New Three-Step Domino Reaction, “Thiophilic Addition−β-Elimination of Fluoride−[3,3] Sigmatropic Rearrangement”:  Synthesis of α-Allylic and α,α-Bis(allylic) α-Trifluoromethyl Dithioesters

Abstract

The three-step domino reaction, "thiophilic addition of an organomagnesium reagent onto dithioester-beta-elimination of fluoride-[3,3] sigmatropic rearrangement", provides the product of formal regiospecific substitution of a fluorine atom by an allyl group. This mild and versatile methodology was applied to the synthesis of various alpha-allylic and alpha,alpha-bis(allylic) alpha-trifluoromethyl dithioesters.

Domino nucleophilic trifluoromethylations of alkyl perfluorodithioesters

“…We have previously reported such reactions between perfluorodithioesters and organolithium or organomagnesium reagents ( Fig. 1) [2,3]. Similar results were observed from difluorophosphonodithioacetates [4].…”

1‐(Trifluoromethyl)cyclopent‐3‐enecarboxylic Acid Derivatives: Platforms for Bifunctional Cyclic Trifluoromethyl Building Blocks

“…[5] This formal α-fluorine substitution is actually the result of two successive three-step domino transformations: thiophilic nucleophilic allylation, β-elimination of fluoride and σ [3,3] rearrangement. [5] Thus, benzyl α,α-diallyl dithioester 2 was prepared from benzyl pentafluorodithiopropanoate (1) and its RCM reaction was investigated, a task that may not be trivial due to the presence of sulfur. [6] Grubbs' I catalyst was indeed ineffective, but the cyclopentene derivative 3 was obtained in high yield by using 10 (2 ϫ 5) mol-% Grubbs' II catalyst (Scheme 1).…”

“…Although compound 3 may be converted quantitatively into the corresponding acid 4 following our reported procedure [7] (Scheme 1), we searched for a more straightforward approach to this cyclopentanecarboxylic acid derivative starting from the commercially available 3,3,3-trifluoropropanoic acid (5) and its methyl ester 6, more precisely via their enolates.…”

“…The diallylation could also be performed directly on the 3,3,3-trifluoropropionic acid (5). In this case, the reaction occurred by only using [Pd 2 (dba) 3 ]·CHCl 3 (2 mol-%) as the palladium source and gave the corresponding allyl α,α-diallyl ester 9, which was hydrolysed in situ to give the acid 8 in 71 % yield (Scheme 3).…”

“…Benzyl 2,2-diallyl-3,3,3-trifluorodithiopropanoate (2) was prepared as described previously. [5] 3,3,3-Trifluoropropionic acid (5) was produced by the Central Glass company. Benzyl 3,3,3-trifluoropropanoate (10) was prepared from 5 under classical conditions (BnOH in the presence of DCC and DMAP).…”