1,3-Hydro-di/monofluoromethylation of N,N'-Cyclic Azomethine Imines with HCF2SO2Na/H2CFSO2Na via Photocatalytic Radical Addition.

The radical 1,3-hydro-di/monofluoromethylation of N,N'-cyclic azomethine imines with HCF2SO2Na/H2CFSO2Na via photoredox catalysis is described. This reaction exhibits broad functional group compatibility, providing the desired products in good yields. However, CF3SO2Na failed to produce the trifluoromethyl product. DFT calculations revealed that the transition state activation energy for radical trifluoromethylation was significantly higher and the isotropic charge repulsion makes it difficult for the CF3 radical to transfer electrons.

1,6-Nucleophilic Di- and Trifluoromethylation of para-Quinone Methides with Me3SiCF2H/Me3SiCF3 Facilitated by CsF/18-Crown-6.

The direct 1,6-nucleophilic difluoromethylation, trifluoromethylation, and difluoroalkylation of para-quinone methides (p-QMs) with Me3SiRf (Rf = CF2H, CF3, CF2CF3, CF2COOEt, and CF2SPh) under mild conditions are described. Although Me3SiCF2H shows lower reactivity than Me3SiCF3, it can react with p-QMs promoted by CsF/18-Crown-6 to give structurally diverse difluoromethyl products in good yields. The products can then be further converted into fluoroalkylated para-quinone methides and α-fluoroalkylated diarylmethanes.

Direct 1,6-Difluoromethylation of 3-Methyl-4-nitro-5-styryl Isoxazoles by Photoredox-Promoted Radical Addition.

The photoredox-catalyzed 1,6-difluoromethylation of 3-methyl-4-nitro-5-styrylisoxazole with HCF2SO2Na has been developed. Structurally diverse difluoromethylated products were obtained in good yields, and their further transformations were also investigated. The di-, tri-, and monofluoromethylation of the substrates were compared, and the yield of the difluoromethylation was the highest. DFT calculations revealed that in the difluoromethylation reaction the CF2H radical was nucleophilic, and the transition state activation energy was the lowest.

Synthesis of 4-Hydroxycarbazole Derivatives by Benzannulation of 3-Nitroindoles with Alkylidene Azlactones.

A general synthesis of 4-hydroxylcarbazoles by domino vinylogous conjugate addition/cyclization/elimination/aromatization of easily prepared 3-nitroindoles with alkylidene azlactones under mild and transition-metal-free conditions has been developed. This method was also applicable to other nitrosubstituted benzofused heterocycles such as 3-nitrobenzothiophene, 2-nitrobenzothiophene, and 2-nitrobenzofuran. The valuable tetracyclic carbazole derivatives, such as 6H-oxazolo[4,5-c]carbazole and 3,6-dihydro-2H-oxazolo[4,5-c]carbazol-2-one, were readily prepared from the product, demonstrating synthetic utility of this method.

TMSCFX2 (X = Cl, Br) as halofluorocarbene sources for the synthesis of halofluorocyclopropanes.

TMSCFX2 (X = Cl, Br; TMS = trimethylsilyl) have been developed as halofluorocarbene (CFX, X = Cl, Br) precursors for [2+1] cyclopropanation with alkenes. Structurally diverse halofluorocyclopropanes were obtained in good to excellent yields. It was found that the reactivity order of the three halofluorocarbene reagents (TMSCF2Br, TMSCFCl2, and TMSCFBr2) in halofluorocyclopropanation with 1,1-diphenylethylene can be very different under different reaction conditions.

Fluoroalkylation of Various Nucleophiles with Fluoroalkyl Sulfones through a Single Electron Transfer Process.

The fluoroalkylation of various nucleophilic reagents with (phenylsulfonyl)difluoromethyl (PhSO2CF2)-substituted phenanthridines was achieved to give fluorinated phenanthridine derivatives, which enables the construction of both carbon-heteroatom and carbon-carbon bonds via the substitution of the phenylsulfonyl group. Mechanistic studies indicated that these reactions proceed through a unimolecular radical nucleophilic substitution (SRN1) mechanism. It is worthwhile noting that in the cases of O-nucleophiles ( t-BuO- and PhO-), the addition of t-BuOK/PhCHO could significantly promote the reactions, due to the in situ formation of a highly reactive electron donor species through the interaction of t-BuOK, PhCHO, and the solvent DMF, which can effectively initiate the single electron transfer process.

[4 + 2] Annulation of 3-Nitroindoles with Alkylidene Malononitriles: Entry to Substituted Carbazol-4-amine Derivatives.

