Stereoselective synthesis of tacalcitol via (R)-MeCBS catalyzed borane reduction

A novel and efficient approach for the synthesis of 1α, 24(R)-dihydroxyvitamin D₃ (tacalcitol) starting from readily available enone 1 has been achieved with high stereoselectivity. The key step involved in the synthesis of tacalcitol was the stereoselective reduction of enone 1 using borane as the reducing agent, and the effects of the critical reaction parameters such as temperature, various borane complexes have been examined. Finally, tacalcitol was obtained in five steps from enone 1 with an overall yield of 32% and a ratio of 24-R/S = 95/5.     

Design and Synthesis of Linearly Fused Triquinanes through Tandem-Metathesis: Access to Basic Core of Cucumin,Capnellene, Chondrosterin,and Xeromphalinone

Herein, a short synthetic approach to linearly fused tricyclic enone 1 and cis-anti-cis type hydroxy-triquinane 2 has been described in an efficient manner by employing tandem-metathesis as a key step. The triquinane-based enone 1 is prepared by a Babler–Dauben oxidation of hydroxy-triquinane 2 , which is assembled by following a three-step sequence involving a regio- and stereoselective allylation, vinyl Grignard addition, and tandem-metathesis. Our strategy relies on exo-tricyclic ketone, which is derived from readily available exo-dicyclopentadiene-1-one. The newly synthesized molecules were identified and characterized by nuclear magnetic resonance spectroscopy (NMR), and high-resolution mass spectrometry (HRMS) data. It is worth mentioning that tricyclic enone 1 is present as a core unit of many naturally occurring polyquinanes, particularly xeromphalinone family members. Hence, our approach may be useful in the synthesis of such bioactive molecules.     

(R)-4-menthenone in reactions of 1,4-conjugate and 1,3-dipolar addition

(R)-4-Menthenone compared with common cyclic enones exhibits considerably lower reactivity in 1,4-conjugate addition of organometallic reagents, is inert in Michael reactions and pyrazoline formation evidently due both to the distorted polarization in the enone system and to steric hindrances from the α-isopropyl group in the cyclohexene ring.     

Gold(I)‐Catalyzed Furan‐yne Cyclizations Involving 1,2‐Rearrangement: Efficient Synthesis of Functionalized 1‐Naphthols and Its Application to the Synthesis of Wailupemycin G

Gold‐catalyzed cascade cyclization/1,2‐rearrangement of 1‐(2‐furanyl)phenyl propargyl alcohols has been developed, which provides a rapid and efficient access to multisubstituted 1‐naphthols bearing an enal or enone moiety with high stereoselectivity. The (Z)‐ or (E)‐stereochemistry can be easily controlled by choosing protected‐ or non‐protected substrates. The utility of the methodology has been illustrated in the first total synthesis of wailupemycin G.     

Conformations of Z- and E-isomers of some chiral (1R,4R)-2-arylidene-p-menthan-3-ones

The ¹Í NMR method in combination with molecular simulation was used to study conformations of Z- and E-isomers of (1R,4R)-cis-2-(4-methoxyphenyl)benzylidene-p-menthan-3-one. In solutions the Z-isomer, unlike the conformationally uniform Å-isomer, is an equilibrium mixture of chair conformers with the substantial predomination of one form with the axially oriented methyl and equatorial isopropyl groups (75—78%). The enone group is more nonplanar in the Z-isomer than in the Å-isomer. For the isopropyl fragment, the equiprobable existence of trans- and two gauche-rotamers for the Z-isomer and a substantial predomination of gauche-forms in the case of the E-isomer were established.     

Four‐Component,One‐Pot Synthesis of 1,4‐Disubstituted 1,2,3‐Triazoles Bearing 1‐(2‐Phenylselenocyclohexyl) Group

An efficient, one‐pot, three‐step, regioselective synthesis of 4‐substituted 1‐(2‐phenylselenocyclohexyl)‐1,2,3‐triazoles, involving in situ generation of l‐azido‐2‐phenylselenocyclohexane has been developed via four‐component reaction of phenylselenenyl bromide, cyclohexene, sodium azide and terminal alkynes catalyzed by copper iodide in a mixture of DMF/THF (1:1) at room temperature under mild conditions with simple workup and good yields.     

Enantioselective Synthesis of Functionalized Nitrocyclopropanes by Organocatalytic Conjugate Addition of Bromonitroalkanes to α,β‐Unsaturated Enones

A general enantioselective synthesis of functionalized nitrocyclopropanes by organocatalytic conjugate addition of a variety of bromonitroalkanes to α,β‐unsaturated enone systems is presented. The process, efficiently catalyzed by the salts of 9‐amino‐9‐deoxyepiquinine 1 d serves as a powerful approach to the preparation of synthetically and biologically important cyclopropanes with high levels of enantio‐ and diastereoselectivities. Since only 0.6 equivalents of bromonitromethane are used as a reagent, (S)‐ 2 e is obtained enantiomerically pure by employing chiral 1 d as a highly efficient catalyst for its kinetic resolution (97 % ee at 51 % conversion, selectivity s=120).     

