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A visible-light-induced nickel-catalyzed cross coupling of alkyl carboxylic acids with N-trifluoroethoxyphthalimide is described. Under purple light irradiation, an α-hydroxytrifluoroethyl radical generated from a photoactive electron donor–acceptor complex between Hantzsch ester and N-trifluoroethoxyphthalimide was subsequently engaged in a nickel-catalyzed coupling reaction with in situ-activated alkyl carboxylic acids. This convenient protocol does not require photocatalysts and metal reductants, providing a straightforward and efficient access to trifluoromethyl alkyl acyloins in good yields with broad substrate compatibility. The complex bioactive molecules were also compatible with this catalytic system to afford the corresponding products.

A cascade oxidative trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles with AgSCF3 is described. This protocol allows for the synthesis of novel bis(trifluoromethylthiolated) or trifluoromethylthiolated pyrrolo[1,2-a]indol-3-ones in moderate to good yields. Mechanistic investigations indicated that radical processes were probably involved in these transformations.

To date the carboacylation of alkenes has been reported only in single- and two-component methodologies. Here, the authors report a three-component nickel-catalyzed carboacylation of olefins which enables the rapid construction of ketones with high levels of complexity and diversity.

A Cu-mediated trifluoromethylation of benzyl, allyl and propargyl methanesulfonates with TMSCF3 was developed for the first time. This method offers a convenient and economical approach to various trifluoroethyl-containing compounds.

The straightforward synthesis of four gem-difluoromethylenated analogues 4–7 of boronolide is described. The key steps of the synthesis include the concise preparation of the key intermediates 12a–b through the indium-mediated gem-difluoropropargylation of aldehyde 9 with the fluorine-containing building block 11 and the efficient construction of α,β-unsaturated-δ-lactones 15a–b via BAIB/TEMPO-procedure.

We present a mechanistic investigation of Pd-catalyzed allylic substitution of cyclic gem-difluorinated carbonates 1 and 4, previously employed in the synthesis of 3',3'-difluoro-2'-hydroxymethyl-4',5'-unsaturated carbocyclic nucleosides in 17 steps. The substitution features a reversal of regioselectivity caused by fluorine.

This article described an unprecedented synthesis of trifluoromethylthiophosphonium salts from allyl trifluoromethyl sulfoxide and phosphines in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) through Mislow-Evans-type rearrangement. The resulting trifluoromethylthiophosphonium salts were firstly isolated and fully characterized. These fluoroalkylphosphonium salts, as exemplified by trifluoromethylthio triphenylphosphonium salt (6a), exhibited unique and versatile reaction with nucleophiles and deoxygenative trifluoromethylthiolation reaction of carboxylic acids. Furthermore, the photoredox catalytic tunable radical hydrotri-fluoromethylation and hydrotrifluoromethythiolation of unactivated alkenes with 6a was successfully developed. [ABSTRACT FROM AUTHOR]

A practical and efficient route for the stereoselective synthesis of (2R,3S)- and (2S,3R)-4,4,4-trifluoroisoleucines and (2R,3S)-4,4,4-trifluorovaline that was developed is described. The indium-mediated allylation of (R)-N-benzyl-2,3-O-isopropylideneglyceraldimine with 4-bromo-1,1,1-trifluoro-2-butene gave the desired homoallylic amine in high diastereoselectivity with moderate yield.

The syntheses of L- and D-beta-3E-deoxy-3E,3E-difluoronucleosides are addressed. Deoxo-Fluor is accidentally found to be efficient in reversing the hydroxyl configuration of a compound, and the desired product is provided in good yield.

A novel and efficient strategy was developed to synthesize [difluro(phenylseleno)methyl]-trimethysilane (PhSeCF2-TMS), which was further utilized as a nucleophilic difluoromethylating reagent to incorporate the [difluro(phenylselen)methyl]-trimethysilane into carbonyl compounds in good yield. The resulting PhSeCF2-containg alcohols could be conveniently converted into corresponding difluoromethyl alcohols by a radical deselenylation.

Research has been conducted on the L-2',3'-dideoxy-2'-trifluoromethyl-4'-thiocytidines. The synthesis of these compounds has been carried out from the alpha-trifluoromethyl-alpha,beta-unsaturated ester and the details are reported.

Results demonstrate a synthetic strategy for preparing the 3-trifluoroethylfurans, organofluorine compounds, starting from (Z)-2-alkynyl-3-trifluoromethyl allylic alcohols, by the palladium-catalyzed cyclization-isomerization reaction.

Research has been conducted on the preparation of ethyl 3-bromo-3, 3-difluoropropionate. Experiments include its treatment with active zinc dust in anhydrous DMF at room temperature.

The development of an efficient copper-mediated trifluoromethylation of terminal alkynes with nucleophilic trifluoromethylating reagent ([Me.sub.3]SiC[F.sub.3]) is reported. The developed method provides a general, straightforward, and practically useful method to prepare trifluoromethylated acetylenes.

An efficient and general strategy to gem-difluoromethylenated alpha,beta-unsaturated delta-lactones from various aldehydes under mild conditions in high yield was developed. This strategy combined with lipase-catalyzed enantioselectove acylation allowed stereoselective preparation of gem-difluoromethlylenated goniothalamin (S)-1 and (R)-1.

