Fused isoquinolines: 3-aryl-2,3,4,5-tetrahydro-1H-pyrrolo[2,3-c]isoquinoline-1,5-dione-2-spiro-4′-(1′-alkyl-1′,4′-dihydropyridine)s

Previously unknown 3-arylamino-1,2-dihydro-1-isoquinolones were obtained by condensation of 2-cyanomethylbenzoic acid with arylamines. Isonicotinoylation of the compounds was shown to proceed at the carbon atom in the 4-position to give 3-arylamino-4-isonicotinoyl-1,2-dihydro-1-isoquinolones which were quaternized with alkylating agents and formed the corresponding pyridinium salts. Deprotonation of the latter induced intramolecular conjugated addition with the pyrrole ring closure and formation of spiro compounds. The structure of the products was confirmed by NMR, IR and UV spectroscopy and by synthesis of the model compound, 3-(4-tolyl)-2,3,4,5-tetrahydro-1H-pyrrolo[2,3-c]isoquinoline-1,5-dione.     

Synthesis of 1′-aryl-2′-(2-oxoindolin-3-yl)spiro[indoline-3,5′-pyrroline]-2,3′-dione via one-pot reaction of arylamines, acetone, and isatins

An efficient synthetic method for 1′-aryl-2′-(2-oxoindolin-3-yl)spiro[indoline-3,5′-pyrroline]-2,3′-diones was successfully developed via the one-pot domino reaction of arylamines, acetone, and isatins in acetic acid. The reaction mechanism involved the sequential Michael addition and ring closure of the in situ formed 3-N-aryliminoisatin and isatylidene acetone.     

Chemistry of N-functionalized spirodihydroquinolines. Unusual access to the 3-methyl-4-(2-oxo-pyrrolidinyl-1)spiro[indane-1,1′-cyclohexanes] from 1-(3-cyanopropyl)-3,4-dihydrospiro[quinoline-2,1′-cyclohexanes]

The transformation of N-substituted 3,4-dihydrospiro[quinoline-2,1′-cyclohexanes] 2 and 3 has been examined in strong acid media, at elevated temperature. It was demonstrated that the N-(γ-cyanopropyl) spirodihydroquinolines 2 in the presence of concentrated sulfuric acid or PPA underwent hydrolysis affording the γ-aminoacids 3. The spirodihydroquinoline ring rearrangement readily produces 4-(2-oxopyrrolidinyl-1)spiro[indane-1,1′-cyclohexanes] 5 in good yields. The structures of all synthesized compounds were established by means of homonuclear and inverse-detected 2D NMR experiments.     

Synthesis of spiro[4.5]decane and bicyclo[4.3.0]nonane ring systems by self-cyclization of (Z)- and (E)-2-(trimethylsilylmethyl)pentadienal derivative

The two title carbon frameworks were synthesized utilizing a new type of iron-induced cyclization reaction of 2-(trimethylsilylmethyl)pentadienal. 2-Methylspiro[4.5]dec-2-en-1-one was obtained from (Z)- and (E)-4-cyclohexylidene-2-(trimethylsilylmethyl)but-2-enal. It was found that the (Z)-substrate isomerized to (E)-intermediate followed by cyclization to afford the initial product, 2-methylenespiro[4.5]dec-3-en-1-ol, which was isomerized to the above product. The cyclization of 4-(4-alkyl)cyclohexylidene-2-(trimethylsilylmethyl)but-2-enal proceeded stereoselectively. While, (E)-3-(cyclohex-1-en-1-yl)-2-(trimethylsilylmethyl)prop-2-en-1-al cyclized immediately affording 8-methylenebicyclo[4.3.0]non-9-en-7-ol. The corresponding (Z)-isomer gave several cyclization products as a complex mixture.     

Rearrangements initiated by trimethylsilyl iodide: ready deoxygenative rearrangement of bicyclo[4.2.0]octane-2,5-diones to bicyclo[3.3.0]oct-1(5)-en-2-ones

Reaction of bicyclo[4.2.0]octane-2,5-diones with trimethylsilyl iodide gave bicyclo[3.3.0]oct-1(5)-en-2-ones by a clean reductive rearrangement in good yields, providing a simple and effecient synthetic method for the enones.     

