Sonochemical Formation of Iodohydrin and Epoxide from Cyclohexene

Ultrasonic irradiation substantially improves the reaction of cyclohexene with I₂ in aqueous dioxane in the presence of Cu(OAc)₂ · H₂O to generate the expected iodohydrin in high yield. The product undergoes cyclization to the epoxide by biphasic treatment with either Na₂CO₃ or KOH in a sonication‐sensitive step.     

An alternative stereoselective total synthesis of (-)-pyrenophorol

The total synthesis of 16-membered C₂–Symmetric dilactone (-)-Pyrenophorol was accomplished starting from commercially available (S)-epoxide prepared by hydrolytic kinetic resolution of (±) – epoxide with key steps of Grignard reaction, Swern oxidation, Wittig reaction and cyclization was achieved by intermolecular Mitsunobu cyclization. The synthesis of (-)-Pyrenophorol accomplished from cheaply available starting material, easily work-up procedures and reduction of cost in industrial process were major advantages of this route.     

Synthesis and Characterization of Altaicadispirolactone

Altaicadispirolactone was synthesized via a simple route. In this route, levulinic acid was used as a starting material, and bromination followed by hydrolysis and BF₃ · OEt₂‐catalyzed cyclization were carried out. A single‐crystal ORTEP drawing has been created and more detailed crystallographic data of the compound has been obtained from X‐ray analysis.     

Efficient Ce(III)-Catalyzed cis-Selective Synthetic Approach to γ-Lactones in Aqueous Media

The first CeCl₃ · 7H₂O-catalyzed, one-pot synthesis of α-mercapto-γ-lactones via regioselective epoxide ring opening and mercaptoacetylative cyclization cascades in water is reported. The reaction between 2-methyl-2-phenyl-1,3-oxathiolan-5-one and a variety of terminal epoxides was carried out in aqueous media to afford γ-lactones in good to excellent yields (83–94%) with complete cis diastereoselectivity. Acetophenone obtained as a by-product was also recovered and recycled easily for further use.     

Encapsulation of a binuclear manganese(II) complex with an amino acid-based ligand in zeolite Y and its catalytic epoxidation of cyclohexene

A Schiff base ligand was synthesized by the condensation of salicylaldehyde with l-tyrosine. Interaction of this ligand with Mn(II)-exchanged zeolite Y leads to encapsulation of the ligand within the zeolite and complexation of the metal. The encapsulated complex has been characterized by spectroscopic studies and chemical analyses. This material serves as a catalyst for the oxidation of cyclohexene to cyclohexene epoxide and 2-cyclohexene-1-ol using H₂O₂ as oxidant. The reaction conditions have been optimized for solvent, temperature and amount of oxidant and catalyst. The catalyst shows high activity and selectivity toward production of cyclohexene epoxide in acetonitrile at 60 °C with [H₂O₂]/[C₆H₁₀] = 2.5 molar ratio. Comparison of the encapsulated catalyst with the corresponding homogeneous catalyst showed that the heterogeneous catalyst had higher activity and selectivity than the homogeneous catalyst.     

Pathways of cycloaddition of carbodiimides to N-alkenylidenetriflamides: A theoretical study

Possible cyclization pathways for the reaction of (1E,2E)-N-(but-2-en-1-ylidene)triflamide with N,N'-dimethylcarbodiimide have been investigated by DFT and MP2 calculations. The [4+2] route is shown to be thermodynamically unfavorable due to a small content of the reactive s-cis conformer of the azadiene. The [2_CN+2_CN] route has ΔGº>0 and therefore is thermodynamically forbidden. The only allowed route is the [2_CN+2_CC] cycloaddition, which has ΔGº < 0 and leads to 2-methylimino-3-(2-trifliminomethyl)-1,4-dimethylazetidine with further isomerization to 3-(triflamidomethylidene)-2-methylimino-1,4-dimethylazetidine in full agreement with the experimental results. These results indicate the necessity of considering free energy changes rather than only enthalpy changes for accurate prediction of the course of cyclization reactions.     

A variation of the Pictet-Spengler reaction via a sequential reduction-cyclization reaction of N-acylcarbamates: synthesis of 1-substituted tetrahydroisoquinoline derivatives

A new variation of the Pictet-Spengler reaction for the synthesis of 1-substituted tetrahydroisoquinoline derivatives has been developed. The reaction employs the reduction of N-acylcarbamates by DIBAL-H followed by simultaneous cyclization mediated by BF₃·OEt₂. The synthetic potential of this method has been illustrated by the synthesis of the tetrahydroisoquinoline alkaloids, (±)-xylopinine, (±)-laudanosine, (±)-8-oxo-O-methylbharatamine, and (±)-isoindoloisoquinolone.     

