Stereoselective synthesis of cis and trans-fused 3a-aryloctahydroindoles using cyclization of N-vinylic α-(methylthio)acetamides: synthesis of (−)-mesembrane

Treatment of N-(2-arylcyclohex-1-en-1-yl)-α-(methylthio)acetamides with N-chlorosuccinimide (NCS) gave 3a-aryl-2,3,3a,4,5,6-hexahydro-3-(methylthio)indol-2-ones. Desulfurization of the cyclization products followed by a catalytic hydrogenation of the resulting hexahydroindol-2-ones gave predominantly or exclusively trans-fused octahydroindol-2-ones. On the other hand, reduction of the desulfurization products with Et₃SiH in CF₃CO₂H exclusively provided cis-fused octahydroindol-2-ones. A chiral induction of N-[2-(3,4-dimethoxy)phenylcyclohex-1-en-1-yl]-α-(methylthio)acetamide having an (R)-1-(1-naphthyl)ethyl group on the nitrogen atom led to the synthesis of (−)-mesembrane and (−)-trans-mesembrane.     

Superelectrophilic activation of N-aryl amides of 3-arylpropynoic acids: synthesis of quinolin-2(1H)-one derivatives

The superelectrophilic activation of N-aryl amides of 3-arylpropynoic acids by Bronsted superacids (CF₃SO₃H, HSO₃F) or strong Lewis acids AlX₃ (X=Cl, Br) results in the formation of 4-aryl quinolin-2(1H)-ones in quantitative yields. The vinyl triflates or vinyl chlorides may be formed as additional reaction products. The investigated amides in reactions with benzene give 4,4-diaryl 3,4-dihydroquinolin-2-(1H)-ones under the superelectrophilic activation. 4-Aryl quinolin-2(1H)-ones in POCl₃ are converted into 4-aryl 2-chloroquinolines. 4-Fluorophenyl-4-phenyl 3,4-dihydroquinolin-2-(1H)-one give N-formylation products in a yield of 79% under the Vilsmeier–Haack reaction conditions.     

N-[1-(Benzotriazol-1-yl)alkyl]amides from N-acyl-α-amino acids or N-alkylamides

A variety of N-(1-methoxyalkyl)amides react with benzotriazole in the presence of PPh₃·HBF₄ and organic bases (Hünig's base, DBU or DABCO) or solid-state-supported bases (SiO₂-Pip or IRA-67) in CHCl₃ to give N-[1-(benzotriazol-1-yl)alkyl]amides in good yields. The most convenient and efficient procedure for obtaining N-[1-(benzotriazol-1-yl)alkyl]amides consists, however, of the addition of benzotriazole sodium salt to a solution of crude 1-(N-acylamino)alkyltriphenylphosphonium salt, obtained in situ from N-(1-methoxyalkyl)amides and PPh₃·HBF₄. A combination of these reactions with the recently described electrochemical decarboxylative α-methoxylation of N-acyl-α-amino acids in the presence of SiO₂-Pip enables an effective two-pot transformation of N-acyl-α-amino acids to N-[1-(benzotriazol-1-yl)alkyl]amides.     

Base promoted facile route to functionalized benzo[b][1,8]naphthyridin-2-(1H)-ones from N-benzyl-N-(3-cyanoquinolin-2-yl)acetamides

A facile synthesis of 4-amino-N-benzylbenzo[b][1,8]naphthyridin-2(1H)-ones 3 is described from N-benzyl-N-(3-cyanoquinolin-2-yl)acetamides 2 with t-BuOK in excellent yields in mild conditions. These reactions proceeded at room temperature under aerobic atmosphere in very short period. The cyclization reactions were also extended with N-alkyl amino acetamide analogues affording the products in good yields.     

Unexpected course of rearrangement of substituted S-(1(3H)-isobenzofuranone-3-yl)isothiuronium bromides

Three series of S-(1(3H)-isobenzofuranone-3-yl)isothiuronium bromides differing in substitution at the isothiuronium moiety (none, one or two methyl groups) and at the benzene ring were prepared and characterized. These salts were then treated with various bases (acetate, triethylamine, Na₂CO₃) to give either 1-hydroxy-3-oxo-1,3-dihydro-2H-isoindol-2-carbothioamides or the product of S to N isobenzofuranone-3-yl migration, i.e., 1,3-dimethyl-1-(3-oxo-1,3-dihydro-2-benzofuran-1-yl)thioureas. If ammonia was used in reaction with N,N′-dimethyl isothiuronium salts then 3-hydroxy-2,3-dihydro-1H-isoindol-1-ones were formed together with 1,3-dimethyl-1-(3-oxo-1,3-dihydro-2-benzofuran-1-yl)thioureas in parallel reaction with the yields increasing with ammonia concentration. The formation of isoindolones takes place in two steps with an aldehyde intermediate, which can be trapped with N,N-dimethylhydrazine.     