Light-Induced Cycloaddition of Furan and addition of methanol to a 4-thiacyclohex-2-enone ( = 2,3-dihydro-4H-thiin-4-one) and a 4-thiacyclopent-2-enone ( = thiophen-3(2H)-one)

Irradiation of newly synthesized 2,2-dimethyl-2,3-dihydro-4H-thiin-4-one ( 1 ) in furan affords the two [4 + 2] cycloadducts 3 and 4 and the [2 + 2] cycloadduct 5 in a 5:4:1 ratio (Scheme 1). Irradiation of 1 in MeOH gives a 3:2 mixture of 5- and 6-methoxy-2,2-dimethylthian-4-ones 6 and 7 . Irradiation in CD₃OD affords the same (deuterated) adducts with the CD₃O and D groups trans to each other, results compatible with cis-addition of MeOH to a trans -configurated ground-state enone. Irradiation of the same enone in furan/MeOH 1:1 gives only the furan cycloadducts 3–5 and no MeOH adducts, suggesting that furan interacts with the (excited) triplet enone before the deactivation of this species to a ground-state (E)-cyclohexenone, which then reacts with MeOH. On irradiation in furan, the corresponding five-membered thiaenone, 2,2-dimethylthiophen-3(2H)-one ( 2 ) affords only one, cis-fused, [4 + 2] cycloadduct with ‘exo’-configuration, i.e. 8 , and 2 does not undergo solvent addition but rather cyclodimerization (→ 9 ) on irradiation in MeOH (Scheme 1).     

Competitive Gold‐Promoted Meyer–Schuster and oxy‐Cope Rearrangements of 3‐Acyloxy‐1,5‐enynes: Selective Catalysis for the Synthesis of (+)‐(S)‐γ‐Ionone and (−)‐(2S,6 R)‐cis‐γ‐Irone

We report a simple, highly stereoselective synthesis of (+)‐(S)‐γ‐ionone and (‐)‐(2S,6R)‐cis‐γ‐irone, two characteristic and precious odorants; the latter compound is a constituent of the essential oil obtained from iris rhizomes. Of general interest in this approach are the photoisomerization of an endo trisubstituted cyclohexene double bond to an exo vinyl group and the installation of the enone side chain through a [(NHC)Au^I]‐catalyzed Meyer–Schuster‐like rearrangement. This required a careful investigation of the mechanism of the gold‐catalyzed reaction and a judicious selection of reaction conditions. In fact, it was found that the Meyer–Schuster reaction may compete with the oxy‐Cope rearrangement. Gold‐based catalytic systems can promote either reaction selectively. In the present system, the mononuclear gold complex [Au(IPr)Cl], in combination with the silver salt AgSbF₆ in 100:1 butan‐2‐one/H₂O, proved to efficiently promote the Meyer–Schuster rearrangement of propargylic benzoates, whereas the digold catalyst [{Au(IPr)}₂(μ‐OH)][BF₄] in anhydrous dichloromethane selectively promoted the oxy‐Cope rearrangement of propargylic alcohols.     

Katalytische oxidation von cyclohexen mit IrCl(CO)(PPh3)2 und kritische hydroperoxidkonzentration

Cyclohexene, dissolved in benzene is homogeneously oxidised with IrCl(CO)(PPh₃)₂ as catalyst. No induction period is observed if the concentration of hydroperoxide has a critical value. The reaction rate r increases with the concentration of cyclohexene from r = 1 to 15 mMol O₂ l^?1 min^?1 in pure cyclohexene with turnover numbers of 3000. Product composition is practically independent of the catalyst and cyclohexene concentrations.     

A Green and Novel Method of Synthesizing 2,2'-Arylmethylene Bis(3-hydroxy-5,5-dimethylcyclohex-2-enone) Catalyzed by L-Histidine in Ionic Liquid

An efficient and green approach to the synthesis of 2,2′‐arylmethylene bis(3‐hydroxy‐5,5‐dimethylcyclohex‐2‐enone) using L‐histidine as the catalyst is described. In addition, room temperature ionic liquid 1‐butyl‐3‐methylimidazonium tetrafluoroborate [bmim]BF₄ was used as green recyclable alternatives to volatile organic solvents for this condensation reaction. This green catalytic system can be recycled several times with no decreases in yields and reaction rates.     