A new approach to indolo[2,3-a]quinolizidines through radical cyclization of 2-acyl-1-phenylthiotetrahydro-β-carbolines bearing pendent α,β-unsaturated esters

A new method is reported for the preparation of indolo[2,3-a]quinolizidines based on radical cyclization of a 2-acyl-1-phenylthiotetrahydro-β-carboline bearing a pendent α,β-unsaturated ester. The required radical cyclization precursor is efficiently assembled from E-5-ethoxycarbonyl-4-pentenoic acid and 3,4-dihydro-β-carboline through a DCC/HOBt-activation/N-acylation and BF₃·Et₂O/PhSH iminium-ion trapping sequence. Tin-mediated radical cyclization of the radical cyclization precursor affords stereoselectively a cis-lactam (dr = 7:1) in good yield (81%), bearing the correct D/E ring fusion stereochemistry for the Tacaman alkaloids. The methodology has been applied to formal syntheses of the indoloquinolizidine alkaloids, (±)-eburnaminol and (±)-larutensine.     

Highly Chemoselective Synthesis of Indolizidine Lactams by SmI2‐Induced Umpolung of the Amide Bond via Aminoketyl Radicals: Efficient Entry to Alkaloid Scaffolds

Samarium(II) iodide enables a wide range of highly chemoselective umpolung radical transformations proceeding by electron transfer to carbonyl groups; however, cyclizations of important nitrogen‐containing precursors have proven limited due to their prohibitive redox potential. Herein, we report the first reductive cyclizations of unactivated cyclic imides onto N‐tethered olefins using SmI₂/H₂O. This new umpolung protocol leads to the rapid synthesis of nitrogen‐containing heterocycles that are of particular significance as precursors to pharmaceutical pharmacophores and numerous classes of alkaloids. The reaction conditions tolerate a wide range of functional groups. Excellent chemoselectivity is observed in the cyclization over amide and ester functional groups. Such unconventional reactivity has important implications for the design and optimization of new bond‐forming reactions by umpolung radical processes. The reaction advances the SmI₂ cyclization platform to the challenging unactivated N‐tethered acyl‐type radical precursors to access nitrogen‐containing architectures.     

Synthesis of (±)-heliannuol C

A synthesis of (±)-heliannuol C is described involving Bargellini condensation, Dieckmann cyclization and ortho-ester Claisen rearrangement followed by a regioselective epoxide reduction. A new CuI-catalyzed [2+2] cycloaddition reaction is also described.     

A facile synthesis of simple alkaloids—synthesis of 2,3-polymethylene-4(3H)-quinazolinones and related alkaloids

An efficient procedure for preparation of the simple alkaloids, 2,3-polymethylene-4(3H)-quinazolinones, luotonin A, tryptanthrin, and rutaecarpine has been established by the reaction of lactam-HCl salts with POCl₃ followed by cyclization with methyl anthranilate.     

Research on synthesis and thermodynamic properties of 2-methoxycyclohexanol

2-Methoxycyclohexanol is synthesized through an alcoholysis reaction of cyclohexene oxide and methanol with Ag₂CsPW₁₂O₄₀ as catalyst. The elemental analyzer, FT-IR, GC, and NMR are used to analyze and confirm elements, functional groups, purity, and molecular structure of 2-methoxycyclohexanol. The equation between the specific heat capacity (C _p) and the temperature from 280 to 340 K is fitted by the results of differential scanning calorimeter to examine 2-methoxycyclohexanol. Bomb calorimeter is introduced to determine the standard enthalpy change of combustion of 2-methoxycyclohexanol (? 3938.6 ± 2.0 kJ mol^?1). The standard enthalpy of formation has been calculated as ? 816.88 ± 2.21 kJ mol^?1, based on Hess’s law. These basic thermodynamic parameters are deemed to facilitate the exploitation of new production route of 2-methoxycyclohexanol.     

Diaminobenzene as a Novel Reagent for Nitrite Assay in Environmental Samples: Evidence for Its Mechanistic Aspects

Abstract

o-Phenylenediamine has been used as a reagent to quantify nitrites/nitrates in a variety of sample matrices. The method is based on the cyclization reaction between o-phenylenediamine and nitrite in acid medium. The amine undergoes diazotization with nitrite in the presence of acid to form the diazonium ion, which subsequently cyclizes to yield yellowish orange benzotriazole at room temperature with an absorption maximum at 450 nm. The formed dye has been separated, purified, and characterized by IR, NMR, and spectroscopy techniques. The parameters of the reaction between amine and nitrite have been optimized. The effect of interfering ions on the determination of nitrites/nitrates has been described. The developed method has been applied for the determination of residual NO₂ gas present in the ambient air after fixing it as a nitrite ion using sodium arsenite as a trapping medium. The dye formed has been extracted into organic solvent to improve the detection limit during the measurement of low levels of ambient NO₂ in air. The method obeyed Beer's law in the concentration range 0–250 µg in aqueous medium and 0–50 µg in organic medium with molar absorptivity of 4.09 × 10⁴ L mol^?1 cm^?1 and 4.3 × 10⁴ L mol^?1 cm^?1 respectively. Nitrate is determined by reducing it to nitrite after passing through the copperized cadmium reductor column. The developed method has been applied to determine nitrite/nitrate levels in water, soil, and biological samples.     