Stereoselective radical cyclizations of N-(2-halobenzoyl)-cyclic ketene-N,X(X=O, S)-acetals

2-Alkyloxazolines and 2-alkylthiazolines react with 2-halobenzoyl chlorides to form N-(2-halobenzoyl)-cyclic ketene-N,O-acetals and N-(2-halobenzoyl)-cyclic ketene-N,S-acetals in excellent yields, respectively. These ketene acetals readily undergo stereocontrolled aryl radical cyclizations to afford the central six-membered rings of substituted-2,3,10,10α-tetrahydrooxazolo[3,2-b]isoquinolin-5-ones and their 2,3,10,10α-tetrahydrothiazolo[3,2-b]isoquinolin-5-one analogs. The tertiary N,O- and N,S-radicals formed upon aryl radical reaction at the ketene-N,X(X=O, S)-acetal double bond appear to have reasonable stability. The stereoselectivity in hydrogen abstractions by these intermediate radicals from both Bu₃SnH and (Me₃Si)₃SiH was investigated. The N,S-heterocyclic fused ring products may have potential medical value.     

Thermolysis of 1-phthalimidoaziridine-2-carbonitriles in the presence of dipolarophiles

Thermolysis of trans-3-phenyl-1-phthalimidoaziridine-2-carbonitrile and trans-1-phthalimidoaziridine-2,3-dicarbonitrile in the presence of several dipolarophiles involves 1,3-dipolar cycloaddition to intermediate azomethine ylides and leads to 1-phthalimidopyrrolidine derivatives with good yields and high stereoselectivity. Thermally induced opening of the three-membered ring in trans-2,3-disubstituted 1-phthalimidoaziridines occurs in conrotatory mode to produce the corresponding cis-azomethine ylides in keeping with the orbital symmetry conservation rules. The relative configuration of substituents in the dipolarophiles is retained, which implies concerted mechanism of the addition.     

A one-pot synthesis and mild cleavage of 2-[2- or 5-(alkylsulfanyl)pyrrol-1-yl]ethyl vinyl ethers by t-BuOK/DMSO: a novel and facile approach to N-vinylpyrroles

Substituted N-[2-(vinyloxy)ethyl]pyrroles, prepared in good yield through an allenic or acetylenic carbanion/isothiocyanate one-pot methodology from 2-(vinyloxy)ethyl isothiocyanate and allyloxyallene, methoxyallene, N,N-dimethyl-2-propyn-1-amine, and 3-methoxy-1-(methylsulfanyl)-1-propyne, are smoothly converted into the corresponding N-vinylpyrroles using t-BuOK/DMSO (room temperature). The reaction proceeds via elimination of vinyl alcohol from the N-[2-(vinyloxy)ethyl] substituent and represents a novel approach to N-vinylpyrroles.     

Regioselective synthesis of substituted 1-indanols, 2,3-dihydrobenzofurans and 2,3-dihydroindoles by electrochemical radical cyclization using an arene mediator

Electrochemical reduction of haloarenes carrying 2-(1-hydroxybut-3-enyl), 2-allyloxy or N-allyl-N-methylamino group in the presence of phenanthrene as a mediator generated the corresponding aryl radicals and gave the corresponding 5-exo cyclization products in good yields. Higher regio- and stereoselectivities than those of usual radical cyclization using AIBN-Bu₃SnH were achieved.     

Diastereoselective formation of 2-fluoro-2-trifluoromethyl-3,4-alkadienamides from propargyl alcohols and hexafluoropropene-diethylamine adduct (PPDA)

Treatment of propargyl alcohols (1) with hexafluoropropene-diethylamine adduct (PPDA) affords N,N-diethyl-2-fluoro-2-trifluoromethyl-3,4-alkadienamides (2) that are produced by the Claisen rearrangement of intermediary 2-alkynyl 1-(N,N-diethylamino)-2,3,3,3-tetrafluoro-1-propenyl ethers. Starting from propargyl alcohols bearing a triple bond at the terminal position, the corresponding products (2) were formed with a high stereoselectivity.     

