Novel synthesis of 1,4-thiazin-2-one O-(tert-butyl) oximes and benzo[b][1,4]thiazin-2-one O-(tert-butyl) oximes in the presence of K2CO3/SiO2

A simple and efficient method was developed for the synthesis of 1,4-thiazin-2-one O-(tert-butyl) oximes and benzo[b][1,4]thiazin-2-one O-(tert-butyl) oximes from N-tert-butoxy acyl imidoyl bromides and 2-aminothiols in the presence of K₂CO₃/SiO₂. Twenty five novel compounds were readily synthesized in excellent yields using this procedure. The products possessed Z-stereochemistry with regard to the CN double bond. The reaction proceeded with initial substitution of bromine in the N-tert-butoxy acyl imidoyl bromides by mercapto groups in the presence of K₂CO₃/SiO₂, and subsequent intramolecular Schiff base formation.     

Novel preparation of N-arylmethyl-N-arylmethyleneamine N-oxides from benzylic bromides with zinc and isobutyl nitrite

Treatment of benzylic bromides with Zn and LiCl, followed by the reaction with i-butyl nitrite gave N-arylmethyl-N-arylmethyleneamine N-oxides in moderate yields. The present reaction is a novel and simple method for the preparation of nitrones from benzylic bromides, although the yields are moderate.     

A simple approach to the synthesis of dialkyl 5-tert-butylamino-[2,2′]bifuranyl-3,4-dicarboxylates

Reaction of tert-butyl isocyanide with electron-deficient acetylenic esters in the presence of N¹-[(Z)-1-benzoyl-3-oxo-3-phenyl-1-propenyl]-2-(2-furyl)-2-oxoacetamide leads to dialkyl 5-tert-butylamino-[2,2′]bifuranyl-3,4-dicarboxylates in moderate yields.     

Ligand-free nickel-catalyzed Kumada couplings of aryl bromides with tert-butyl Grignard reagents

A ligand-free nickel-catalyzed Kumada cross-coupling of aryl bromides and tert-butyl Grignard reagents led to the formation of a series of tert-butyl aryls in moderate to good yields, excellent tBu/iBu ratios, and good functional group compatibility. A radical coupling process is indicated and a mechanism with a Ni(I)-Ni(III) catalytic cycle is proposed.     

Electrochemical dimerization of phenacyl bromides N-acylhydrazones—a new way to 1-N-acylamino-2,5-diaryl-pyrroles

Cathodic reduction of phenacyl bromides N-acyl hydrazones lead to dimeric 1,4-diaryl-1,4-butanedione di-N-acylhydrazones, which give the corresponding 1-N-acylamino-2,5-diarylpyrroles in good yields.     

Palladium-catalysed direct arylations of NH-free pyrrole and N-tosylpyrrole with aryl bromides

The palladium-catalysed direct coupling of aryl halides with pyrroles provides a greener access to arylated pyrroles than more classical couplings such as Suzuki, Stille or Negishi reactions. However, so far, NH-free pyrrole and N-tosylpyrrole gave disappointing results for such couplings either in terms of regioselectivity of the arylation, catalyst loading or substrate scope. The reactivity of both NH-free pyrrole and N-tosylpyrrole was studied, and the tosylated pyrrole led to higher yields of coupling products due to better conversions of the aryl bromides. A range of aryl bromides undergo regioselective coupling at C2 of N-tosylpyrrole in moderate to good yields using 1 mol % [Pd(Cl(C₃H₅)]₂ as the catalyst, KOAc as the base in DMAc.     

Copper(II) tetrafluoroborate as a novel and highly efficient catalyst for N-tert-butoxycarbonylation of amines under solvent-free conditions at room temperature

Commercially available copper(II) tetrafluoroborate hydrate was found to be a highly efficient catalyst for chemoselective N-tert-butoxycarbonylation of amines with di-tert-butyl dicarbonate under solvent-free conditions and at room temperature. Various aromatic amines were protected as their N-tert-butyl carbamates in high yields and in short times. No competitive side reactions such as isocyanate, urea, and N,N-di-t-Boc formation was observed. Chemoselective N-tert-butoxycarbonylation was achieved with substrates bearing OH and SH groups. Chiral α-amino acid esters afforded the corresponding N-t-Boc derivatives in excellent yields.     