A Novel Route to <Emphasis Type="Italic">trans</Emphasis>-Epoxidation of Terpinen-4-ol

Summary. Pure (1S,2R,4S)-1,2-epoxy-p-menthan-4-ol and (1R,2S,4R)-1,2-epoxy-p-menthan-4-ol (trans-epoxides of (4S)-terpinen-4-ol and (4R)-terpinen-4-ol) were prepared and certain reactions of these compounds with nucleophilic reagents were studied. It was shown that the Fürst-Plattner rule regarding the trans-diaxial opening of cyclohexene epoxides predicts the predominant products in all cases studied.     

Structure of (Z)-(5R)-methyl-2-(4-phenylbenzylidene)cyclohexanone as chiral component of liquid-crystalline systems

The spatial structure of (Z)-(5R)-methyl-2-(4-phenylbenzylidene)cyclohexanone prepared by photochemical isomerization of the E-isomer was studied by analyzing the magnitudes and temperature dependence of the proton spin-spin coupling constants obtained by ¹H NMR spectroscopy and the results of molecular modeling using semiempirical quantum chemical AM1 and PM3 methods and the density functional theory (DFT). Comparison of the results obtained for the Z-and E-isomers shows that in both cases the conformational equilibrium for both isomers is characterized by significant preference of the chair conformer having an equatorial methyl group, namely, − ΔH (chair a ⇌ chair e) = 1.98–2.12 and 1.36–1.54 kcal mole⁻¹ for the Z-and E-isomers, respectively. Distinctions in the non-planarity of the enone fragment and cyclohexanone ring in the Z-and E-isomers under study following from the results of mathematical modeling were confirmed by the experimental values of the geminal spin-spin coupling constants of protons of the methylene groups in α,α ′-positions with respect to the enone group. Quantum chemical calculations of the Z-isomer revealed the existence of intramolecular hydrogen bond between the carbonyl oxygen and the nearest aromatic proton in ortho-position of the benzene ring. Possible reasons for different helical twisting power of (Z)-(5R)-methyl-2-(4-phenylbenzylidene)cyclohexanone and the E-and Z-arylidene derivatives of 1R, 4R-isomenthone in the mesophase are discussed based on the results of molecular structure studies for these compounds. In the text below the unsaturated ketones under study will be called “arylidene cyclohexanone derivatives” for convenience of comparing the characteristics of methylcyclohexanone and isomenthone derivatives. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 962–972, June, 2006.     

Nickel Chloride Hexahydrate Catalyzed Multicomponent Biginelli's Synthesis of 3,4‐Dihydropyrimidin‐2(1H)‐Ones and Thiones

An efficient protocol is reported for the one‐pot three‐component Bignelli synthesis of a series of 3,4‐dihydropyrimidine‐2(1H )‐ones and thiones in good yields (66–90%) from the aldehydes (4‐benzyloxybenzaldehyde, 5‐bromovanilin, 4‐formyl‐1‐cyclohexene, and trans‐cinnamaldehyde), β‐keto esters (ethyl acetoacetate, allyl acetoacetate, and t‐butyl acetoacetate), and urea/thiourea in ethanol, using nickel chloride hexahydrate as a catalyst.     

The chemistry of thujone. IX. Thujone as a chiral synthon for the synthesis of optically active steroid analogues. The vinylpicoline route

The thujone-derived enone 1 , upon base-catalyzed reaction with 2-methyl-6-vinylpyridine is converted to the pyridine analogue 5 (Scheme 1). Catalytic reduction of the latter to 6 generates two new centers of chirality which eventually become C(8) and C(14) in the ultimate synthetic steroid analogue 12 . An X-ray analysis of 6 establishes the structure and absolute configuration so as to determine its suitability in subsequent synthetic studies. The acetal derivative 7 , via Birch reduction, hydrolysis, and internal aldol cyclization, is converted into the cyclohexenone analogue 10 (Scheme 2). This ‘one-pot’ process affords an efficient conversion of the pyridine ring into a cyclohexenone system required for A-ring construction of the steroid skeleton. Finally, conversion of 10 , via the unsaturated diketone 11 , provides the chiral steroid analogue 12 .     

Regioselective Deprotection of 1,3-Dibenzyl-5-（N,N-dimethylamino）-6-phenylethyluracil

The deprotection of 1,3-dibenzyl-5-（N,N-dimethylamino）-6-phenyl-ethyluracil I was investigated. A practical, regioselective N3 deprotection of compound I was performed with excellent yield using cyclohexene as a hydrogen donor.     