Two strategies were tried to synthesize 3'-deoxy-3'-difluoromethyl azanucleosides. After the first route failing, the key intermediate from trans-4-hydroxyproline in 8 steps was streoselectively prepared.

A new and efficient enantioselective synthesis of both enantiomers of syn-(3-trifluoromethyl)isoserine is achieved through a study. Ring opening of trifluoromethylated cyclic sulfates, derived from enantiopure trifluoromethylated vicinal diols, with various nucleophiles occurred exclusively at C2 with inversion of chirality.

The design and synthesis of gem-difluorinated sugar nucleosides are described. The key intermediate, 3-deoxy-3,3-difluoro-D-arabinofuranose 9, prepared from the chiral gem-difluorohomoallyl alcohol 12 is presented.

A short and efficient enantioselective synthesis of both enantiomers of anti-4,4,4-trifluorothreonine and 2-amino-4,4,4-trifluorobutanic acid was successfully developed. Trifluoromethylation of benzyl-protected bromoalkene provided key intermediate trifluoromethylated transdisubstituted alkene in good yield.

Research has been conducted on 4-trifluoromethyl- and 4-difluoromethyl-L-pyroglutamic acids. The authors describe the results of the synthesis of these compounds.

Research has been conducted on N-Boc- cis-4-trifluoromethyl-L- and N-Boc-cis-4-difluoromethyl-L-prolines. The results of diastereometrically pure synthesis of these compounds from N-Boc-4-oxo-L-prolone are described.

A novel and general route to alpha treatment of alpha-trifluoromethyl-alpha, beta-unsaturated ester and its use as a key intermediate in the synthesis of 2',3'-dideoxy-2'-trifluoromethylnucleosides is described.

An efficient asymmetric vinylogous Mannich (AVM) addition reaction of 3-alkenyl-2-oxindoles to α-fluoroalkyl aldimines has been developed. This reaction provided various optical active α-alkylidene- δ-amino-δ-fluoroalkyl oxindoles in excellent yields, complete γ-site regioselectivity, and excellent diastereoselectivities. [ABSTRACT FROM AUTHOR]

A general method to form a C(SP³)-SCF3 bond via copper-mediated oxidative trifluoromethylthiolation of unactivated alkenes with stable nucleophilic AgSCF3 was developed. This protocol provides a direct and efficient access to a series of trifluoromethylthiolated allylic compounds with broad functional group tolerance. [ABSTRACT FROM AUTHOR]

Copper-catalyzed aerobic oxidative trifluoromethylation of readily accessible H-phosphonates was demonstrated for the first time. This method not only provides an alternative method for the facile synthesis of a series of biologically important CF3-phosphonates, but also demonstrates the first example of the efficient construction of a P-CF3 bond via transition-metal catalysis. [ABSTRACT FROM AUTHOR]

This article describes the copper-catalyzed oxidative trifluoromethylation of heteroarenes and highly electron-deficient arenes with CF3SiMe3 through direct C-H activation. In the presence of catalyst Cu(OAc)v, ligand 1,10-phenanthroline and cobasestert-BuONa/NaOAc, oxidative trifluoromethylation of 1,3,4-oxadiazoles with CF3SiMe3 proceeded smoothly using either air or di-tert-butyl peroxide as an oxidant to give the corresponding trifluoromethylated 1,3,4-oxadiazoles in high yields. Di-tert-butyl peroxide was chosen as the suitable oxidant for oxidative trifluoromethylation of 1,3-azoles and perfluoroarenes. Cu(OH)2 and Ag2CO3 were the best catalyst and oxidant for direct oxidative trifluoromethyaltion of indoles. The optimum reaction conditions enable oxidative trifluoromethylation of a range of heteroarenes that bear numerous functional groups. The prepared trifluoromethylatedheteroarenes are of importance in the areas of pharmaceuticals and agrochemicals. The preliminary mechanistic studies of these oxidative trifluoromethylations are also reported. [ABSTRACT FROM AUTHOR]

A number of fluorinated versatile building blocks (synthons) were developed for the synthesis of trifluoromethylated and gem-difluoromethylenated biologically interesting compounds. Extensive studies have demonstrated that fluorine atoms have profound stereoelectronic effects on neighboring groups, leading to special performance of the fluorine-containing compounds in reactions. It was found that, in comparison with their nonfluorinated counterparts, a C-O bond adjacent to a CF2 group was more stabilized which made it hard to be substituted in a SN2 way; double bond next to fluorinated groups was too electron deficient to participate in ring-closing-metathesis (RCM) reactions, and the carbocation that was strongly destabilized by neighboring CF2 group reacted immediately with nucleophilic molecules to produce unexpected product and so on. Thus improved methodologies were developed to achieve the desired transformations. The conformational analysis of difluorothiouridine suggested that the gem-difluoro atoms governed the overall conformation of the sugar ring and nucleobase. The biological evaluation of the synthetic difluoromethylenated azasugars towards eight glycosidases showed that the CF2 group decreased the pKa of azasugars which enhanced their binding affinity and selectivity to glycosidases. [ABSTRACT FROM AUTHOR]