Studies on the stereoselective selenolactonization, hydroxy and methoxy selenenylation of α- and β-hydroxy acids and esters. Synthesis of δ- and γ-lactones

The diastereoselective synthesis of hydroxy substituted γ- and δ-lactones was accomplished following two approaches. A 5- or 6-endo cyclization promoted by electrophilic selenium reagents of α- or β-hydroxy acids and a 5- or 6-exo cyclization of hydroxy esters obtained through a diastereoselective hydroxy selenenylation reaction of α- or β-hydroxy esters. Moreover, the diastereoselective methoxy selenenylation of the above compounds was investigated showing a case in which the compound that was unreactive in the hydroxy selenenylation conditions gave, in the methoxy selenenylation conditions, the deprotected diol. The usefulness of the methoxy selenenylation procedure was proven by the preparation of a symmetric compound unsymmetrically functionalized. Yields and selectivities were found to depend on substituents (Ph or alkyl groups at the carbon atom that undergoes the nucleophilic attack), mode of cyclization, kinetic or thermodynamic control conditions. In the latter case, silica gel played an important role.     

Regioselective lithiation of aryl benzyl ethers

The lithiation of a series of aryl benzyl ethers containing -F and -OMe groups has been studied. It was found that the presence of one or two fluorine atoms in the meta position relative to the oxygen atom prevents the lithiation at the benzyl carbon atom. 3-(3′,5′-Dimethoxybenzyloxy)fluorobenzene was lithiated and next reacted with DMF to give 2-(3′,5′-dimethoxybenzyloxy)-6-fluorobenzaldehyde. A three-step procedure was applied to remove three hydrogen atoms from 1,3-difluoro-5-(3′,5′-dimethoxybenzyloxy)benzene and replace them with methyl groups by reactions of the lithiated compounds with MeI.     

A novel cyclization reaction of o-carboxyphenyl and o-carbamoylphenyl sulfoxides : Formation of benzoxathiane,dihydrobenzothiazine and benzoisothiazoline derivatives

When o-carboxyphenyl or o-carbamoylphenyl sulfoxide was heated with a large excess of acetic anhydride at 100–130° for 1–3 h, 6-membered heterocyclic compounds, i.e., 3,1 - benzoxathian-4 - one and 2,3 - dihydro - 1,3 - benzothiazin - 4 - one, and a 5-membered heterocyclic compound, i.e., 1,2-benzoisothiazolin-3-one were obtained in good yield.Cyclization would take place by the initial intramolecular nucleophilic attack of either the sulfinyl O atom at ortho-carbonyl carbon or the N atom of the amide group at ortho-sulfinyl S atom to give a 5-membered cyclic acyloxysulfonium salt or aminosulfonium salt, which undergoes an intramolecular Pummerer rearrangement to afford the heterocyclic compounds.     

Determination of microgram amounts of carbon in the for of carbamate by non-aqueous electrolytic conductivity detection

An absorption/detection system is described for the determination of carbon at and below microgram detection level. The carbon dioxide formed by combustion of an organic substances (solid or in solution) is led into a simple absorption/detection system containing 2.00 cm³ of an ethanolic 2 M solution of 3-methoxypropylamine. The conductivity of the carbamate solution formed is measured by means of platinum electrodes built in the absorption tube, and the integrated d.c. voltage signal obtained is fed to a precision digital voltmeter. Detector response is linear up to 6.6 μg of carbon, and the detection limit is 2 × 10^?2 μg. A single determination takes 5 min. Precision was found to be better than +? 1.0% (P-=95%) for 1–6 μg or carbon.     

(η6-1,2,3-Trimethoxybenzene) tricarbonylchromium complex: regioselectivity of the deprotonation

Deprotonation of (h⁶-1,2,3-trimethoxybenzene)tricarbonyl chromium with n-BuLi occurs mainly at the C4 carbon while the use of LiTMP gives predominantly the C5-substituted product.     

Theoretical study of the imidazolidinone catalyzed 1,4-addition of N,N-dimethyl-3-anisidine with α,β-unsaturated butyric aldehyde

Friedel–Crasfts alkylation reactions of α,β-unsaturated butyric aldehydes with N,N-dimethyl-3-anisidine catalyzed by a (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidin-4-one HCl salt have been carried out at the PCM(CH₂Cl₂)/B3LYP/6-311++G(d,p)//B3LYP/6-31G(d) level. Three reaction processes have been characterized: (I) the formation of an iminium ion intermediate; (II) the 1,4-iminium addition of the iminium ion; and (III) the hydrolysis of the addition product. Moreover, Path 1-1 is the favorable channel in the formation of the iminium ion. From the point of view of energy, the enantioselectivity is controlled by the carbon–carbon bond formation step that is involved in both the intermediate M4 and the transition state TS4. The highest energy barrier of the reaction is the H2 proton transfer from the O10 atom of a water molecule to the N1 atom of the catalyst in the hydrolysis process, which is 23.4 kcal/mol. The presented calculated results may be helpful in understanding the experimental product distribution for the title reaction, and provide a general model to help explain the mechanisms of similar reactions.     