Synthesis of the end-capped 5-(N,N-dimethylamino)naphthyl-1-ethynyl derivatives and their 1,4-di[5-(N,N-dimethylamino)naphthyl]-1,3-butadiynes: anti rotamer structure

A new family of the end-capped 5-(N,N-dimethylamino)naphthylethynyl chains were synthesized, as terminal acetylenes or poly(yne) structures, by heterocoupling between 5-iodo-N,N-dimethylnaphthalen-1-amine and 2-methyl-3-butyn-2-ol or 4-(5-iodo-1-naphthyl)-2-methyl-3-butyn-2-ol, catalyzed by the palladium-copper system. Catalytic homocoupling of the terminal acetylenes, affords to 1,4-dinaphthyl-1,3-butadiyne nanostructures. X-ray diffraction analysis of 1,4-di(α-naphthyl)-1,3-butadiyne shows that the naphthalene rings are in the anti configuration along the acetylene axis. All the conjugated compounds show an important fluorescent emission radiation.     

Acyclic tertiary diamines and 1,4,7,10-tetraazacyclododecane with fluorine-containing β-diketones: Leading to low melting ionic adducts

N,N,N′,N′-Tetramethylmethanediamine (1a), N,N,N′,N′-tetramethylethanediamine (1b), N,N,N′,N′-tetramethyl-1,3-propanediamine (1c), and N,N,N′,N′-tetramethyl-1,6-hexanediamine (1d) were reacted at 25 °C with 1,1,1,5,5,5-hexafluoro-2,4-pentanedione (2a), 2,2-dimethyl-6,6,7,7,8,8,8-heptafluoro-3,5-octanedione (2b), 2-thenoyltrifluoroacetone (2c), and 4,4,4-trifluoro-1-(2-furyl)-1,3-butanedione (2d) to form the ionic adducts 3-18. 1,4,7,10-Tetraazacyclododecane (1e) reacted at 25 °C with β-diketones (2a-d) and 1,1,1-trifluoro-2,4-pentanedione (2e) to give ionic solids 19-23 in good yields. Some of the products are liquid at 25 °C and are thermally stable over long liquid ranges as determined by thermal gravimetric analyses. Single-crystal X-ray structure determinations show that compounds 9 and 21 crystallize in the monoclinic space groups P2(1)/c and P2(1)/n, respectively. All the new compounds were characterized by ¹H, ¹⁹F and ¹³C NMR, electrospray MS and/or elemental analyses.     

Synthesis of a new series of ditopic proligands for metal salts: differing regiochemistry of electrophilic attack at 3{5}-amino-5{3}-(pyrid-2-yl)-1H-pyrazole

An improved synthesis of 3{5}-amino-5{3}-(pyrid-2-yl)-1H-pyrazole (I) is described, which affords the compound on a multi-gram scale. Reaction of I with acid chloride and isothiocyanate electrophiles in MeCN cleanly results in attack at its amino group, yielding N-(3-{pyrid-2-yl}-1H-pyrazol-5-yl)amide and N-(3-{pyrid-2-yl}-1H-pyrazol-5-yl)thiourea products. These are good candidates as proligands for the simultaneous complexation of metal cations and anions. However, treatment of I with isocyanates under the same conditions instead yields attack at the pyrazole ring, giving 3-(pyridin-2-yl)-5-aminopyrazole-1-carboxylic acid amides as the only isolable products. The differing regiochemistries of these reactions were confirmed by ¹H NMR and X-ray crystallography.     

1-(N-Acylamino)alkyltriphenylphosphonium salts as synthetic equivalents of N-acylimines and new effective α-amidoalkylating agents

1-(N-Acylaminoalkyl)triphenylphosphonium salts 2a-f on reaction with DBU in MeCN are transformed into 1-(N-acylaminoalkyl)amidinium salts 3a-f. Amidinium salts 3d-f with a proton at the β-position undergo slow tautomerization into the corresponding enamides 6d-f. The same 1-(N-acylamino)alkyltriphenylphosphonium salts 2d-f in the presence of Hünig’s base are transformed directly into the corresponding enamides. Phosphonium salts 2, amidinium salts 3, and enamides 6 react with dialkyl malonates in the presence of DBU to give the corresponding amidoalkylation products. α-Amidoalkylation of dialkyl malonates is not observed in the presence of (i-Pr)₂EtN, yet proceeds well under these conditions with more acidic nucleophiles, for example, phthalimide or benzyl mercaptan.     