Spontaneous cyclization of (acridin-9-ylmethyl)thioureas to spiro [dihydroacridine-9′(10′H),5-imidazolidine]-2-thiones,a novel type of acridine spirocycles

Novel acridine spirocompounds, spiro[dihydroacridine-9′(10′H),5-imidazolidine]-2-thiones have been prepared by the spontaneous cyclization of 1-substituted 3-(acridin-9-ylmethyl)thioureas, which were obtained from 1-(acridin-9-yl)methanamine, N-(acridin-9-ylmethyl)propan-1-amine, and N-(acridin-9-ylmethyl)benzylamine and alkyl/aryl isothiocyanates, as continuation of our previous studies on new acridine spirocycles. Imidazolidine-2-thiones thus obtained were subsequently transformed with mesitylnitrile oxide to imidazolidine-2-one analogues, some of which partly reopened to the corresponding (acridin-9-ylmethyl)ureas. An unusual spirocyclization via a CH carbanion instead of the N-1 nitrogen has been found for 3-(acridin-9-ylmethyl)-1-(acridin-9-yl)thioureas possessing two acridine rings. Structural modifications in positions 1, 3, and 4 of the spiro ring together with ¹H, ¹³C, and ¹⁵N NMR spectroscopy and X-ray crystallography have been employed to rationalize a general propensity of various 9-substituted acridines to undergo easy spirocyclization.     

Thiomethylmagnesium Chlorides: Synthesis via Hg–Mg Transmetallation and Crystallization of a Grignard Compound as 1/1 Adduct of [Mg(CH2SPh)2(thf)3] and [MgCl2(thf)4]

Thiomethylmercury chlorides 2 Hg(CH₂SMe)Cl · HgCl₂ and Hg(CH₂SPh)Cl react with magnesium in thf to give the Grignard compounds Mg(CH₂SR)Cl (R = Me ( 1 ), Ph ( 2 )) in nearly quantitative yields. From thf/n‐hexane solutions of 2 precipitate at –40 °C colorless crystals of the composition Mg(CH₂SPh)Cl · 3.5 thf ( 2 ′). X‐ray structure determination revealed, that the unit cell contains separated molecules of [Mg(CH₂SPh)₂(thf)₃] and [MgCl₂(thf)₄]. In the [Mg(CH₂SPh)₂(thf)₃] molecules magnesium is distorted trigonal‐bipyramidally coordinate. Two PhSCH₂ and one thf ligand occupy the equatorial positions and two further thf ligands the apical ones. In the [MgCl₂(thf)₄] molecules Mg displays an octahedral coordination with chloro ligands in mutual trans position. Temperature dependent NMR measurements of 2 reveal that in thf the Schlenk equilibrium operates; the composition of the equilibrium mixture at room temperature was estimated to be 89% Mg(CH₂SPh)Cl and 11% Mg(CH₂SPh)₂.     

Synthesis and biological activity of the metabolites of N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-2-nitroaniline fumarate (SK-946).

Three metabolites of N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-2-nitroaniline fumarate (SK-946), a novel central muscarinic cholinergic receptor agonist, were prepared to confirm their proposed structures, and tested for muscarinic receptor affinity in vitro.     

Synthesis of (±)-6-oxa-3-azabicyclo[3.1.1]heptan-2-thione: a potential synthon for the preparation of novel heteroaryl-annulated bicyclic morpholines

The novel bridged bicyclic morpholinethione (±)-6-oxa-3-azabicyclo[3.1.1]heptan-2-thione (9) has been prepared in six steps. This conformationally restricted morpholinethione was prepared stereoselectively using straightforward chemistry and inexpensive starting materials. The key oxetane ring was formed via an intramolecular alkylation reaction.     

Asymmetric route to spirotetracyclic (1S)-5′,11′-dihydro-3H-spiro[cyclopentane-1,10′-dibenzo[a,d]cyclohepten]-3-one derivatives

A new synthetic pathway to the final compound 1-[(1S)-5’,11’-dihydrospiro[cyclopentane-1,10’-dibenzo[a,d]cyclohepten]-3-yl]-3-azetidinecarboxylic acid (1) was set up. The two preparative chiral HPLC separations needed in the first route were successfully avoided and replaced by two diastereomeric crystallizations of intermediate compounds 5 and 10.     

