Intramolecularly two-centered cooperation catalysis for the synthesis of cyclic carbonates from CO2 and epoxides

A catalyst system containing an electrophilic center and a sterically hindered nucleophilic center in one molecule was applied to the cycloaddition reaction of CO₂ and epoxides. This intramolecularly two-centered cooperation catalyst showed activity even at a high [epoxide]/[catalyst] ratio up to 50 000 under mild conditions such as solvent-free, ambient temperature, and low CO₂ pressure. The reaction of CO₂ with (S)-propylene oxide at 80 °C in the presence of the bifunctional catalyst gives (S)-propylene carbonate in 96% ee with retention of stereochemistry.     

Location of type B carbonate ion in type A-B carbonate apatite synthesized at high pressure

The structure of a complex, disordered type A-B carbonate apatite (CAp) of approximate composition Ca₁₀(PO₄)_6−y(CO₃)_x+(3/2)y(OH)_2−2x, x-0.7, y-0.6, synthesized at 3 GPa, 1400°C has been determined using single-crystal X-ray diffraction and FTIR spectroscopy at room temperature and pressure. Crystal data are: hexagonal, space group P6₃/m, Z=1; a=9.5143(3), c=6.8821(2) Å, V=539.5 Å³, and R=0.025. There are three structural locations for the carbonate ion. The channel carbonate is mainly in the closed vertical configuration of the structure, with two of its oxygen atoms close to the c-axis (A1 carbonate; IR bands at 1541 and 1449 cm⁻¹), but subordinate amounts are also located in an open vertical configuration (A2 carbonate; IR bands at 1563 and 1506 cm⁻¹). The type B carbonate ion is located close to the sloping faces of the PO₄ tetrahedron (IR bands at 1474 and 1406 cm⁻¹), confirming earlier inferences from polarized IR spectra.     

Inverse stereoselectivity in the nucleophilic attack on five-membered ring oxocarbenium ions. Application to the total synthesis of 7-epi-(+)-goniofufurone

A highly stereoselective nucleophilic substitution at the anomeric position of 1,2-O-isopropylidene furanose derivatives was employed for the synthesis of 7-epi-(+)-goniofufurone and two of its stereoisomers. According to Woerpel's model, the stereoselectivity depends essentially on stereoelectronic factors that lead to a preferred nucleophilic attack on the inside face of the five-membered ring oxocarbenium ion in a folded conformation, whereby the stereochemical outcome generally is controlled by the substituent at the C3 position (OR group). Herein, we developed a strategy for a reverse stereoselective nucleophilic substitution, by placing an acetyl group at the C5 position of the xylofuranose ring, leading now to the nucleophilic approach on the outside face of the respective oxocarbenium ion. With this methodology, starting from diacetone-d-glucose derivative, we were able to achieve in seven steps the total synthesis of the powerful anti-tumor compound 7-epi-(+)-goniofufurone in a remarkable overall yield of 33%.     

Cesium carbonate as a mediated inorganic base in some organic transformations

Cesium carbonate is a type of alkali carbonate salt having a remarkable number of applications and has been demonstrated to be a mild inorganic base in organic synthesis. It has received much attention for its utility in C, N, O alkylation and arylation reactions. Cesium carbonate not only promotes successful carbonylation of alcohols and carbamination of amines, but also suppresses common side reactions traditionally encountered with other protocols. It is used also in six-membered annulation, intramolecular and intermolecular cyclizations, Suzuki coupling, aza-Henry, nucleophilic substitution, cross coupling and different cycloaddition reactions.     

