A new method for the synthesis of N-substituted 1,3,5-dithiazinanes via the catalytic recyclization of 1,3,5-trithiane with aryl(benzyl) hydrazines and aryl amines

An efficient method for the synthesis of N-substituted 1,3,5-dithiazinanes based on the amination reaction of 1,3,5-trithiane with aryl(benzyl) hydrazines and N-aryl amines in the presence of Ti and Fe catalysts has been developed.     

Diastereoselective reduction of enantiopure N-p-toluenesulfinyl ketimines derived from pyridyl ketones

DIBAL reduction of enantiopure N-p-toluenesulfinyl ketimines derived from 2-pyridyl ketones bearing an additional substituent on the 6-position of the pyridine ring afforded the related N-p-toluenesulfinyl amines with high yields and diastereoselectivities. The results of a number experiments exploring the conversion of a optically active 1-substituted N-toluenesulfinyl 1-(6-bromopyridin-2-yl)methylamine in a number of more complex pyridine derivatives with maintenance of the toluenesulfinyl group N-protecting group is also reported.     

N,N′,N″-Tri-Boc-guanidine (TBG): a common starting material for both N-alkyl guanidines and amidinoureas

In this Letter, we describe the unexpected reaction pattern of N,N′N″-tri-Boc-guanidine (TBG) with amines at room temperature and under reflux conditions affording N-substituted guanidines and amidinoureas, potentially important compounds with extensive applications in medicinal chemistry. This investigation shows that TBG is an excellent, readily available common starting material for the synthesis of various N-alkyl guanidines as well as N-alkyl-N′-substituted amidinoureas by simply manipulating the reaction conditions.     

Investigation towards an efficient synthesis of benzo[g]isoquinoline-1,5,10(2H)-triones

As part of our research on 2-aza analogues of pentalongin, the active principle of Pentas longiflora Oliv., the first synthesis of 2,3-disubstituted benzo[g]isoquinoline-1,5,10(2H)-triones via 3,4-disubstituted 6-hydroxybenzo[g]furo[4,3,2-de]isoquinoline-2,5(4H)-diones as the key intermediates is reported. The latter compounds have been prepared by treating 2-methoxycarbonyl-1,4-naphthoquinone with N-substituted enaminoesters under acidic conditions. These reagents are easily accessible from readily available 1,4-dihydroxy-2-naphthoic acid, β-ketoesters and primary amines. Finally, a short synthesis of substituted benzo[g]isoquinoline-1,5,10(2H)-triones is achieved by an oxidative addition of N-substituted enaminoesters onto methyl 1,4-dihydroxynaphthalene-2-carboxylate.     

A facile synthesis of indolo[3,2,1-jk]carbazoles via palladium-catalyzed intramolecular cyclization

A new efficient synthesis of indolo[3,2,1-jk]carbazoles by the palladium-catalyzed cyclization of N-(2-bromoaryl)carbazoles is described. The reaction involves intramolecular C-C bond formation, coupled with the cleavage of a C-X bond and a C-H bond on carbazole ring. Substitutions on N-aryl core with either electron-donating or electron-withdrawing groups are introduced, and different reaction factors for cyclization are evaluated.     

Synthesis of substituted carbazoles and β-carbolines by cyclization of diketoindole derivatives

A new route to substituted β-carbolines and carbazoles is described. Diketoindole intermediates, prepared by Friedel-Crafts acylations of 3-substituted indoles, have been converted to 3-hydroxycarbazoles and β-carbolines in good yields, 51-96% and 82-97%, respectively. This method also allows for the formation of 4-substituted β-carbolines. The application of this methodology to the synthesis of the natural products hyellazole and 6-chlorohyellazole is also described.     

Direct synthesis of N-substituted, functionalized aspartic acids using alkali maleates and amines

A practical and general one-pot synthesis of mono-N-substituted, functionalized aspartic acids has been developed. The N-substituted aspartic acids are formed directly from alkali maleates and primary amines in hot DMSO. Products from several different primary amines can be prepared chemoselectively in moderate to good yields.     

