Synthesis and aromatic nucleophilic N-N, N-S and N-O exchange reactions of N,N-dimethyl-2-trifluoroacetyl-1-naphthylamine

We succeeded in the synthesis of N,N-dimethyl-2-trifluoroacetyl-1-naphthylamine (10) by the regioselective deacylation of N,N-dimethyl-2,4-bis(trifluoroacetyl)-1-naphthylamine with trifluoroacetic acid and water. The aromatic nucleophilic substitutions of 10 with various amines, thiols and alcohols proceeded cleanly to give the corresponding N-N, N-S and N-O exchanged products in moderate to excellent yields.     

Fluorsilylsubstituierte N,N- und N,O-bis(trimethylsilyl)-hydroxylamine

Fluoro- und aminofluoro-silanes react with the lithium salt of N,O-bis(trimethylsilyl)hydroxylamine under LiF elimination and substitution. Alkyl- and amino-fluorosilanes give O-fluorosilyl-N,N-bis(trimethylsilyl)hydroxylamines, arylfluorosilanes give N-fluorosilyl-N,O-bis(trimethylsilyl)hydroxylamines. By the further reaction of O-difluorosilyl-N,N-bis(trimethylsilyl)hydroxylamine with the lithiated hydroxylamine, O,O′-fluoromethylsilyldi[N,N-bis(trimethylsilyl)hydroxylamine] is formed. On heating N-difluorophenylsilyl-N,O-bis(trimethylsilyl)hydroxylamine di[fluorophenylsilyl(methyl)amino]pentamethylsiloxane is formed by methyl group migration. The NMR and mass spectra of the compounds are reported.     

Selective N-debenzylation of amides with p-TsOH

N-Benzylamides were debenzylated efficiently with 4 equiv. of p-TsOH in refluxing toluene. Good to quantitative yields of the desired primary amides were obtained within 2-4 h from a wide variety of N-2,4-dimethoxybenzylamides. N-4-Methoxylbenzyl amides and N-benzylamides were also debenzylated cleanly. In the case of N-2,4-dimethoxylbenzylamides, selective N-debenzylation was possible in the presence of N-Fmoc, N-t-BOC or N-trityl-protection. Protected amino acid amides survived these conditions without any detectable epimerization.     

Synthesis of B-trisubstituted borazines via the rhodium-catalyzed hydroboration of alkenes with N,N′,N″-trimethyl or N,N′,N″-triethylborazine

Hydroboration of terminal and internal alkenes with N,N′,N″-trimethyl- and N,N′,N″-triethylborazine was carried out at 50 °C in the presence of a rhodium(I) catalyst. Addition of dppb or DPEphos (1 equiv.) to RhH(CO)(PPh₃)₃ gave the best catalyst for hydroboration of ethylene at 50 °C, resulting in a quantitative yield of B,B′,B″-triethyl-N,N′,N″-trimethylborazine. On the other hand, a complex prepared from (t-Bu)₃P (4 equiv.) and [Rh(coe)₂Cl]₂ gave the best yield for hydroboration of terminal or internal alkenes.     

Copper(I) catalysis: Synthesis of N,N′-diarylated and N-aryl,N′-formylated chiral C2-symmetric diamines

Chiral N,N′-diaryl C₂-symmetric diamines and N-aryl,N′-formyl-trans-(1R,2R)-diaminocyclohexane are readily accessed by copper catalyzed N,N′-diarylation and N-aryl,N′-formylation of trans-(1R,2R)-diaminocyclohexane with aryl bromides. N,N′-diarylation using (R)-1,1′-binaphthyl-2,2′-diamine and iodobenzene gave the corresponding (R)-N,N′-diphenyl-1,1′-binaphthyl-2,2′-diamine derivative in 83% yield.     

Selective functionalization at the small rim of calix[6]arene. Synthesis of novel non-symmetrical N3, N4 and N3ArO biomimetic ligands

Eight novel calix[6]arene-based biomimetic ligands for transition metal ions have been synthesized. They display a non-symmetrical N₃, N₄ or N₃ArO binding core that mimics enzyme active sites presenting histidine and tyrosine residues. The key step for their synthesis is the mono-alkylation at the small rim of the C_3v symmetrical trimethyl ether derivative of tBu-calix[6]arene with N-Boc-2-chloroethylamine to yield a novel calix[6]arene synthon. Its combined O-alkylation with a chloromethyl aromatic amine and N-deprotection or alkylation or reductive alkylation with a salicylaldehyde derivative yielded the calix[6]arene-based ligands with mixed N/O donors.     