One-pot asymmetric synthesis of α-trifluoromethylated amines from α-trifluoromethyl ketones

Diastereoselective reduction of (Rs)-N-tert-butanesulfinyl α-trifluoromethyl ketimines formed in situ from the corresponding α-trifluoromethyl ketones and N-tert-butanesulfinamide has been achieved, and either diastereomer of N-tert-butanesulfinyl α-trifluoromethyl amines was obtained in good yields with excellent diastereoselectivities (up to 99:1 dr) using NaBH₄ and L-Selectride as the reductants, respectively.     

Heck cross-coupling of vinyl heteroaromatic compounds with aryl and heteroaryl halides using Pd(II) complex under phosphine-free conditions

The palladium-catalyzed cross-coupling reaction of vinyl heteroaromatic compounds with aryl bromides and heteroaryl bromides is described using air and moisture stable N,N′,N″,O-tetrafunctional Pd catalyst under phosphine-free conditions. As a result a variety of trans-1,2-disubstituted vinyl heterocycles were obtained in high to good yields.     

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.     

Rapid Synthesis of Alkoxyamine Hydrochloride Derivatives from Alkyl Bromide and N,N′-Di-tert-butoxycarbonylhydroxylamine [(Boc)2NOH]

The conventional route to alkoxyamine hydrochloride derivatives is by reaction of alkyl bromides with N-hydroxyphthalimide or N-hydroxysuccinimide followed by addition of hydrazine and HCl. Transformation of an alkyl bromide to the corresponding alkoxyamine hydrochloride can be accomplished more rapidly in good yields without using hazardous hydrazine by reaction of (Boc)₂NOH (N,N′-di-tert-butoxycarbonylhydroxylamine) and alkyl bromide followed by addition of HCl. Alkoxyamine hydrochlorides are powerful reagents in organic synthesis that can be used to synthesize alkoxyimino derivatives after condensation with a ketone or aldehyde.     

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.     

Salen and half-salen palladium(II) complexes: synthesis, characteriztion and catalytic activity toward Suzuki-Miyaura reaction

Salen and half-salen palladium(II) complexes (salden)Pd (1, salden=N,N′-bis(3,5-di- tert-butylsalicylidene)-1,2-dimethylethylenediamine), (hsalph)PdCl (2, hsalph=3,5-di-tert- butylsalicylidene-1-iminophenylene-2-amine), and (salph)Pd (4, salph=N,N′-bis(3,5-di-tert- butylsalicylidene)-1,2-phenylenediamine) were prepared and structurally characterized by X-ray crystallography. Complex 2 proved to exhibit high catalytic activity toward Suzuki-Miyaura reaction. Polyaromatic C₃-symmetric derivatives and various fluorinated biphenyl derivatives were readily achieved in good yields using Suzuki-Miyaura reaction catalyzed by complex 2.     

An inexpensive and highly stable ligand 1,4-bis(2-hydroxy-3,5-di-tert-butylbenzyl)piperazine for Mizoroki-Heck and room temperature Suzuki-Miyaura cross-coupling reactions

A bulky, inexpensive and simple bidentate ligand 1,4-bis(2-hydroxy-3,5-di-tert-butylbenzyl)piperazine (1) has been synthesized and characterized. The palladium catalyst was formed by combination of 1 with [Cl₂Pd(COD)] in a ratio of 1:1, tested in the Suzuki-Miyaura and Mizoroki-Heck cross-coupling reactions. Coupling of a variety of aryl bromides with phenylboronic acid using methanol as solvent at room temperature, or at 60 °C, gave generally high yields of coupled products. Coupling of aryl chlorides with organoboron reagent at 110 °C in DMF afforded good yields of biaryls under aerobic conditions. This non-phosphorus, air and moisture stable catalyst also displays good activity for Mizoroki-Heck coupling reaction in methanol at 60 °C with various aryl chlorides and bromides.     

