Regio- and Stereoselective Allylic Trifluoromethylation and Fluorination using CuCF₃ and CuF Reagents

Abstract

Copper-mediated trifluoromethylation of allylic chlorides and trifluoroacetates was performed using a convenient Cu-CF3 reagent. The reaction is suitable for selective synthesis of allyl trifluoromethyl species. Mechanistic studies indicate that the reaction proceeds via a nucleophilic substitution mechanism involving allyl copper intermediates. The analogous Cu-F reagent was suitable for fluorination of allyl chlorides. Stereodefined cyclic substrates reacted regio- and stereoselectively.

Site selectivities in fluorination

“…According to their control experiments, the reaction may occur through an SN1 mechanism, but the details were not clear. In the case of copper fluoride-mediated allylic fluorinations of linear allylic chloride 16, the linear-product 17 was obtained (Scheme 13) [22] . This fluorination reaction is expected to be an SN2-like reaction (Finkelstein reaction) but other fluorides, such as CsF and LiF, were not reactive.…”

Advances in trifluoromethylation or trifluoromethylthiolation with copper $$\hbox {CF}_{3}$$ CF 3 or $$\hbox {SCF}_{3}$$ SCF 3 complexes

“…In 2012 and 2013, a copper-mediated trifluoromethylation of propargylic and allylic halides or trifluoroacetates employing (Ph 3 P) 3 CuCF 3 5 in THF or CDCl 3 as solvent was reported by Szabó and co-workers (Scheme 11). 32,33 The branched propargylic chlorides or trifluoroacetates 29 or 30 reacted with (Ph 3 P) 3 CuCF 3 5 in THF at room temperature or 50 • C to give 58-92% yields of the linear allenylic trifluoromethyl derivatives 31, in the majority of cases. 32 Under the optimized reaction condition, the substituted linear propargylic chlorides or bromides 27 gave the main products of trifluoromethylated alkynes 28 at room temperature.…”

“…32 In general, the cinnamyl chlorides 32 having an electrondonating group gave higher yields than that with an electron-withdrawing group. 33 Both linear and branched cinnamyl chlorides or trifluoroacetates 33 afforded the same terminal substituted olefins 34 in moderate to good yields (30-85%) (Scheme 11). 33 A plausible mechanism for the trifluoromethylation of allylic halides using (Ph 3 P) 3 CuCF 3 as CF 3 source was proposed by Szabó and co-workers, as shown in Scheme 12.…”

Decarboxylative Fluorination Strategies for Accessing Medicinally- Relevant Products

“…5). Therefore, this allylic substitution might proceed via a π–allyl intermediate, which has been invoked to explain substitution reactions of allylic halides and trifluoroacetates from well defined (PPh 3 ) 3 Cu–CF 3 complexes [17] and Cu–CF 3 complexes generated in situ [18]. …”