Perfluoro alkyl 1,3-diketonates of cyclic and acyclic secondary amines

Cyclic and acyclic secondary amines were quaternized with perfluoroalkyl 1,3-diketones to form secondary ammonium perfluoroalkyl 1,3-diketonates in good yields. Saturated cyclic secondary amines, including morpholine, N-acetylmorpholine, 3-methyl-N-acetylpiperidine, 2,2,6,6-tetramethyl-4-aminopiperidine, 4,4-dimethylimidazoline, 1,3-bispiperidine propane, and acyclic secondary amines, di(n-propyl) amine, di(isopropyl) amine, di(n-butyl) amine, and di(isobutyl) amine were reacted with various fluorine-containing 1,3-diketones (1-5) to yield the corresponding 1,3-diketonates (6-29). The compounds were characterized by ¹H, ¹⁹F, and ¹³C NMR, electrospray MS, and elemental analyses. Melting points and T_g values were obtained by DSC. Thermal decomposition data (5% weight loss temperature) were recorded by TGA. X-ray single-crystal structures show that 9 and 26 crystallize in monoclinic space group P2(1)/c.     

Studies on sulfinatodehalogenation XXIV. Further study on sodium dithionite-initiated perfluoroalkylation of electron-rich aromatics

The application of the sulfinatodehalogenation reaction system for the perfluoroalkylation of electron-rich aromatics is further studied. It was shown that perfluoroalkyl iodides reacted with polyhydric phenols, N,N?dialkylanilines, 2,5-dimethylpyrrole, N?methylpyrrole initiated by Na₂S₂O₄?NaHCO₃ gave the corresponding perfluoroalkylated products in moderate to good yields.     

Palladium-catalyzed Heck reaction of in-situ generated benzylic iodides and styrenes

A palladium-catalyzed Heck reaction of in-situ generated benzylic iodides and styrenes has been achieved. The reaction proceeds in a one-pot manner through 1) addition perfluoroalkyl iodides to styrenes to give benzylic iodides, 2) followed by a palladium-catalyzed Heck coupling of the resulting benzylic iodides with the same alkenes in high regio- and stereoselectivity. A variety of perfluoroalkylated alkenes were obtained in moderate to excellent yields.     

Stable but Reactive Perfluoroalkylzinc Reagents: Application in Ligand‐Free Copper‐Catalyzed Perfluoroalkylation of Aryl Iodides

The aromatic perfluoroalkylation catalyzed by a copper(I) salt with bis(perfluoroalkyl)zinc reagents Zn(R_F)₂(DMPU)₂, which were prepared and then isolated as a stable white powder from perfluoroalkyl iodide and diethylzinc, was accomplished to provide the perfluoroalkylated products in good‐to‐excellent yields. The advantages of this reliable and practical catalytic reaction are 1) air‐stable and easy‐to‐handle bis(perfluoroalkyl)zinc reagents can be utilized, 2) the reagent is reactive and hence the operation without activators and ligands is simple, and 3) not only trifluoromethylation but also perfluoroalkylation can be attained.     

Direct perfluoroalkylation of non-activated aromatic C-H bonds of phenols

A simple procedure for the perfluoroalkylation of the aromatic ring of phenols under mildly basic conditions is described. Treatment of a variety of phenols with perfluoroalkyl iodide in the presence of the radical initiator V-70L and Cs₂CO₃ provided the corresponding perfluoroalkylated products in moderate to good yields. Generally, the reaction proceeded smoothly at room temperature to yield regioselectively perfluoroalkylated products.     

A mild and practical copper catalyzed amination of halothiophenes

We have found that N,N-dimethylethanolamine (deanol) is a useful solvent and ligand for copper catalyzed amination of a variety of unactivated and activated 2- or 3-halothiophenes. Primary amines, acyclic secondary amines, cyclic secondary amines and acyclic secondary amines with 2-hydroxyethyl functionality react with halothiophenes in moderate to excellent yields. The mildly basic conditions utilized are compatible with many functional groups. The amination of halobithiophenes has also been examined. The aminothiophenes produced by this method are important intermediates in a variety of electronic and optoelectronic materials.     

N1,N3-Diacyl-3,4-dihydropyrimidin-2(1H)-ones: neutral acyl group transfer reagents

Readily available N1,N3-diacyl-3,4-dihydropyrimidin-2(1H)-ones efficiently acylate ammonia, primary and secondary amines to furnish primary, secondary and tertiary amides in good to excellent yields. The wide applicability of the procedure is demonstrated by running the reactions in a neutral medium, easy isolation of products, recycling of the innocuous by-product and chemoselectivity of the transformation.     

