Copper-Catalyzed Intermolecular Cyanotrifluoromethylation of Alkenes

Abstract

A novel and highly practical reaction for the copper-catalyzed intermolecular cyanotrifluoromethylation of alkenes is presented here. This methodology provides a general and straightforward way to synthesize a variety of useful CF3-containing nitriles, which can be used for further preparation of pharmaceutically and agrochemically important compounds in synthetic organic chemistry.

Photocatalyzed Cyanodifluoromethylation of Alkenes

“…An examination of the substituent effects in aryl alkenes showed that neither electron-withdrawing nor -donating groups had an obvious impact on the yields.A variety of functional groups were tolerated, such as ether, ester,k etone,c hloride,b romide,i odide,b oronic acid ester, and amide groups.The compatibility of this reaction with the reactive functional groups,i ncluding bromide (4-14, 4-15, 4-24), iodide (4-16), and boronic acid ester (4-12), allowed further CÀCc oupling transformations.T he HCF 2 /CN-containing estrone derivatives were synthesized by this cyanodifluoromethylation conversion, further demonstrating the synthetic utility of this method (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). An examination of the substituent effects in aryl alkenes showed that neither electron-withdrawing nor -donating groups had an obvious impact on the yields.A variety of functional groups were tolerated, such as ether, ester,k etone,c hloride,b romide,i odide,b oronic acid ester, and amide groups.The compatibility of this reaction with the reactive functional groups,i ncluding bromide (4-14, 4-15, 4-24), iodide (4-16), and boronic acid ester (4-12), allowed further CÀCc oupling transformations.T he HCF 2 /CN-containing estrone derivatives were synthesized by this cyanodifluoromethylation conversion, further demonstrating the synthetic utility of this method (4)(5)(6)(7)(8)…”

“…However,e fficient cyanodifluoromethylation of alkenes under mild conditions remains ac hallenging task. Inspired by the discovery of cyanotrifluoromethylation of alkenes, [13] we investigated the cyanodifluoromethylation of alkenes with Ph 3 P + CF 2 CO 2 À in the presence of an itrogen source and without external addition of any CN À source. Inspired by the discovery of cyanotrifluoromethylation of alkenes, [13] we investigated the cyanodifluoromethylation of alkenes with Ph 3 P + CF 2 CO 2 À in the presence of an itrogen source and without external addition of any CN À source.…”

“…[14] Therefore,w e screened the cyanodifluoromethylation of alkene 1a with the Ph 3 P + CF 2 CO 2 À /NaNH 2 system under photocatalytic conditions using Ir(ppy) 3 as the photocatalyst. Because ac opper source is usually required in cyanotrifluoromethylation of alkenes, [13] various Cu complexes were examined (entries 1-4) and CuI was found to be as uperior choice (entry 1). Increasing the loading of Ph 3 P + CF 2 CO 2 À led to an increase in the yield (entries 6-8).…”

Addition of CF3 across unsaturated moieties: a powerful functionalization tool

“…However, this reaction was also described with aliphatic and ortho , meta and para -substituted aromatic substrates with good yields using Cu(OTf) 2 as a catalyst, 8 as a trifluoromethylating agent and TMSCN as a cyanide source. 41 …”

Recent progress in the trifluoromethylation of alkenes with Togni's reagents

“…42 In most cases, alkenes 25 proceeded smoothly to transform into the cyanotrifluoromethylation products 26 in moderate to good yields, and the substrates bearing electron-donating groups gave higher yields than those containing electron-withdrawing groups on the aromatic rings. A possible mechanism for cyanotrifluoromethylation of alkenes with Togni's reagent 1 is shown in Scheme 14.…”