Ozonolysis of bis-endo-diacylbicyclo[2.2.1]heptenes in dichloromethane-methanol

Ozonolysis of bis-endo-diacylbicyclo[2.2.1]heptenes 3a-d at −78 °C in dichloromethane-methanol gave the hydroperoxides 6a-d in 70-80% yields. Ozonolysis of bis-endo-diacetylbicyclo[2.2.2]octene 15 and bis-endo-diacetyl-7-oxabicyclo-[2.2.1]heptene 16 under the same reaction conditions gave the hydroperoxides 17 and 18, respectively. The intramolecular sequential nucleophilic addition of the carbonyl groups to the carbonyl oxide group was observed for the first time and was found to be faster than the intermolecular nucleophilic addition of a methanol molecule to the carbonyl oxide group. Ozonolysis of compound 23 in CH₂Cl₂-MeOH at −78 °C followed by reduction with Me₂S gave compounds 24 and 25, in which the stereochemistry of the methoxyl groups was determined by X-ray analysis.     

Neighboring effect of the lactam functionality in select reactions of 6-azaspiro[4.5]decane-1,7-dione

The susceptibility of 6-azaspiro[4.5]decane-1,7-dione (4) to nucleophilic attack was evaluated. Although steric effects preclude the 1,2-addition of many reagents, more reactive lithium and Grignard species react. Attack from the direction syn to the lactam functionality predominates. The acid-catalyzed rearrangement of select products delivered allylic alcohols carrying their double bond at varying distances from the spirocyclic carbon. These designed systems undergo hydrogenation predominantly from that π-surface syn to the amide component, the more so when a hydroxyl is proximate to these hetero atoms. The same phenomenon operates when N-benzoylated intermediates are hydrolyzed with potassium carbonate in methanol.     

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.     

Nitropyrazoles 23. Synthesis of substituted N-amino-3-nitro-5-R-pyrazoles

The study is devoted to nucleophilic substitution of nitro groups in 1-amino-3,5-dinitropyrazole (1) and its amino group derived analogs. Compound 1 upon treatment with S-nucleophiles undergoes regioselective substitution of the nitro group at position 5. Azomethine 5 obtained by the condensation of 1 with benzaldehyde gives the nucleophilic substitution reaction with S-, O-and N-nucleophiles also with involvement of the nitro group at position 5. The synthesized 5-R-substituted azomethines 7–9 upon treatment with hydrazine hydrate form N-amino-5-R-3-nitropyrazoles and benzaldazine.     

Nitropyrazoles 22. On reactivity of 3,5-dinitro-4-(phenylsulfonyl)pyrazole and its N-methyl derivative

3,5-Dinitro-4-(phenylsulfonyl)pyrazole (5) obtained by oxidation of 3,5-dinitro-4-(phenylthio)pyrazole with 30% H₂O₂ in AcOH was involved into nucleophilic substitution reaction with thiophenol, which proceeded with substitution of the phenylsulfonyl group at position 4. N-Methyl-3,5-dinitro-4-(phenylsulfonyl)pyrazole obtained by methylation of 5 with dimethyl sulfate was involved into nucleophilic substitution reaction with thiophenol, p-bromophenol, and morpholine with the regioselective substitution of the nitro group at position 5 to form 5-R-3-nitro-4-(phenylsulfonyl)pyrazoles.     

Diethoxyphosphorylmethylfurans in Curtius reaction

Methyl (diethoxyphosphorylmethyl)furoates are selectively hydrolyzed at the carboxy group with the equimolar amount of potassium hydroxide in ethanol. The carboxylic acids obtained by means of the consecutive treatment with ethyl chloroformate in the presence of triethylamine and sodium azide are converted into furoyl azides. 3-Furoylazides and 5-(diethoxyphosphorylmethyl)-2-furoyl azide while heating to 110°C undergo Curtius rearrangement in the corresponding isocyanates which add methanol to form stable methyl urethanes. 4-(Diethoxyphosphorylmethyl)-5-methyl-2-furoyl azide also forms stable isocyanate, but while treating this substance with methanol the process does not stop on the formation of methyl urethane. Addition of the second methanol molecule takes place, and the subsequent nucleophilic substitution and elimination of ammonia lead to O-[4-(diethoxyphosphorylmethyl)furyl-2](methyl)carbonate. 3-(Diethoxyphosphorylmethyl)-2-furoyl azide forms polymer at 100°C in toluene, but while boiling it in the 1:1 toluene-methanol mixture formation of urethane is observed spectroscopically. The latter compound also undergoes conversion to phosphorylated furyl carbonate. By means of the ¹H and ³¹P NMR spectroscopy the intermediate products formed in the course of transformations described were traced, and on this basis probable mechanisms of addition of methanol to isocyanate and rearrangement of urethane to carbonate were suggested.     