Perhydroxylated 1,7-Dioxaspiro[5.5]undecanes (“Spiro Sugars”): Synthesis,Stereochemistry, and Structure

As spiro sugars is an apt way of considering perhydroxylated 1,7-dioxaspiro[5.5]undecanes–a class of compounds which has not been found in nature up to now. The crystal structure of such a spiroacetal, in which the two pyran rings show the β-D -manno configuration, is depicted. Note that the all-trans arrangement of C-6, C,-5, O_pyr, C_spiro, O_pyr^′, C-5′, and C-6′ does not allow any of the stereoelectronic effects that are typical of carbohydrates.     

Synthesis and separation of the atropisomers of 2-(5-benzo[b]fluorenyl)-2′-hydroxy-1,1′-binaphthyl and related compounds

Several syn and anti atropisomers of 2-(5-benzo[b]fluorenyl)-2′-hydroxy-1,1′-binaphthyl and related compounds were synthesized from 1,1′-binaphthyl-2,2′-diol (BINOL). It was possible to separate the syn and anti atropisomers by silica gel column chromatography. The syn atropisomers are potential hetero-bidentate ligands for complex formation with metals. By starting from enantiomerically pure (R)-(+)-BINOL and (S)-(−)-BINOL, four optically active syn atropisomers and two anti atropisomers with high enantiomeric purity were obtained. The structures of two syn atropisomers and one anti atropisomer were established by X-ray structure analyses.     

BINOL-phosphoric acids-catalyzed furylogous pinacol rearrangement of 1-[5-(hydroxy-diaryl-methyl)-furan-2-yl]-cyclobutanols into spiro cyclopentanones

A BINOL-phosphoric acid-catalyzed furylogous Pinacol rearrangement is developed. This reaction produces spiro cyclopentanone in good yields under mild conditions. The enantioselective version of this reaction is also investigated using chiral phosphoric acid (CPA) as the catalyst.     

Synthesis, properties and molecular structure of a novel dicyanoheptafulvene derivative, 4′-dicyanomethylidenedispiro[cyclohexane-1, 1′-(1′,4′,7′-trihydrocyclopenta[f]azulene)-7′,1″-cyclohexane]

A novel dicyanoheptafulvene 9 annulated by two spiro[4,5]deca-1,3-dienes was synthesized by the reaction of dispirocyclopentaazulenium cation 8 with bromomalononitrile. Although 9 was found to have a nonplanar heptafulvene structure by its X-ray crystallographic analysis, it is still capable of π-conjugation and thus shows appreciable contribution of the dipolar resonance form 9B based on its spectroscopic data. The degree of the contribution was further evaluated for various dicyanoheptafulvenes in terms of the partial sum of atomic charges of the dicyanomethylene group in the calculated structures besides the interplanar angles of the heptafulvene part and the length of the exocyclic double bond in the crystal structures.     

Intramolecularly donor-stabilized silenes: Part 5. Generation and conversion of 1-[2,6-bis(alkoxymethyl)phenyl]- and 1-(8-alkoxynaphthyl)-1,2,2-tris(trimethylsilyl)silenes

1-(8-Methoxy-1-naphthyl)-1,2,2-tris(trimethylsilyl)silene (10) and the 1-[2,6-bis(alkoxymethyl)phenyl]-1,2,2-tris(trimethylsilyl)silenes (12a-d) were generated by the reaction of (dichloromethyl)tris(trimethylsilyl)silane (1) with two molar equivalents of 8-methoxy-1-naphthyllithium or 2,6-bis(alkoxymethyl)phenyllithium (8a-d), respectively, but proved to be unstable. 10 was trapped with excess of the applied naphthyllithium reagent to give 1,1-bis(8-methoxy-1-naphthyl)-1-[bis(trimethylsilyl)methyl]-2,2,2-trimethyldisilane (11); and 12a-d underwent spontaneous conversions and formed two types of substituted 2-oxa-1-silaindane derivatives (13a,b and 14b-d). Whereas silenes with an intramolecular amine coordination are thermally stable compounds which can be isolated, the intramolecular coordination of an ether group to the electrophilic silene silicon atom does not provide a comparable stabilization to the SiC system and the respective derivatives generated were converted into resultant products.     