Factors affecting the efficiency and stereoselectivity of α-amino acid synthesis by the Petasis reaction

The use of chiral secondary amines containing only one branched substituent has been shown to give optimal yields and stereoselectivities in the preparation of α-amino acids using the Petasis reaction. While the use of chiral primary amines generally gives products in low to moderate diastereoselectivity, chiral secondary amines generally give products in >95:5 diastereoselectivity. Additionally, the use of amines with two chiral (and by definition, branched) N-alkyl substituents results in significantly reduced yields with respect to to secondary amines with one or no branched N-alkyl substituents.     

High-yielding synthesis of 1-isoindolinone derivatives via palladium-catalysed cycloaminocarbonylation

1-Isoindolinone derivatives were synthesised in high yields (up to 89%) by using 2-iodobenzyl bromide and 2-iodobenzylamine as bifunctional substrates in palladium-catalysed carbonylation. Depending on the N-nucleophiles, two types of compounds were synthesised with 2-iodobenzyl bromide: the use of primary amines, including amino acid methylesters, resulted in the formation of N-substituted 1-isoindolinones, while secondary amines react both with the benzyl bromide and iodoarene moieties resulting in the corresponding ortho-(N-piperidino/morpholinomethyl)-benzamides. The parent 1-isoindolinone was obtained in a facile, highly chemoselective intramolecular aminocarbonylation of 2-iodobenzylamine. The mechanistic details of the ring-closure reaction and the conditions leading to side-products are discussed as well.     

Facile and Convenient Synthesis of 1‐Perfluoroalkyl‐1,2,4‐triazoles

Treatment of N‐methylcarbonyl 1, N‐phenylthioamido 2, and N‐cyano 3 iminoethers with perfluoroalkylated hydrazines leads to 1‐perfluoroalkyl‐5‐methyl‐1,2,4‐ triazoles, 4,1‐perfluoroalkyl‐5‐phenylamino‐1,2,4‐triazoles 5, and 1‐perfluoroalkyl‐5‐amino‐1,2,4‐triazoles 6 in good yields. These compounds are screened for their biological activities.     

Intramolecular Heck reaction: A facile sequential one-pot synthesis of 1,2,3,4-tetrahydrobenzo[b][1,6]naphthyridines

A simple and convenient sequential one-pot synthesis of 1,2,3,4-tetrahydrobenzo[b][1,6] naphthyridines has been developed. The reductive amination of 2-chloro-3-formylquinolines with various amines in the presence of sodium borohydride provided the corresponding secondary amines in high yields. Further, a sequential one-pot reaction involving N-allylation and intramolecular Heck type 6-exo-trig cyclization was performed on the secondary amines to afford a range of desired 1,2,3,4-tetrahydrobenzo[b][1,6]-naphthyridine derivatives in good to high yields.     

Organoboranes for synthesis : Reaction of organoboranes with representative organic azides. A general stereospecific synthesis of secondary amines and N-substituted aziridines

Reaction of trialkylboranes with organic azides in refluxing xylene, followed by hydrolysis, leads to good yields of secondary amines. This reaction is highly dependent on the steric effects around both boron and the azide moiety. The reaction becomes much slower when the steric bulk of one of the reagents is increased and fails when both are hindered. The dialkylchloroboranes are more reactive than trialkylboranes and provide better yields of the desired secondary amines with a11 azides tested. The alkyldichloroboranes react with organic azides at temperatures between room temperature and 60°C and produce excellent yields of secondary amines. Furthermore, the stereochemistry of the original carbon-boron bond is retained. The mechanism of these reactions is discussed and the reaction applied to the synthesis of N-alkyl- and N-arylaziridines.     

Redox system for perfluoroalkylation of arenes and α-methylstyrene derivatives using titanium oxide as photocatalyst

Photoirradiation of titanium oxide (TiO₂) excites the electrons from the valence band to the conduction band, leaving holes in the valence band. Using these holes and electrons, it is possible to perform one-electron oxidations and reductions. We developed a method for the photocatalytic perfluoroalkylation of aromatic rings such as benzene and its derivatives, naphthalene and benzofuran with perfluoroalkyl iodide by the combination of reduction and oxidation reactions with TiO₂. Perfluoroalkyl iodide was reduced to a perfluoroalkyl radical by the excited electrons in the conduction band of TiO₂, and the resulting radical reacted with an aromatic ring to form an arenium radical that was successively oxidized to a cation by the holes in the valence band of TiO₂. Similarly, the photocatalytic reaction of α-methylstyrene with perfluoroalkyl iodide afforded perfluoroalkylated α-methylstyrene, in which the perfluoroalkyl group is on a methyl carbon.     

