Catalytic Hydrotrifluoromethylation of Unactivated Alkenes

Mizuta, Satoshi; Verhoog, Stefan; Engle, Keary M.; Khotavivattana, Tanatorn; O’Duill, Miriam; Wheelhouse, Katherine M. P.; Rassias, Gerasimos A.; Médebielle, Maurice; Gouverneur, Véronique

doi:10.1021/ja401022x

Cited by 413 publications

(171 citation statements)

References 46 publications

(22 reference statements)

Supporting

Mentioning

162

Contrasting

Unclassified

Order By: Relevance

“…Although we cannot rule out the direct hydrogen abstraction of an alkyl/vinyl radical from ethanol (pathway (a) in Fig. 6) 34 , it is highly likely that the hydrotrifluoromethylated product is formed through alkyl or vinyl carbanion formation by the second SET from [Ca 2 N] þ Á e À to the radical and its protonation (pathway (b)) based on the results conducted in EtOD shown in Fig. 5.…”

Section: Substrate Scope For Hydrotrifluoromethylation Of Alkenesmentioning

confidence: 98%

“…The deuterated products (2a 0 , 4a 0 and 6a 0 ) were exclusively formed from the reactions, clearly confirming that the hydrogen of the -OH group on the ethanol is the actual source of hydrogen in this process. Namely, no hydrogen abstraction from a-C-H bond of ethanol occurred 34,35 .…”

Section: Substrate Scope For Hydrotrifluoromethylation Of Alkenesmentioning

confidence: 98%

“…In particular, the literature contains only a few reports of the hydrotrifluoromethylation of alkenes and alkynes [34][35][36][37] . Here, we report an environmentally benign, efficient and simple method for a radical-initiated hydrotrifluoromethylation reaction with alkenes and alkynes using the inorganic electride [Ca 2 N] þ Á e À as an electron donor.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Hydrotrifluoromethylation and iodotrifluoromethylation of alkenes and alkynes using an inorganic electride as a radical generator

et al. 2014

View full text Add to dashboard Cite

The trifluoromethyl (CF 3 ) group is a staple synthon that can alter the physical and chemical properties of organic molecules. Despite recent advances in trifluoromethylation methods, the development of a general synthetic methodology for efficient and selective trifluoromethylation remains an ongoing challenge motivated by a steadily increasing demand from the pharmaceutical, agrochemical and materials science industries. In this article, we describe a simple, efficient and environmentally benign strategy for the hydrotrifluoromethylation of unactivated alkenes and alkynes through a radical-mediated reaction using an inorganic electride, [Ca 2 N] þ Á e À , as the electron source. In the transformation, anionic electrons are transferred from [Ca 2 N] þ Á e À electrides to the trifluoromethylating reagent CF 3 I to initiate radical-mediated trifluoromethylation. The role of ethanol is pivotal in the transformation, acting as the solvent, an electron-releasing promoter and a hydrogen atom source. In addition, iodotrifluoromethylation of alkynes proceeds selectively upon the control of electride amount.

show abstract

Section: Substrate Scope For Hydrotrifluoromethylation Of Alkenesmentioning

confidence: 98%

Section: Substrate Scope For Hydrotrifluoromethylation Of Alkenesmentioning

confidence: 98%

See 1 more Smart Citation

Hydrotrifluoromethylation and iodotrifluoromethylation of alkenes and alkynes using an inorganic electride as a radical generator

et al. 2014

View full text Add to dashboard Cite

show abstract

“…The Gouverneur group used the Umemoto's reagent as a precursor of trifluoromethyl radicals in 2013 ( Figure 6) [30]. The hydrogenated radical trifluoromethylation of unactivated olefins in the presence of photocatalyst was reported for the first time by the ruthenium catalyst which catalyzed in the single electron reduction of electrophilic Umemoto reagent to generate CF 3 radicals.…”

Section: Reduction Of Trifluoromethyl Reagents To Produce Trifluoromementioning

confidence: 99%

Research progress on trifluoromethyl-based radical reaction process

Song

2017

IOP Conf. Ser.: Earth Environ. Sci.

View full text Add to dashboard Cite

Abstract. Due to the unique properties imparted by the trifluoromethyl group, such as high electron density and strong lipotropy, which effectively improve acidity, lipophilicity and metabolic stability of the molecule itself, trifluoromethyl-substituted organic compounds are becoming increasingly important as structural motifs in pharmaceuticals, agrochemicals and organic materials. In this review, we present several methods developed for the direct introduction of a trifluoromethyl group, beginning with its rich and storied history. Then the present article addresses mechanism and process in carbon-carbon bond forming reaction based on radical process which is divided into three parts according to the way of CF3 radical generation. Finally, challenges and opportunities of researches on trifluoromethylation reactions facing are prospected. IntroductionIt is well-known that organofluorine compounds are extremely rare in nature despite the relatively high abundance of fluorine in our earth's crust.The seeds of researches on fluorinated compounds were firstly planted in 1764, however, seeds didn't sprout until 1896 when Swarts successfully synthesized ethyl fluoroacetate [1]. And then the ingenious Balz-schiemann reaction moved the fluoro-organic chemistry field into a brand new stage with a better comprehension of the specific fluorine factors on the outcome of organic reactions [2].Psychotropic drugs containing F atom such as Fluphenazine was discovered in 1956 and 5-Fluorouracil in 1957 [3], brought greater hopes for cancer therapy as well as more attention on the application of fluorinated compounds. (Hetero)arenes bearing CF 3 groups constitute an indispensable part of numerous important drugs, including celecoxib, fluoxetine and fluazinam. Currently, the interest in fluoro-organic chemistry is at an all-time high.It is therefore apparent that the development of new methods for trifluoromethylation, especially in an efficient, mild and green way, is essential and necessary.It is noteworthy that new discoveries and developments of trifluoromethylation reactions are built on the researches on Trifluoromethyl reagents. Mechanisms corresponding to their regents' properties which are electrophilic, nucleophilic, or radical, can be divided into electrophilic trifluoromethylation; nucleophilic and radical. In this review, we 1) Categorize types of trifluoromethylation with presentation of the reagents in each section. 2) Introduce some recent examples of C-C bond formation based on radical way, which have appeared in the primary literature. Important earlier work in this field is also covered. 3) Focus our attention on summarizing the mechanism and propose the problems hindering the evolving chemical landscape that has engaged trifluoromethylation reactions.

show abstract

“…In 2013, Wu et al 90 and Mizuta et al 91 described two methods for hydrotrifluoromethylation of unactivated alkenes (Figure 43). In Qing's work, the nucleophilic CF 3 anion generated in situ from TMSCF 3 and NaOAc was oxidized by PhI(OAc) 2 to give CF 3 radical.…”

Section: Synthesis Of Alkenyl and Alkyl Trifluoridesmentioning

confidence: 99%