Asymmetric synthesis of (?)-(R)-massoia lactone, (R)-δ-decalactone, and (+)-(3R,5R)-3-hydroxydecano-5-lactone. Formal synthesis of verbalactone

A simple and efficient procedure for the asymmetric synthesis of (?)-(R)-massoia lactone, (R)-??-decalactone, and (+)-(3R,5R)-3-hydroxy-1,5-decanolide is described. Verbalactone was synthesized using Heck allylation at the key stage of construction of the carbon skeleton.     

Regioselective ring opening of unsymmetrical cyclic ethers with the A1C13-NaI-acetonitrile system: Application to hydroxylation of ent-kaurene.

Unsymmetrically substituted 5-membered cyclic ethers were effectively cleaved with the A1C1₃-NaI-CH₃CN system at the less hindered carbon atom to afford δ-iodoalcohols. Conversion of ent-kaurene to ent-14α- and ent-12β-hydroxykaurene was achieved through the ring opening of the cyclic ether with the present system as a key step.     

Synthesis of oxoindolin-3-ylidene-1,3-dithioles

An efficient and one-pot synthesis of 2-(2-oxoindolin-3-ylidene)-1,3-dithiole-4,5-dicarboxylates by a three-component condensation reaction of isatins, carbon disulfide and dialkyl acetylendicarboxylates in the presence of Bu₃P is reported. Reaction of carbon disulfide and dialkyl acetylene dicarboxylates with acenaphthylene-1,2-dione, ninhydrine and pyrimidine-tetraone resulted in the formation of 2-(2-oxoacenaphthylen-1(2H)-ylidene)-1,3-dithiole-4,5-dicarboxylates, 2-(1,3-dioxo-1H-inden-2(3H)-ylidene)-1,3-dithiole-4,5-dicarboxylates and 2-(2,4,6-trioxotetrahydropyrimidin-5(6H)-ylidene)-1,3-dithiole-4,5-dicarboxylates, respectively, in the same conditions.     

Reactivity study of 1,1,2,4,4,5,7,7,8,8,9,9,9-tridecafluoro-5-trifluoromethyl-3,6-dioxanon-1-ene in nucleophilic reactions: fluorination properties of secondary amine adducts

A series of nucleophiles was reacted with 1,1,2,4,4,5,7,7,8,8,9,9,9-tridecafluoro-5-trifluoromethyl-3,6-dioxanon-1-ene (1) as a representative of perfluoro(alkyl vinyl ethers). All reactions were completely regioselective with the nucleophilic attack at the terminal carbon atom. Reactions of hydroxy compounds, thiols and sec-amines afforded addition products, but butyllithium, tributylphosphane or complex hydrides caused displacement of vinylic fluorine: butyllithium afforded cis-derivative, while reactions with hydrides and the phosphane led to mixtures of cis- and trans-derivatives. Diethylamine and piperidine adducts displayed the property to substitute hydroxyl for fluorine in hexadecan-1-ol. Molecular properties of hexafluoropropene and perfluoro(methyl vinyl ether) were calculated by ab initio method at the MP2/6-311G(d,p) level of theory and their impact on relative reactivity was estimated.     

Study of the adsorption capacity to Co2+, Ni2+ and Cu2+ ions of an active carbon/functionalized polyamine hybrid material

The retention of Co²⁺, Ni²⁺ and Cu²⁺ metal ions from aqueous solution, on a functionalized hybrid material obtained by the anchorage of N-(4-amino-1,6-dihydro-1-methyl-5-nitroso-6-oxopyrimidin-2-yl)-N′-[bis(2-aminoethyl)] ethylenediamine ligand on a low-functionalized activated carbon, at pH 4.5 has been studied. The adsorption isotherms fit the Langmuir equation and the calculated maximum adsorption capacities were compared to those obtained by using the un-functionalized activated carbon as well as to other analogous hybrid materials as adsorbent of the same metal ions. These studies were carried out by rationalizing the resulting adsorption data regarding the stability constant values of the complexes formed by the three metal ions with the free tri-amine function of the ligand. The results demonstrate that the adsorption capacities of the activated carbon–ligand hybrid material towards the three metal-ions studied correlated with the stabilities of the tri-amine-metal-ion bonds formed during the adsorption processes.     