Reaction of 1,6‐Dioxo‐2,4‐Diene with Aziridine and Secondary Amine

The (2E,4E)‐ and (2E,4Z)‐1‐phenyl‐1,6‐dioxo‐hepta‐2,4‐diene reacts with aziridine to give aziridinecyclopentenol 3. This product arises from an intermolecular Michael addition of a nitrogen lone pair to the less reactive enone, followed by an intramolecular aldol reaction of the enol with ketone. Furthermore, the initially formed enol did not undergo nucleophilic attack onto the aziridine ring to form heterocycles. Interestingly, the reaction with secondary amine did not give the cyclopentenol adduct, and this only leads to the isomerization of (2E,4Z)‐1‐phenyl‐1,6‐dioxo‐hepta‐2,4‐diene to the more stable (2E,4E)‐1‐phenyl‐1,6‐dioxo‐hepta‐2,4‐diene by addition to the more reactive enone.     

Activation and reaction volumes of the reactions of <Emphasis Type="Italic">o</Emphasis>-and <Emphasis Type="Italic">p</Emphasis>-nitrophenylsulfenyl chlorides with styrene and cyclohexene in some solvents

The effect of hydrostatic pressure below 1000 kg cm⁻² on the rate of reactions of o-and p-nitrophenylsulfenyl chlorides with styrene and cyclohexene was studied. The activation and reaction volumes (cm³ mol⁻¹) for the reactions of o-nitrophenylsulfenyl chloride with styrene in acetonitrile (−23.1 and −23.6), 1,2-dichloroethane (−29.2 and −24.7), chlorobenzene (no, −20.2), and anisole (−25.1 and −21.2) and for the reaction of p-nitrophenylsulfenyl chloride with styrene in carbon tetrachloride (−39.5±1.5 and −22.0) were determined. In carbon tetrachloride the activation volumes for the reactions of cyclohexene with o-and p-nitrophenylsulfenyl chlorides (−37.7±2.0 and −40.9±1.2 cm³ mol⁻¹, respectively) are almost the same and coincide with the data for the reactions with styrene. The considerable decrease in the volume of the transition state in the nonpolar solvent is considered as a consequence of the enhanced electrostriction of carbon tetrachloride in the solvate sphere of the transition state of the reaction, which excludes the nonpolar transition state of the sulfuran type. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 477–480, March, 2007.     

Liquid-Phase Cyclohexene Oxidation with O2 over Spray-Flame-Synthesized La1−xSrxCoO3 Perovskite Nanoparticles

La_1−xSr_xCoO₃ (x=0, 0.1, 0.2, 0.3, 0.4) nanoparticles were prepared by spray-flame synthesis and applied in the liquid-phase oxidation of cyclohexene with molecular O₂ as oxidant under mild conditions. The catalysts were systematically characterized by state-of-the-art techniques. With increasing Sr content, the concentration of surface oxygen vacancy defects increases, which is beneficial for cyclohexene oxidation, but the surface concentration of less active Co²⁺ was also increased. However, Co²⁺ cations have a superior activity towards peroxide decomposition, which also plays an important role in cyclohexene oxidation. A Sr doping of 20 at. % was found to be the optimum in terms of activity and product selectivity. The catalyst also showed excellent reusability over three catalytic runs; this can be attributed to its highly stable particle size and morphology. Kinetic investigations revealed first-order reaction kinetics for temperatures between 60 and 100 °C and an apparent activation energy of 68 kJ mol⁻¹ for cyclohexene oxidation. Moreover, the reaction was not affected by the applied O₂ pressure in the range from 10 to 20 bar. In situ attenuated total reflection infrared spectroscopy was used to monitor the conversion of cyclohexene and the formation of reaction products including the key intermediate cyclohex-2-ene-1-hydroperoxide; spin trap electron paramagnetic resonance spectroscopy provided strong evidence for a radical reaction pathway by identifying the cyclohexenyl alkoxyl radical.     

Kinetics of the oxidation of cyclohexene by thallium(III) acetate

The kinetics of the reaction by which thallium(III) acetate oxidizes cyclohexene in glacial acetic acid medium, has been studied by UV spectrophotometric observation at 30°C. The consumption of thallium(III) acetate follows a second-order rate law exhibiting first-order dependence on each of thallium(III) acetate and cyclohexene; however, the first-order dependence on cyclohexene disappears at high cyclohexene concentrations as pseudo-first-order conditions prevail above 0.2 M cyclohexene. A steady-state model of the following form is proposed: where Tl, Cy, and Com are units of Thallium(III) acetate, cyclohexene, and a reaction complex. The value of k₂ has been evaluated as 0.00027 and (k_?1 + k₂) as 0.0385k₁. For low thallium(III) acetate concentrations the reaction kinetics follow the rate law: where α = the excess concentration of cyclohexene over thallium(III) triacetate. For thallium(III) acetate concentrations above 0.02 M, double salt formation of thallium(III) acetate with product thallium(I) acetate removes thallium(III) acetate from the reaction and a modified rate law is observed. Runge–Kutta numerical solutions to the differential equations provide confirmation that the rate expressions are valid in predicting the observed concentrations of thallium(III) acetate.