A general and transition-metal-free method for the construction of the carbazol-4-amine motif via a vinylogous Michael addition/cyclization/isomerization/elimination reaction of 3-nitroindoles with alkylidene malononitriles has been developed. This novel methodology allows the facile synthesis of a series of di- and trisubstituted carbazol-4-amine derivatives in moderate to good yields. A gram-scale experiment was successfully performed, highlighting the practicability of this method. Moreover, this strategy is also applicable to 3-nitrobenzothiophene, affording the corresponding dibenzo[ b, d]thiophen-1-amine derivatives in moderate yields.

Radical (Phenylsulfonyl)difluoromethylation of Isocyanides with PhSO2CF2H under Transition-Metal-Free Conditions.

An atom-economical method for radical (phenylsulfonyl)difluoromethylation of isocyanides with PhSO2CF2H under transition-metal-free conditions has been developed. A PhSO2CF2 radical is generated through the oxidation of PhSO2CF2- after the deprotonation of PhSO2CF2H in one pot. The reaction exhibits excellent functional-group tolerance and the resulting products can be further modified with the removal of a PhSO2 group to give other CF2-containing compounds.

Bis(difluoromethyl)trimethylsilicate Anion: A Key Intermediate in Nucleophilic Difluoromethylation of Enolizable Ketones with Me3 SiCF2 H.

A pentacoordinate bis(difluoromethyl)silicate anion, [Me3 Si(CF2 H)2 ](-) , is observed for the first time by the activation of Me3 SiCF2 H with a nucleophilic alkali-metal salt and 18-crown-6. Further study on its reactivity by tuning the countercation effect led to the discovery and development of an efficient, catalytic nucleophilic difluoromethylation of enolizable ketones with Me3 SiCF2 H by using a combination of CsF and 18-crown-6 as the initiation system. Mechanistic investigations demonstrate that [(18-crown-6)Cs](+) [Me3 Si(CF2 H)2 ](-) is a key intermediate in this catalytic reaction.

Copper-Mediated Aromatic 1,1-Difluoroethylation with (1,1-Difluoroethyl)trimethylsilane (TMSCF2 CH3 ).

A new method for the formation of 1,1-difluoroethyl copper species ("CuCF2 CH3 ") with 1,1-difluoroethylsilane (TMSCF2 CH3 ) has been developed. The "CuCF2 CH3 " species can be applied to the efficient 1,1-difluoroethylation of diaryliodonium salts under mild conditions, affording (1,1-difluoroethyl)arenes in good to excellent yields. This convenient procedure tolerates a wide range of functional groups and thus serves as a practical synthetic tool for the introduction of CF2 CH3 group(s) into complex molecules.

Copper-mediated aerobic (phenylsulfonyl)difluoromethylation of arylboronic acids with difluoromethyl phenyl sulfone.

A new method for the generation of the "PhSO2CF2Cu" species from readily available difluoromethyl phenyl sulfone (PhSO2CF2H) has been developed. The "PhSO2CF2Cu" reagent can be applied in (phenylsulfonyl)difluoromethylation of arylboronic acids, which affords a convenient approach to introducing the PhSO2CF2 group into aromatics.

A pH-responsive fluorescent [5]pseudorotaxane formed by self-assembly of cationic water-soluble pillar[5]arenes and a tetraphenylethene derivative.

The formation of a pH-responsive fluorescent [5]pseudorotaxane by self-assembly of cationic water-soluble pillar[5]arenes and a tetraphenylethene derivative was reported.

Copper-catalyzed cascade syntheses of 2H-benzo[b][1,4]thiazin-3(4H)-ones and quinoxalin-2(1H)-ones through capturing S and N atom respectively from AcSH and TsNH(2).

A copper-catalyzed cascade method has been developed to synthesize the 2H-benzo[b][1,4]thiazin-3(4H)-ones from 2-halo-N-(2-halophenyl)-acetamides 1 and AcSH via the S(N)2/deacetylation/coupling process, and to synthesize the quinoxalin-2(1H)-ones from 1 and TsNH(2) via the S(N)2/coupling/desulfonation process. The target products were obtained with diversity at three positions on their scaffolds.

An efficient cascade synthesis of various 2H-1,4-benzoxazin-3-(4H)-ones from o-halophenols and 2-halo-amides catalyzed by CuI.

A novel and efficient one-pot cascade synthesis of 2H-1,4-benzoxazin-3-(4H)-ones has been developed through copper-catalyzed coupling of o-halophenols and 2-halo-amides. Various 2H-1,4-benzoxazin-3-(4H)-ones with diversity at three substituents on their scaffold have been synthesized conveniently in good to excellent yields.