Synthesis of 2,3-bis(perfluoroalkyl)quinoxalines and 2,3-bis(perfluoroalkyl)-1,4-benzoxazines from oxides of internal perfluoroolefins

The reactions of oxides of internal trans-, cis-perfluoroolefins with o-phenylenediamine and 2-aminophenol in dioxane gave 2,3-bis(perfluoroalkyl)quinoxalines and 2,3-bis(perfluoroalkyl)-2H-1,4-benzoxazin-2-ols respectively in yields of 23-67%. When N,N-dimethylacetamide was used as a solvent an anionic isomerization of the oxides into ketones, which further yielded 2-(perfluoroalkyl)benzimidazoles in the case of o-phenylenediamine and 2-hydroxy-N-perfluoroalkanoylanilines in the case of 2-aminophenol, became the main path of these reactions. Unusual cyclization resulting in 2-pentafluoroethyl-2-pentafluoropropanoylbenzoxazolidine occurs on interaction between dodecafluoro-3,4-epoxyhexane and 2-aminophenol in N,N-dimethylacetamide.     

A convenient method for the synthesis of N-hydroxyureas

Treatment of amines with 1-(4-nitrophenol)-N-(O-benzylhydroxy)carbamate yields the O-benzyl protected N-hydroxyureas. Hydrogenation of the O-benzyl protected N-hydroxyureas over 5% Pd/BaSO₄ cleanly gives the N-hydroxyureas in good yield. In addition to primary and secondary aliphatic and aromatic amines, this method converts amino sugars to the corresponding N-hydroxyureas without extensive protecting group chemistry.     

Facile N-tert-butoxycarbonylation of amines using La(NO3)3·6H2O as a mild and efficient catalyst under solvent-free conditions

Facile N-tert-butoxycarbonylation of amines is described by the treatment of various primary, secondary, benzylic and aryl amines with di-tert-butyl dicarbonate in the presence of catalytic amounts of La(NO₃)₃·6H₂O under solvent-free conditions at room temperature to afford N-tert-butylcarbamates in excellent yields.     

Platinum nanoparticles as recyclable heterogeneous catalyst for selective methylation of amines and imines with formic acid: Indirect utilization of CO2

N-methylation of amines and imines with formic acid as C1 source by easily prepared Pt NPs as heterogeneous catalyst is reported here. Primary, secondary amines and imines were successfully methylated in good to excellent yields under mild conditions. Both aromatic and aliphatic amines could be applied as substrates. Meanwhile, the heterogeneous Pt NPs were capable to be recylcled and reused for 7 times without significant decrease of reactivity. This protocol provided an indirect utilization pathway of CO₂ by using formic acid as C1 source.     

N-(2,2-Dichloro-2-phenylethylidene)arenesulfonamides in reactions with secondary amines

N-(2,2-Dichloro-2-phenylethylidene)arenesulfonamides were synthesized by a modified procedure, and their reactions with secondary amines were studied for the first time. Reactions of imines with dialkylamines proceed at room temperature to afford α,α-dichloromethylbenzene and N,N-dialkyl-N′-(arenesulfonyl)formamidines arising from the haloform cleavage of the initially formed unstable N-(1-dialkylamino-2,2-dichloro-2-phenylethyl)arenesulfonamides. When the reaction is carried out upon cooling to 0°C, the products of the nucleophilic addition of secondary amines to azomethines, N-(1-dialkylamino-2,2-dichloro-2-phenylethyl) are formed in yields of no higher than 5%. Nonempirical calculations of ¹³C-¹H spin-spin coupling constants and their experimental measurements for the series of the synthesized N-arenesulfonamides were performed to show that these compounds exist in solutions exclusively as E isomers. Preferable conformations of the investigated compounds and the relative energies of their E and Z isomers in the gas phase were determined by quantum-chemical calculations at the MP2/6-311G** level of theory. The NMR spectral data revealed restricted rotation of the N,N-dialkylamino group about the partially double C-NAlk₂ bond in the molecules of N-arenesulfonylformamidines.     

Tandem addition–cyclization of o-ethynylphenyl isothiocyanates with N nucleophiles; difference of cyclization mode between primary and secondary amines

Silver triflate promotes the 6-exo-dig mode cyclization of the N-(2-ethynylphenyl)thioureas, which were easily obtained from the o-ethynylphenyl isothiocyanates and the primary amines, to provide the 2-imino-4-methylidene-1H-benzo[d][1,3]thiazines as the sole product in excellent yields. The secondary amines reacted with the o-ethynylphenyl isothiocyanates to give both the 6-exo and 5-endo-dig mode cyclization products under the same conditions.     

Efficient synthetic protocol for substituted guanidines via copper(I)-mediated intermolecular amination of isothiourea derivatives

Amination of S-methyl-N,N′-bis-Boc-isothiourea with either primary or sterically hindered secondary amines promoted by copper(I) chloride and K₂CO₃ gave N,N′-bis-Boc protected guanidines in good to excellent yields under mild reaction conditions.