An intramolecular para-phenolic allylation free radical cyclization strategy for the synthesis of alkaloids and terpenes with spiro[4.5]decane architectures

A Tsuji-Trost variant of the Winstein-Masamune reaction has been investigated for the synthesis of the AC spirocyclic ring system 9 bearing a quaternary carbon found in the fawcettimine type Lycopodium alkaloids magellanine 1 and lycojaponicumin B 2 and cyclopiane diterpenes such as conidiogenone 3. Annulation of the B ring for the synthesis of tricyclic ABC cores was demonstrated utilizing a 5-exo-trig free radical cyclization of a primary carbon radical onto a cyclohexadienone generated with tri-n-butylgermanium hydride (9 → 11).     

The mechanism of cooxidation of isobutyraldehyde and octene-2

The mechanism of isobutyraldehyde-octene-2 cooxidation at 20°C has been investigated. The ratio of cis to trans epoxides in the reaction products shows that, at aldehyde concentrations lower than 1.0M, the epoxide is formed mainly by a radical route. The difference in the ΔH of formation of cis and trans epoxides is around 0.8 kcal/mole at 20°. The isobutyraldehyde involved in the radical epoxidation chain has been found almost quantitatively to be isopropylhydroperoxide, which is formed through the decarboxylation of i-PrCO₂· radicals, addition of oxygen, and abstraction of hydrogen atoms from the aldehyde. A rate constant of about 14 M^?1 sec^?1 at 20° has been determined for the latter reaction. The chain length for the cooxdination reaction decreases from 75 to 20 as the isobutyraldehyde concentration goes from 1.0 to 0.3M. The termination step seems to involve mainly the interaction of two i-PrO₂ · radicals. The cooxidation of octene-2 with pivalaldehyde follows a similar mechanism, but the chain length is about ten times higher under the same experimental conditions.     

Control of the regiospecific synthesis of dialkylpyrrolizidinones and their stereochemical behaviour using gas chromatography/mass spectrometry with chemical ionization

Pyrrolizidine alkaloids were synthesized via the cyclization of an epoxide prepared from a lactam. The regiospecific control of this reaction is demonstrated using gas chromatography/mass spectrometry. Ammonia chemical ionization mass spectrometry permits the determination of the cis–trans stereochemistry of the final products.     

The cyclization mechanism of <Emphasis Type="Italic">cis</Emphasis> DAA-DAA dipeptide: an ab initio study

The gas-phase cyclization mechanism of cis DAA-DAA dipeptide (where DAA stands for the earlier described double amino acid molecule of (NH₂)₂C(COOH)₂ formula while DAA-DAA indicates the system formed by two DAAs linked via the peptide bond) is investigated in the absence of any catalysts. Two different paths, concerted and stepwise, each leading to the same cyclo(DAA-DAA) dipeptide product are examined on the basis of theoretical calculations carried out at the CCSD(T)/aug-cc-pVDZ//MP2/aug-cc-pVDZ level. The final product of the cyclization was found to adopt boat conformation of the six-membered 2,5-diketopiperazine ring and its formation was predicted to be thermodynamically favored by ca. 3.7 kcal/mol. The activation barrier estimated for the concerted mechanism (39 kcal/mol) was found to be higher than each of two barriers (30–33 kcal/mol) on the stepwise route which indicates that the cyclization process leading to the cyclo(DAA-DAA) dipeptide formation is more plausible when operating along the stepwise pathway.     

Total Synthesis of (−)‐Daphenylline

A concise and highly stereoselective total synthesis of the Daphniphyllum alkaloids (?)‐daphenylline has been accomplished. The synthesis was started from (S)‐carvone and proceeded via a stereoselective Mg(ClO₄)₂‐catalyzed intramolecular amide addition cyclization, an intramolecular Diels–Alder reaction to construct the ABCD tetracyclic core architecture, and a Robinson annulation coupled with an oxidative aromatization sequence. Finally, the DF ring system was installed through an intramolecular Friedel–Crafts cyclization. The total synthesis of (?)‐daphenylline is achieved in 19 steps in the longest reaction sequence and in 7.6 % overall yield.     

Novel synthesis of substituted pyrrolidines and piperidines via radical addition-ionic cyclization reaction of oxime ethers

We have developed a novel synthetic route to nitrogen-containing heterocycles via radical addition-ionic cyclization reaction. Treatment of oxime ethers carrying the tosyloxy group with Et₃B and alkyl iodide in the presence of Lewis acid gave the substituted pyrrolidines and piperidines. The reaction of oxime ethers carrying the methoxycarbonyl group proceeded under the same conditions to give the amino esters, which were easily converted into the corresponding lactams by the treatment with concd HCl. On the other hand, the oxime ether bearing the phenoxycarbonyl group afforded directly alkylated lactams under the radical reaction conditions. The utility of this domino reaction was demonstrated by the synthesis of (±)-bgugaine and the formal synthesis of 5,8-disubstituted indolizidine alkaloids.