Sodeoka reported trifluoromethylation of the indole C2 position using copper catalysis in conjunction with Togni s reagent. ... 

Gade reported the asymmetric trifluoromethylation of (3-ketoesters using copper catalysis in the presence of bisoxazoline ligands. Here, either Togni s or Umemoto s reagent was required as the CF3 electrophile source. Sodeoka " reported the copper catalysed trifluoromethylation of allylsilanes, as did... 

The related 6-trifluoromethyl-l,3-dioxin-4-ones underwent conjugate addition reactions with Gilman reagents, or with Grignards with copper(I) catalysis (Eq. 112). The 6-substituted compounds were also available, and were used to synthesise threonine and aZZo-threonine analogues [303]. Stark contrast between the behaviour of fluorinated and non-fluorinated compounds is revealed in Eq. (113). While benzylmagnesium chloride adds smoothly to the 6-methyl... 

Egami H, Ide T, Fujita M, Tojo T, Hamashima Y, Sodeoka M (2014) Dual catalysis with copper and rhenium for trifluoromethylation of propargylic alcohols efficient synthesis of a-trifluoromethylated enones. Chem Eur J 20 12061-12065. doi 10.1002/chem.201403447... 

Scheme 16 Synthesis of trifluoromethyl-1,3,4-oxadiazole 55 by copper acetate catalysis...

Imidazolidinone catalysis was also coupled with Lewis acid catalysis to effect trifluoromethylation of aldehydes (Scheme 15.108). In this instance the Lewis acid was required to activate the trifluoromethyl bearing Togni s reagent, a suitable electrophile for the reaction process. It was found that the best yields and enantiomeric excesses were obtained when copper(i) chloride was used. 

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