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.     

Synthesis of substituted salicylamines and dihydro-2H-1,3-benzoxazines

Phenols were converted to their magnesium salts with the MgCl₂-Et₃N base system and subsequently reacted with Eschenmoser's salt, affording N,N-dimethyl substituted benzylamines in high to excellent yields. A series of mono N-substituted benzylamines were prepared in one-pot syntheses by ortho-formylation of phenols to corresponding salicylaldehydes, which in turn reacted with amines to imines. The imines were subsequently reduced to mono N-substituted benzylamines. Some of these benzylamines were further converted, without work-up, to mono N-substituted dihydro-2H-1,3-benzoxazines.     

Synthesis of carbazoles by dehydro Diels-Alder reactions of ynamides

A new approach to carbazoles and benzannulated carbazoles by means of intramolecular dehydro Diels-Alder of ynamides is reported. N-(o-Ethynyl)aryl ynamides and N-(o-ethynyl) arylynamides were prepared in a few steps starting from o-iodoaniline. Thermal cycloaddition of N-(o-ethynyl)aryl ynamides and N-(o-ethynyl) arylynamides affords carbazoles and benzannulated and heteroannulated carbazoles in moderate-to-good yields.     

Rapid access to 3-(N-substituted)-aminoquinolin-2(1H)-ones using palladium-catalyzed C-N bond coupling reaction

A series of 3-(N-substituted)-aminoquinolin-2(1H)-ones have been synthesized by the palladium-catalyzed C-N coupling reaction starting from 3-bromoquinolin-2-(1H)-ones. Various nucleophiles including amines, amides, sulfonamides, carbamates and ureas have been used successfully. In all the cases, the reactions take place rapidly in 1,4-dioxane and proceed in good to excellent yield using palladium acetate as a catalyst, Xantphos as a ligand and Cs₂CO₃ as a base.     

On the synthesis and isolation of chlorocarbazoles obtained by chlorination of N-substituted carbazoles

Chloro derivatives of N-methylcarbazole ( 1 ), N-phenylcarbazole ( 2 ), N-acetylcarbazole ( 3 ), N-benzoylcarbazole ( 4 ) and 2-methoxy-N-methylcarbazole are synthesized. They are compounds 1a, 1b, 1c, 1d, 1e, 2a, 2b, 3a, 3b, 3c, 3d, 4a, 4b, 5a, 5b, 5c, 5d and 5e . Some of them are described for the first time. By using semiempirical PM3 method theoretical substituent effects on the chlorinating reaction are calculated. A chlorination mechanism of carbazoles and N-substituted carbazoles are compared.     

Efficient one-pot formation of 4-N-substituted 2,4-dihydro-3H-1,2,4-triazolin-3-ones from primary amines using N′-(ethoxymethylene)hydrazinecarboxylic acid methyl ester

(E)-N′-(Ethoxymethylene)hydrazinecarboxylic acid methyl ester was synthesized in one step in good yield. This reagent was successfully applied to the one-pot synthesis of 4-substituted 2,4-dihydro-3H-1,2,4-triazolin-3-ones from readily available primary alkyl and aryl amines. This reaction process is relatively mild and easy to carry out. It is especially useful for the formation of sterically hindered triazolinones, which are otherwise difficult to obtain via existing literature procedures. A possible mechanistic pathway for the transformation is outlined.     