Highly regioselective heterocyclization reactions of 1H-1,2,4-triazole-3-thiols with chloroacetylenephosphonates

1-Chloroacetylene-2-phosphonates react with 1H-1,2,4-triazole-3-thiols in anhydrous acetonitrile with high regioselectivity to form the fused heterocycles, 6-(dialkoxyphosphoryl)-3H-thiazolo[3,2-b][1,2,4]triazol-7-ylium chlorides 1-5. A significant difference from the previously known reactions of binucleophiles with haloacetylenes is the involvement of both acetylenic carbon atoms in the heterocycle formation. A reaction mechanism is hypothesized that assumes the formation of a sulfenium cation at the acetylene C-1 atom followed by attack of the C-2 atom by the ring N-2 atom. Compounds 1-5 easily lose one alkyl group from the dialkoxyphosphoryl fragment to form zwitterions (e.g., 6-8) which further can be transformed into inner salts 9 and 10 when heated with concentrated hydrochloric acid.     

Enantioselective synthesis of (+)-(S)-7,8-dihydrokavain and (4R,6R)-4-hydroxy-6-(2-phenylethyl)tetrahydro-2H-pyran-2-one, lactone analog of compactin and mevinolin

A simple and efficient asymmetric synthesis was performed of (+)-(S)-7,8-dihydrokanian and (4R,6R)-4-hydroxy-6-(2-phenylethyl)tetrahydro-2H-pyran-2-one involving Keck allylation in the key stage of building up the carbon scaffold of the target molecules.     

Methyl (3R,5R)-3,5-dihydroxydecanoate in the asymmetric synthesis of Idea Leuconoe pheromone and formal syntheses of (+)-(3R,5R)-3-hydroxydecano-5-lactone, verbalactone, and Tolypothrix pentaether

A simple and efficient asymmetric synthesis of (5S,7R)-7-hydroxydodecano-5-lactone, a component of the giant danaine butterfly Idea leuconoe pheromone, and formal syntheses of (+)-(3R,5R)-3-hydroxydecano-5-lactone, verbalactone, and Tolypothrix pentaether have been accomplished starting from methyl (3R,5R)-3,5-dihydroxydecanoate. The latter is obtained from methyl 3-[(tributylstannyl)methyl]but-3-enoate using Keck allylation in the key step of the construction of its carbon skeleton.     

The mechanism of N-haloamide promoted electrophilic additions. high regio and stereoselectivity in the conversion of 2-tert-butyl-3,6-dihydro-2H-pyran into bromohydrins and in the opening of the corresponding epoxides

The reactions of cis- and trans-2-tert-butyl-4,5-epoxytetrahydropyran with HBr and with LAH have been examined as a model for the nucleophilic step of the reaction of the corresponding olefin with NBA in aqueous dioxane. A remarkable 90:10 preference for electrophilic attack syn to the tert -butyl group in the NBA reaction is found and shows that the two epoxides, as well as the intermediate epibromonium ions, undergo nucleophilic attack with high preference for diaxial opening, even when this requires reaction at carbon 5, which is more subject than carbon 4 to the unfavourable inductive effect of the pyran ring oxygen. These results constitute a further proof in favour of a mechanism of N-haloamide promoted electrophilic additions in which the electrophilic step is rapidly reversible and product composition is determined during the nucleophilic step.     

Bromination of 6-dibromomethyl-6-methylcyclohexyl-2,4-dien-1-one

Bromination of 6-dibromomethyl-6-methylcyclohexyl-2,4-dien-1-one (I) with molecular bromine was studied at different ratios of reactants and varied reaction time. A number of tri-, tetra-, penta-, and hexabromo derivatives was obtained, which were characterized by ¹H, ¹³C, IR, UV spectroscopy and elemental analysis. The molecular structure of (2R,3R,4S,5S,6R)-2-dibromomethyl-2-methyl-3,4,5,6-tetrabromocyclohexan-1-one (V) was revealed using XRD. It was shown that 2-bromo-6-dibromomethyl-6-methylcyclohexyl-2,4-dien-1-one (III) upon standing for six months at room temperature dimerized quantitatively via Diels-Alder reaction to form IX. Dimer IX was investigated by the methods of cyclic voltammetry (CVA) and rotating disk electrode (RDE) in a solution of DMF on glassy carbon electrode.     