Helicity of N,N′-diaryl-trans-1,2-diaminocyclohexane derivatives. Implications for molecular helicity manipulations

Derivatives of trans-1,2-diaminocyclohexane (DACH), useful as chiral ligands, scaffolds and building blocks, differ in their conformation. The conformation of N,N′-diaryl-DACH derivatives was studied by the semiempirical and DFT computational methods and by exciton-coupled circular dichroism. It was found that, contrary to M-helical N,N′-diimine, N,N′-diimide and N,N′-diamide derivatives, the aromatic residues in N,N′-diphenyl derivatives are oriented to form a P-helix for the (R,R)-DACH absolute configuration. The helicity of the bis-aryl system is modified in the case of 1-naphthyl or 2-naphthyl derivatives. Further switching of helicity has been demonstrated by either protonation or mono-N-acetylation of N,N′-diaryl DACH derivatives.     

Alkynylation of N-tosylimines with aryl acetylenes promoted by ZnBr2 and N,N-diisopropylethylamine in acetonitrile

We found a suitable condition for the effective alkynylation of N-tosylimines with aryl acetylenes. The reaction of N-tosylimines and aryl acetylenes in the presence of ZnBr₂ and DIEA (N,N-diisopropylethylamine) in CH₃CN afforded the desired N-tosyl propargylamines in moderate to good yields.     

Reaction of ferrocenecarboxylic acid with N,N-disubstituted carbodiimides: synthesis, spectroscopic and X-ray crystallographic analysis of N,N-disubstituted N-ferrocenoylureas and identification of a one-pot coupling reagent for the formation of ferrocenecarboxamides in a non-aqueous solvent

N,N^′-dicyclohexyl-N-ferrocenoylurea 2, N,N^′-diisopropyl-N-ferrocenoylurea 3, N,N^′-di-p-tolyl-N-ferrocenoylurea 4 and N,N^′-di-tert-butyl-N-ferrocenoylurea 5 were obtained by reaction of ferrocenecarboxylic acid 1 with N,N^′-dicyclohexylcarbodiimide (DCC), N,N^′-diisopropylcarbodiimide (DIC), N,N^′-di-p-tolylcarbodiimide 10 and N,N^′-di-tert-butylcarbodiimide 11, respectively. Both N-tert-butyl-N^′-ethyl-N-ferrocenoylurea 6 and N^′-tert-butyl-N-ethyl-N-ferrocenoylurea 7 were obtained by reaction of 1 with N-tert-butyl-N^′-ethylcarbodiimide 12. In all cases a small amount of ferrocenecarboxylic anhydride 8 was formed as a by-product. All compounds were characterized by ¹H NMR, ¹³C NMR, IR and MS. Single crystal X-ray structural analyses were made of 2, 3 and 4. From the consistent results, the reaction products of 1 with carbodiimides appear different from those proposed by some earlier workers. With N-(3-dimethylaminopropyl)-N^′-ethylcarbodiimidehydrochloride 9 ferrocenoylurea was not isolated, but the main product was rather 8. The suitability of 8 as acylation reagent was applied by using 9 to obtain N-(3-triethoxysilyl)-propylferrocenecarboxamide in a one-pot reaction from 1 and 3-(triethoxysilyl)-propylamine.     

Electrochemical fluorination of N,N-dimethylperfluoroacylamides

The electrochemical fluorination (ECF) of N,N-dimethylperfluoroacylamides gives the corresponding perfluoro-N,N-dimethylacylamides in low yield. With increase of the number of carbon atoms in the perfluoroacyl radical the yield of the required perfluoro-N,N-dimethylacylamides is slightly increased.     

N-Allyl-1,3-oxazines via a facile keto-ene/cyclization tandem reaction

The intramolecular keto-ene/cyclization tandem reaction of γ-N-allylamino ketones is an effective means of producing 1,3-oxazines. The reaction usually requires high temperatures and/or pressures. We discovered that N,N-diallyl amines undergo the reaction at lower temperatures than their monoallyl analogs. An extreme example, 1-N,N-diallylamino-9,10-anthraquinone, undergoes the keto-ene reaction near ambient temperature. In the case of 1-N,N′-dialkylaminoanthraquinones, electron deficient ene components can even be used, allowing the preparation of a broad spectrum of oxazines. Furthermore, the N-allyl-1,3-oxazine can be easily deallylated to produce a 1,3-oxazine that contains a secondary amine.     