Nucleophilic additions of lithiated allylphenylsulfone to nitrones: experimental and theoretical investigations

The nucleophilic addition of lithiated allylphenylsulfone to nitrones at −80 °C proceeds exclusively α to the phenylsulfonyl group affording anti adducts in high yield. At 0 °C isoxazolidines are obtained with complete all-trans selectivity. The formation of these compounds involves isomerization of the allylsulphonyl moiety to give a transient vinylsulfone that then undergoes a subsequent intramolecular Michael addition. The addition to several nitrones has been studied and theoretical calculations have been refined to accurately explain the selectivity of the allylation reaction.     

Sterically Facilitated Intramolecular Nucleophilic NMe2 Group Substitution in the Synthesis of Fused Isoxazoles: Theoretical Study

The influence of steric repulsion between the NMe₂ group and a second ortho-(peri-)substituent in the series of 1-dimethylaminonaphthalene and N,N-dimethylanilene ortho-oximes on the ease of the NMe₂ group’s intramolecular nucleophilic substitution is studied. Possible reaction intermediates for three mechanisms are calculated (ωB97xd/def-2-TZVP), and their free Gibbs energies are compared to model reaction profiles. Supporting experiments have proved the absence of studied reactivity in the case of simple 2-dimethylaminobenzaldoxime, which allowed us to establish reactivity limits. The significant facilitation of NMe₂ group displacement in the presence of bulky substituents is demonstrated. The possibility of fused isoxazoles synthesis via the intramolecular nucleophilic substitution of a protonated NMe₂ group in the aniline and naphthalene series is predicted.     

Alkaloids-catalyzed regio- and enantioselective allylic nucleophilic substitution of tert-butyl carbonate of the Morita-Baylis-Hillman products

The alkaloids-catalyzed regio- and enantioselective allylic nucleophilic substitution reactions of tert-butyl carbonate of the Morita-Baylis-Hillman products with pronucleophiles are reported. A number of pronucleophiles, such as nitrogen, oxygen, and active carbon pronucleophiles have been used in this facile reaction. In general, the reaction proceeded efficiently to give the substitution product in good yields with high regioselectivity and medium enantioselectivity.     

A Zinc-Mediated Deprotective Annulation Approach to New Polycyclic Heterocycles

A straightforward approach to new polycyclic heterocycles, 1H-benzo[4,5]imidazo[1,2-c][1,3]oxazin-1-ones, is presented. It is based on the ZnCl₂-promoted deprotective 6-endo-dig heterocyclization of N-Boc-2-alkynylbenzimidazoles under mild conditions (CH₂Cl₂, 40 °C for 3 h). The zinc center plays a dual role, as it promotes Boc deprotection (with formation of the tert-butyl carbocation, which can be trapped by substrates bearing a nucleophilic group) and activates the triple bond toward intramolecular nucleophilic attack by the carbamate group. The structure of representative products has been confirmed by X-ray diffraction analysis.     

A mild and practical method for the regioselective synthesis of N-acylated 3,4-dihydropyrimidin-2-ones. New acyl transfer reagents

The treatment of 3,4-dihydropyrimidin-2-ones with n-BuLi at −78 °C, followed by quenching with various electrophiles furnished N3-substituted derivatives, regioselectively. Further, N1,N3-diacyl derivatives were found to transfer N1-acyl groups to nucleophilic sites.     