Synthesis and optical properties of conjugated N,N-dimethyl and thienyl end-capped 2,5-(arylethynyl)thiophene oligomer structures

End-capped (N,N-dimethylaminophenyl) and 2′-thienylethynyl 2,5-thiophene oligomer structures were synthesized by heterocoupling between the terminal acetylenes such as: p-(N,N-dimethylaminophenyl)ethyne (3) [or 1-(p-(N,N-dimethylaminophenyl)-2-p-(ethynylphenyl)ethyne, 4]; p-(β-ethenyl-2′-thienyl)phenylethyne (E-9) [or p-(β-ethynyl-2′-thienyl)phenylethyne, 11], and 2,5-diiodothiophene, catalyzed by the Cl₂Pd(PPh₃)₂/CuI system, in good to excellent yields. The 2,5-di[(3′,5′-di(trimethylsilylethynyl)phenyl]_x-1-ethynyl]thiophene oligomers were prepared by heterocoupling between 3′,5′-di[(trimethylsilylethynyl)phenyl]_x-1-ethyne (n = 0-2) terminal acetylenes and 2,5-diiodothiophene, in excellent yields. The terminal acetylenes were efficiently prepared by a specific protection-deprotection methodology. All the ethynylphenyl compounds obtained show fluorescence radiation emission, with a bathochromic shift of the wavelength that increases with the chain conjugation.     

A novel and facile synthesis of mesoionic 1,2,4-triazolium-3-thiolate derivatives

Mesoionic 1,2,4-triazolium-3-thiolate derivatives were synthesized from the reaction of N-substituted-2-phenylhydrazinocarbothioamides with tetracyanoethylene (TCNE) to give tricyanovinyl intermediates, followed by heterocyclization to afford 5-(1-amino-2,2-dicyano-vinyl)-4-substituted-1-phenyl-4H-1,2,4-triazol-1-ium-3-thiolates in 67–76% yields. The structures of the products have been confirmed unambiguously by single crystal X-ray structure analyses. A rationale for the formation of the products is presented.     

DFT study of the reaction sites of N,N′-substituted p-phenylenediamine antioxidants

The geometry of N,N′-diphenyl-p-phenylenediamine (DPPD), N-phenyl-N′-(1′-methylbenzyl)-p-phenylenediamine (SPPD), N-phenyl-N′-(1,3-dimethyl-butyl)-p-phenylenediamine (6PPD), N-phenyl-N′-isopropyl-p-phenylenediamine (IPPD), and N-(1-methyl-1-phenylethyl)-N′-phenyl-p-phenylenediamine (CPPD) as well as of their dehydrogenation products has been optimized at B3LYP/6-31G^∗ level of theory. Our results support the idea of formation of stable ketimine Ph-NC structures (instead of quinonediimine structures) during consecutive dehydrogenation of SPPD, 6PPD, and IPPD antioxidants despite the formation of tertiary carbon-centered radicals in the first dehydrogenation step is energetically preferred for SPPD only.     

A facile synthesis of 2-[1-(dialkylamino)alkyl]-4H-3,1-benzoxazin-4-ones by the reaction of 1,1-dimethylethyl 2-isocyanobenzoates with N,N-dialkyliminium iodides

A convenient synthetic approach to 2-[1-(dialkylamino)alkyl]-4H-3,1-benzoxazin-4-ones has been developed. Thus, 1,1-dimethylethyl 2-isocyanobenzoates, which can be readily prepared from 2-nitrobenzoic acids by a simple four-step sequence, react with N,N-dialkyliminium iodides without using any catalysts under mild conditions to give the desired products in generally fair-to-good yields.     

Nucleophilic addition of regioselectively lithiated indoline with aldimines for the syntheses of 2- and 7-indolinyl methanamine derivatives

Indolines bearing different N-protecting groups (N-Tbf and N-Boc) were deprotonated regioselectively at C-2 (sp³ hybridized ortho-H) and C-7 (sp² hybridized para-H) of the indoline ring, respectively. The generated organolithium intermediates reacted with aldimines to give the desired products in good yields with excellent anti-diastereoselectivities (>99:1). The produced N-Ts-(1-Tbf-indolin-2-yl)methanamine was facilely transformed to a fused heterocyclic compound.     

Novel generation of selenoaldehydes through stannic chloride-induced unsymmetrical C-Se bond cleavage of bis(N,N-dimethylcarbamoylseleno)methanes

Treatment of a benzene or a CH₂Cl₂ solution of bis(N,N-dimethylcarbamoylseleno)methanes with SnCl₄ afforded β-1,3,5-triselenanes, and the key intermediates, acylselonium ions and selenoaldehydes, were successfully trapped by using allyltrimethylsilane or 2,3-dimethyl-1,3-butadiene to obtain the allylation products or the cycloadducts, respectively.