Synthesis of spirocyclic azacycles from the cyclization of furan tethered N-acyliminium ions

The protic and Lewis acid promoted cyclization reactions of tethered furan-4,5-dihydroxypiperid-2-ones, furan-4,5-diacetoxypiperid-2-ones and furan-3,4-diacetoxypyrrolid-2-ones, via their corresponding N-acyliminium ion intermediates, have been studied. In the case of the furan-4,5-dihydroxypiperid-2-one 2a and its diacetate derivative 2b, macrocyclic products were formed from an initial intermolecular reaction between 2a or 2b, via the nucleophilic C5 furan carbon, and their corresponding N-acyliminium ion intermediates. When the furan C5 position of 2b was blocked by substitution with bromine then TFA or Sc(OTf)₃ catalysed cyclization reactions gave a spirotricyclic product (a 5-6-6-tricycle) in a highly diastereoselective manner. Cyclization of the analogous C5-Br-furan-pyrrolidone 29 with TFA resulted in a related spirotricyclic (a 5-6-5 tricycle) product. Attempts to prepare an analogous azepine system, a 5-7-5 tricycle, were not successful. Cyclization reactions of the C5-PhS-furan- or C5-phenylsulfonyl-pyrrolidone analogues of 29 with TFA were also not successful.     

Oxidative chlorination of 4-pentenols and other functionalized hydrocarbons

Substituted 4-pentenols undergo regio- and stereoselective chlorocyclization, when treated in solutions of dimethyl carbonate with chloride, a terminal oxidant, and a buffered proton source. Effective oxidants for liberating chlorine-like reactivity from chloride in the temperature range between 20 and 40 °C are tert-butyl hydroperoxide, activated by a titanium(IV) or a molybdenum(VI) ONO-chelate complex, and potassium monoperoxysulfate from the ternary salt 2KHSO₅·KHSO₄·K₂SO₄ (oxone^®). Substituents in the flexible part of the alkenol direct oxidative chlorocyclization 2,5-trans- and 2,4-cis-selectively. (E)-Configuration at the alkene translates anti-specifically into relative configuration of substituents at the β-chlorohydrin ether entity. A phenyl group bound to the terminal alkene carbon alters the inherent 5-exo-specificity for chlorocyclization of terminal 4-pentenols toward 6-endo-selectivity, as exemplified by synthesis of trans-3-chloro-2-phenyltetrahydropyran from (E)-5-phenyl-4-penten-1-ol in up to 74% yield. Competition kinetics show that 5-exo-chlorocyclization of 1-phenyl-4-penten-1-ol occurs at 40 °C 600 times faster than electrophilic aromatic chlorosubstitution of anisole. Prenyl-type alkenols undergo allylic chlorination with an ene-type selectivity, as exemplified in synthesis of a building block for the fragrance component rose oxide from citronellol.     

Synthesis of 2,6-disubstituted pyrido[2,3-b][1,4]oxazines

A new preparative method for pyrido[2,3-b][1,4]oxazines from 6-substituted 3-nitro-2-pyridones is demonstrated. This method consists of two steps: O-alkylation and reductive cyclization. In the former step, the bulkiness of both starting nitropyridones and C2 reagents is found to be essential for avoiding N-alkylation, which undergoes O-alkylation efficiently. The subsequent reductive cyclization affords pyridoxazines with carbon substituents at both the 2- and the 6-positions that have not been available.     

Quantum-chemical investigation of reactions of (dialkylamino)ethynylphosphonates with amines

Structural parameters and molecular energies of diethyl piperidylethynylphosphonate, dimethyl (diethylamino)ethynylphosphonate, dimethyl[2-(t-butylamino)-2-(diethylamino)vinyl]phosphonate, N,N-diethyl-N′-t-butyl(dimethoxyphosphinoyl)acetamidine, dimethyl [2-(diethylamino)-2-(phenylamino)vinyl]phosphonate, N,N-diethyl-N′-phenyl(dimethoxyphosphinoyl)acetamidine, and the cations formed by protonation of the phosphinoyl group, nucleophilic carbon atom, or nitrogen were determined by means of B3LYP/6-311G(d₅,p)&;6-31G(d₅,p) quantum-chemical calculations. Acid-base properties of the related amines and their adducts with boron trifluoride in CCl₄ are estimated. The mechanism of the reactions of (dialkylamino)ethynylphosphonates with amines is discussed.