Single-step conversion of N-benzyl, N-trityl and N-diphenylmethyl amines to t-butyl carbamates using polymethylhydrosiloxane

t-Butyl carbamates were obtained efficiently in high yields from the corresponding N-benzyl, N-trityl and N-diphenylmethyl precursors in a single-step reductive transformation employing polymethylhydrosiloxane and di-t-butyl dicarbonate under Pd(OH)₂/C catalysis.     

A short and efficient synthesis of N-aryl- and N-heteroaryl-N-(arylalkyl)piperazines

A new synthesis of N-aryl- and N-heteroaryl-N^′-(arylalkyl)piperazines using palladium-catalyzed amination of aryl bromides and heteroaryl chlorides with mono N-benzyl- or N-(arylethyl)piperazines is reported. Most coupling processes proceed in high yield and good selectivity using either diadamantyl-n-butylphosphine (1), 2-(dicyclohexylphosphino)-2^′-(N,N-dimethylamino)biphenyl (2), or 2-(di-tert-butylphosphino)biphenyl (3) as ligand. Applying an automated parallel synthesizer the preparation of a small library of potentially bioactive compounds is easily achieved.     

Pd2dba3/P(i-BuNCH2CH2)3N: a highly efficient catalyst for the one-pot synthesis of trans-4-N,N-diarylaminostilbenes and N,N-diarylaminostyrenes

A Pd₂dba₃/P(i-BuNCH₂CH₂)₃N catalyzed one-pot synthesis of unsymmetrically substituted trans-4-N,N-diarylaminostilbenes and both symmetrically and unsymmetrically substituted N,N-diarylaminostyrene derivatives is reported. The procedure involves two or more palladium catalyzed sequential coupling reactions (an amination and an inter-molecular Heck reaction) in one-pot using the same catalyst system with two different aryl halides, including aryl chlorides and hetero aryl halides as the coupling partners.     

1,n-Diamines. Part 3: Microwave-assisted synthesis of N-acyl-N′-arylhexahydropyrimidines and hexahydro-1,3-diazepines

In this Letter we present a method for the synthesis of N-acyl-N′-arylhexahydropyrimidines 1, by ring closure of N-acyl-N′-aryl-1,3-propanediamines 3 with formaldehyde. Cyclodehydrations were performed in aqueous medium under microwave irradiation, and led to high yields of the desired compounds in remarkably short reaction times. The method also allowed for the synthesis of hitherto unreported N-acyl-N′-arylhexahydro-1,3-diazepines 2. The acyclic tetramethylenic precursors 4 were synthesized by selective functionalization of N-arylputrescines.     

Efficient synthesis of N,N′-dialkyl-N″-dialkylaminocarbothioyl thioureas from cyclic secondary amines, CS2, and N,N′-dialkyl carbodiimides in water

A mild, convenient, and practical one-pot procedure for direct synthesis of N,N′-dialkyl-N″-dialkylaminocarbothioyl thioureas is described via three-component reaction of cyclic secondary amines, CS₂, and N,N′-dialkyl carbodiimides in water at room temperature.     

Enantioselective aldol reactions of trichlorosilyl enol ethers catalyzed by chiral N,N-dioxides and monodentate N-oxides

Chiral N,N^′-dioxides and monodentate N-oxides were employed as catalysts in catalytic, enantioselective aldol reactions of trichlorosilyl enol ethers. The reactions of acyclic enol ethers using N,N^′-dioxides resulted in the anti-adducts from (E)-enol ethers and the syn-adducts from (Z)-enol ethers. The reactions of cyclic (E)-enol ethers using N,N^′-dioxides gave the anti-adducts, whereas monodentate N-oxides predominantly gave the syn-adducts.     

N-(Diethoxyphosphoryl)-O-benzylhydroxylamine—a convenient substrate for the synthesis of N-substituted O-benzylhydroxylamines

Easily available N-(diethoxyphosphoryl)-O-benzylhydroxylamine was shown to be convenient, orthogonally protected substrate for regioselective N-alkylation by means of diverse halides under basic conditions (sodium hydride/tetrabutylammonium bromide). An efficient procedure for dephosphorylation of N-substituted N-(diethoxyphosphoryl)-O-benzylhydroxylamine to provide N-substituted O-benzylhydroxylamines was also established.     

A convenient and efficient method for the synthesis of mono- and N,N-disubstituted thioureas

A convenient method for the synthesis of mono- and N,N-disubstituted thioureas by the debenzoylation of N-substituted- and N,N-disubstituted-N′-benzoylthioureas with hydrazine hydrate under solvent-free conditions has been developed. N-Substituted-N′-benzoylthioureas and hydrazine hydrate were mixed, and stirred at room temperature without a solvent to give the corresponding N-substituted thioureas in high yields.