Regioselective reaction of 5,6-dialkyl-2-halopyridine-3,4-dicarbonitriles with ammonia

The reaction of 5,6-dialkyl-2-halopyridine-3,4-dicarbonitriles with alcoholic ammonia under elevated pressure gave 5,6-dialkyl-2-aminopyridine-3,4-dicarbonitriles as a result of nucleophilic replacement of the halogen atom by amino group. 6,7-Dialkyl-4-halo-1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diimines were formed in analogous reaction at room temperature in the presence of potassium carbonate.     

Regio- and stereoselectivity of the 3-membered ring opening of some 3,4-epoxytetrahydropyrans and of the corresponding epibromonium ions

The reactions of 3,4-epoxytetrahydropyran and of its cis- and trans-2-methyl derivatives with hydrogen halides and with lithium aluminum hydride have been investigated in order to assess the influence of an O atom in the β position on the regioselectivity of the epoxide ring opening. All these reactions exhibit a high preference for nucleophilic attack at position 4, which decreases moderately only when the inductive effect of the O atom and the stereoelectronic requirements of the attack act in opposite directions. Similar trends are observed in the reactions of the 5,6-dihydro-2H-pyrans with NBA, which occur with preferential nucleophilic attack by water at position 4 of the intermediate epibromonium ions. A remarkably high preference (96%) for electrophilic attack syn to the 2-Me group is observed in the latter type of reaction, in accordance with a previous proposal of a mechanism in which the nucleophilic step is rate determining.     

Peroxysolvates of carbamide and sodium carbonate in the nucleophilic decomposition of paraoxon

The nucleophilic decomposition of paraoxon (4-nitrophenyl ester of diethylphosphoric acid) by the HOO⁻ anion generated from peroxysolvates of sodium carbamide and carbonate in aqueous, micellar, microemulsion, and water–ethanol media was studied. Feasibility was demonstrated for the use of solid sources of hydrogen peroxide in decontaminating nucleophilic systems.     

Direct conversion of 1-deoxy-1-nitroalditols to methyl glycofuranosides

Treatment of the sodium nitronate forms of 1-deoxy-1-nitrohexitols with methanolic sulfuric or hydrochloric acid at −30 °C leads to their regiospecific conversion to the corresponding methyl glycofuranosides. The reaction exhibits more pronounced stereoselectivity for 1-deoxy-1-nitroalditols with the 2,3-erythro configuration than with the 2,3-threo substrates and cis methyl glycofuranosides are the major products. The observed stereoselectivity indicates the lysis of the protonated aci-nitro form which is a two-step process consisting of nucleophilic addition to the protonated carbon-nitrogen double bond followed by the bimolecular nucleophilic substitution of the nitrogen-containing residue.     

Type A-B carbonate chlorapatite synthesized at high pressure

Sodium-bearing type A-B carbonate chlorapatites {CCLAP; Ca_10−(y+z)Na_y□_z[(PO₄)_6−(y+2z)(CO₃)_y+2z][Cl_2−2x(CO₃)_x], with x≈y≈4z≈0.4} have been synthesized from carbonate-rich melts at 1350-1000 °C and 1.0 GPa, and investigated by single-crystal X-ray structure and FTIR spectroscopy. Typical crystal and compositional data are: a=9.5321(4) Å, c=6.8448(3) Å, space group P6₃/m, R=0.027, R_w=0.025, x=0.37(3), y=0.57(2). Crystal-chemical features and FTIR spectra are similar to Na-bearing type A-B carbonate hydroxyapatites (CHAP) and fluorapatites (CFAP) reported recently. The molar amounts of Na and channel (type A) carbonate maintain a near 1:1 ratio in all three composition series, confirming that the Na cation and A and B carbonate ion substituents exist as a defect cluster within the apatite matrix, to facilitate charge compensation and spatial accommodation. Uptake of carbonate is significantly lower in CCLAP than in CHAP for similar conditions of crystal synthesis.