Synthesis of meso-tetraphenyl porphyrins via condensation of dipyrromethanes with N-tosyl imines

A new synthetic route for the synthesis of 5,10,15,20-tetraphenyl porphyrins has been developed based on the reaction of 5-substituted dipyrromethanes with N-tosyl imines in the presence of a metal triflate catalyst. meso-Substituted tetraphenyl porphyrins were synthesized in a two-step process. The first step of the method is the metal triflate-catalyzed condensation of 5-substituted dipyrromethanes with N-tosyl imines to form a porphyrinogen intermediate and the second step is the oxidation of the porphyrinogen to porphyrin. The method was applied to the synthesis of trans-A₂B₂-tetraarylporphyrins and the products were obtained with only a trace amount of one scrambling product. The synthesis of two important building blocks for porphyrin synthesis, mono and di-sulfonamide alkylated 5-substituted dipyrromethanes, was achieved by the addition of 5-substituted dipyrromethane to N-tosyl imine. The application of mono and di-sulfonamide alkylated 5-substituted dipyrromethanes in ‘2+2’ porphyrin formation reactions is presented.     

Reaction of N-Fmoc aspartic anhydride with glycosylamines: a simple entry to N-glycosyl asparagines

The reaction of N-Fmoc-aspartic anhydride with glycosyl amines in DMSO selectively leads to the formation of β-substituted products, thus providing a simple and efficient route to N-glycosyl asparagine derivatives, the building blocks for glycopeptide synthesis.     

Ruthenium trichloride catalyzed synthesis of 2,3-unsaturated-N-glycosides via Ferrier azaglycosylation

An efficient, economical and mild protocol for the synthesis of 2,3-unsaturated-N-glycosides has been developed using ruthenium(III) chloride. The Ferrier azaglycosylation of glycals with various N-nucleophiles such as sulfonamides, benzamides, carbamates and N-substituted sulfonamides proceeded smoothly to afford the corresponding 2,3-unsaturated-N-glycosides or ‘N-pseudoglycals’ in good yields (64–98%). High α-anomeric selectivity was observed with N-substituted sulfonamides such as N-benzyl or N-phenyl sulfonamides under similar conditions.     

Arylation of adamantanamines: VI. Palladium-catalyzed arylation of amines and diamines of the adamantane series with 3-bromopyridine

Palladium-catalyzed amination of 3-bromopyridine with amines of the adamantane series in the presence of Pd(dba)₂/L [L = 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl or 2-dimethylamino-2′-dicyclohexylphosphinobiphenyl] gave the desired N-(pyridin-3-yl)-substituted amines in 74–97% yields. Diamines of the adamantane series reacted with 2 equiv of 3-bromopyridine in a complicated fashion to produce mono- and triaryl-substituted derivatives as by-products, while the yields of N,N′-diarylation products were 18–56%.     

Recent advances in the synthesis of N-alkenyl carbazoles

N-Alkenyl carbazoles are important building blocks of poly(vinylcarbazole), which is used in photosensitive materials, semiconductors, electroluminescent devices, and non-linear optical materials. Recently, a CN bond formation reaction using transition-metal-catalyzed amination and transition-metal-catalyzed vinylation was successfully extended to the synthesis of N-alkenyl carbazoles. In this paper, I discuss recent examples of the synthesis of N-alkenyl carbazoles, including palladium and copper-catalyzed cross-coupling reactions of carbazoles with alkenes/alkenyl halides, and iridium-catalyzed vinylation of carbazole using vinyl acetate.     

High regioselectivity in electrochemical α-methoxylation of N-protected cyclic amines

N-Protecting groups of α-substituted cyclic amines strongly affected the regioselectivity in electrochemical methoxylation of these compounds. Namely, N-acyl derivatives were transformed into α′-methoxylated compounds, while N-cyano derivatives changed into α-methoxylated derivatives. Furthermore, Lewis acid catalyzed nucleophilic substitution of the α-methoxylated compounds protected with cyano group afforded α,α-disubstituted cyclic amines.     

TfOH catalyzed synthesis of 1-substituted tetrahydrocarbazoles

Synthesis of 1-substituted tetrahydrocarbazole is accomplished by TfOH catalyzed reaction of 3-substituted indoles tethered with secondary and tertiary alcohols. The reaction was generalized for a variety of substrates and was extended to the synthesis of 2,3,3a,6-tetrahydro-1H-pyrido[3,2,1-jk]carbazole and carbazoles.