An easy route to optically active 1-substituted-1-pyridyl-methylamines by diastereoselective reduction of enantiopure N-tert-butanesulfinyl ketimines

The reduction of enantiopure N-tert-butanesulfinyl ketimines derived from pyridyl ketones afforded the related N-tert-butanesulfinyl amines with high yields and diastereoselectivities.     

Application of NO2/supercritical CO2 system for safe and selective nitration of adamantanes and tertiary alkyl bromides

A concise safe approach for selective nitration and nitroxylation of tert-alkanes, in particular adamantane, and tert-alkyl bromides utilizing NO₂ in supercritical CO₂ medium has been established. Major reaction products were tert-alkyl nitro compounds and tert-alkyl nitrates depending on the reaction conditions.     

Convenient synthesis of 1a,1b,2,5-tetrahydro-1H-5a-aza-cyclopropa[a]indenes by base promoted cyclodimerization of 1,1-dicyano-2-aryl-3-benzoylcyclopropanes

1,1-Dicyano-2-aryl-3-benzoylcyclopropanes in acetonitrile in the presence of triethylamine underwent cyclodimerization reaction to afford the novel polyfunctionalized 1a,1b,2,5-tetrahydro-1H-5a-aza-cyclopropa[a]indenes in moderate yields. These polycyclic compounds can be more conveniently synthesized by the one-pot domino reaction of N-phenacylpyridinium bromides with arylidene malononitriles.     

A practical asymmetric synthesis of ortho-substituted 4-pyrazolyl-2-ethylamines

A reliable three-step synthesis of ortho-substituted 4-pyrazolyl-2-ethylamines starting from a pyrazole methyl ketone and N-tert-butanesulfinylamine is described. Strongly dehydrating conditions were required to form the N-tert-butanesulfinyl ketimines, but these intermediates were stable to aqueous work-up and chromatography. Reduction of N-tert-butanesulfinyl ketimines with L-selectride®, or Super-hydride®, in THF afforded excellent yields and diastereoselectivities of the sulfinamides, which were converted into chiral amines with methanolic HCl. The 4-pyrazolyl-2-ethylamines from these investigations are attractive building blocks for medicinal chemists, as they exhibit low molecular weight, and low calculated octanol-water partition coefficient (c Log P values), while disrupting planarity with three-dimensional character. For example, the amine products were utilized in structure-activity studies of the human transient receptor potential vanilloid 1 (TRPV1/VR1).     

Highly diastereoselective reactions of 2-lithiated indoles with chiral N-tert-butanesulfinyl aldimines for the synthesis of chiral (2-indolyl) methanamine derivatives

Nucleophilic addition reactions of 2-lithiated N-phenylsulfonylindoles with (R)-N-tert-butanesulfinyl aldimines provided chiral (2-indolyl) methanamine derivatives in moderate to good yields (up to 100%) with excellent diastereoselectivities (>99:1), in which no additional Lewis acids were required.     

Divergent synthesis of 6H-isoindolo[2,1-a]indol-6-ones and indenoindolones: an investigation of Pd-catalyzed isocyanide insertion

A novel Pd-catalyzed intramolecular cyclization via tert-butyl isocyanide insertion from 2-(2-bromophenyl)-1H-indoles has been developed, which demonstrates the utility of isocyanides in C–N or C–C bond construction. Treatment of 2-(2-bromophenyl)-1H-indoles with tert-butyl isocyanide affords 6H-isoindolo[2,1-a]indol-6-ones with high efficiency. However, N-methyl or N-Boc protected 2-(2-bromophenyl)-1H-indoles gives indenoindolones in excellent yields under the same condition, which reveals that under the described situation, isocyanides insertion for the formation of C–N bonds is prior to that of C–C bonds.