A new approach to helical primary structures of four-membered rings: (P)- and (M)-tetraspiro[3.0.0.0.3.2.2.2]hexadecane

A new approach to helical primary structures of four-membered rings uses a cycloaddition of a trimethylenketeniminium salt to suitable tailored methylenecyclobutanes to assemble the desired carbon framework. The results are short and effective syntheses of (M)-trispiro[3.0.0.3.2.2]tridecane [(M)-5], and (P)- and (M)-tetraspiro[3.0.0.0.3.2.2.2]hexadecane [(P)- and (M)-24]. Unlike helices of three-membered rings, the specific rotation decreases, as the length of the helix increases.     

Synthesis and Crystal Structure of 2-(Diphenylphosphine oxide)-3-(diphenylphosphine oxide ethynyl) spiro [bicyclo[2.2.1]hepta-2,5-diene-7,1''''-cyclopropane]

1 INTRODUCTION Organic phosphine compounds always attract great interest for their unique properties and extensive uses in biochemistry, pesticide chemistry and synthetic organic chemistry. In the last two decades, much attention has been paid to phosphorus-containing olefin and acetylenic compounds for their applications in transition metal chemistry, asymmetric catalysis and photorearrang- ement [1~7 ]. Previously, we have reported the crystal structure of a novel host compound which …     

Synthesis and x-ray diffraction analysis of 1-methyl-5-(methoxycarbonylmethyl)-4,6-dioxa-1-azoniabicyclo[3.3.0]octane bromide

The reaction of methyl bromopropiolate with diethanolmethylamine gave a quaternized 5-(methoxycarbonylmethyl)-4,6-dioxa-1-azabicyclo[3.3.0]octane, the structure and conformation of which were studied by x-ray diffraction analysis.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1695–1697, December, 1991.     

1,5-二甲基-2-(S)-(1''''-苯基乙基)-2-氮杂-8-氧杂-双环[3.3.0] 辛烷-3,7-二酮的合成及其结构表征

利用2,3-丁二酮与丙二腈缩合形成双甲基双氰基环并内酰胺,经酸性水解得到双甲基环并内酯,然后和(S)-(-)-(1-苯基乙基)胺反应生成1,5-二甲基-2-(S)-(1′-苯基乙基)-2-氮杂-8-氧杂-双环[3.3.0]辛烷-3,7-二酮,通过元素分析、红外光谱、核磁共振氢谱和质谱对其结构进行了表征.用X射线单晶衍射法测定了目标产物的晶体结构,结果表明,晶体属单斜晶系,P21空间群,a=0.8777(18)nm,b=1.0102(2)nm,c=0.9009(18)nm,β=118.75(3)°,V=0.7003(2)nm3,Dc=1.296 g·cm-3,μ=0.089 mm-1,F(000)=292,Z=2,R1=0.0393,wR2=0.0955.     

Synthesis of [1′-(diphenylthiophosphoryl)ferrocenyl]ethyne and alkyne-metal complexes thereof

The novel functionalized ferrocene alkyne Ph₂P(S)fcCCH (1; fc = ferrocene-1,1′-diyl) was synthesized from Ph₂P(S)fcCHO (6) via the Corey-Fuchs reaction. It was further reacted with K₂[HgI₄]/KOH to give mercury(II) acetylide Hg{CCfcP(S)Ph₂}₂ (8), and with [Co₂(CO)₈] to afford the trimetallic Co₂Fe complex [(μ-η²:η²-1){Co(CO)₃}₂](Co-Co) (9). All compounds were characterized by spectral methods (IR, NMR, and MS) and by combustion or high-resolution MS elemental analyses. In addition, the crystal structures of 1, Ph₂PfcBr (5), 6, Ph₂P(S)fcCHCBr₂ (7), and 9 were determined by single-crystal X-ray diffraction.