Tert-butyl Carbonate Research Articles

Tunable Thermal Degradation of Poly(vinyl butyl carbonate sulfone)s via Side-Chain Branching.

Polymeric materials that depolymerize into volatiles on command may function as vanishing substrates or packaging for transient electronics. Poly(vinyl tert-butyl carbonate sulfone) is known to afford low-boiling byproducts upon heat-activated degradation; however, the polymer is rather unstable, even to the degree of being difficult to process and handle. Understanding the origin of this instability is important for the development of robust materials capable of programmed self-destruction. In this work, we show that poly(vinyl tert-butyl carbonate sulfone)s thermally decompose via carbonate elimination as the rate-determining step, indicating that its thermal instability stems from the lability of the tert-butyl carbonate group. We further examined the effect of isomeric butyl carbonate side chains on the thermal degradation of poly(vinyl butyl carbonate sulfone)s and found that the degradation onsets range from 91 to 213 °C, yielding as little as 2.77 ± 0.53 wt % residue. Results from our findings will aid in the development of vanishing polymers with tunable thermal degradation.

Iron- and Indium-Catalyzed Reactions toward Nitrogen- and Oxygen-Containing Saturated Heterocycles

A myriad of natural and/or biologically active products include nitrogen- and oxygen-containing saturated heterocycles, which are thus considered as attractive scaffolds in the drug discovery process. As a consequence, a wide range of reactions has been developed for the construction of these frameworks, much effort being specially devoted to the formation of substituted tetrahydropyrans and piperidines. Among the existing methods to form these heterocycles, the metal-catalyzed heterocyclization of amino- or hydroxy-allylic alcohol derivatives has emerged as a powerful and stereoselective strategy that is particularly interesting in terms of both atom-economy and ecocompatibility. For a long time, palladium catalysts have widely dominated this area either in Tsuji-Trost reactions [Pd(0)] or in an electrophilic activation process [Pd(II)]. More recently, gold-catalyzed formation of saturated N- and O-heterocycles has received growing attention because it generally exhibits high efficiency and diastereoselectivity. Despite their demonstrated utility, Pd- and Au-complexes suffer from high costs, toxicity, and limited natural abundance, which can be barriers to their widespread use in industrial processes. Thus, the replacement of precious metals with less expensive and more environmentally benign catalysts has become a challenging issue for organic chemists. In 2010, our group took advantage of the ability of the low-toxicity and inexpensive FeCl3 in activating allylic or benzylic alcohols to develop iron-catalyzed N- and O-heterocylizations. We first focused on N-heterocycles, and a variety of 2,6-disubstituted piperidines as well as pyrrolidines were synthesized in a highly diastereoselective fashion in favor of the cis-compounds. The reaction was further extended to the construction of substituted tetrahydropyrans. Besides triggering the formation of heterocycles, the iron salts were shown to induce a thermodynamic epimerization, which is the key to reach the high diastereoselectivities observed in favor of the most stable cis-isomers. It is worth noting that spiroketals could be prepared by using this method, which was successfully applied to a synthetic approach toward natural products belonging to the bistramide family. We then turned our attention to heterocycles incorporating two heteroatoms such as isoxazolidines. These frameworks can be found in biologically active natural products, and in addition, they can be transformed into 1,3-amino alcohols, which are of importance in organic chemistry. The use of FeCl3·6H2O allowed the access to a large variety of 3,5-disubstituted isoxazolidines from δ-hydroxylamino allylic alcohol derivatives with good yields and diastereoselectivities in favor of the cis-isomer. Recently, a Lewis acid-catalyzed synthesis of six- and five-membered ring carbonates starting from linear tert-butyl carbonates was reported. In some cases, the mild and chemoselective InCl3 was preferred over FeCl3·6H2O to avoid side-product formation. The resulting cyclic carbonates were easily transformed into 1,3- or 1,2-diols, and a total synthesis of (3S,5S)-alpinikatin was achieved.

Catalytic wittig reactions of semi- and nonstabilized ylides enabled by ylide tuning.

The first examples of catalytic Wittig reactions with semistabilized and nonstabilized ylides are reported. These reactions were enabled by utilization of a masked base, sodium tert-butyl carbonate, and/or ylide tuning. The acidity of the ylide-forming proton was tuned by varying the electron density at the phosphorus center in the precatalyst, thus facilitating the use of relatively mild bases. Steric modification of the precatalyst structure resulted in significant enhancement of E selectivity up to >95:5, E/Z.

Catalytic Wittig Reactions of Semi- and Nonstabilized Ylides Enabled by Ylide Tuning

The first examples of catalytic Wittig reactions with semistabilized and nonstabilized ylides are reported. These reactions were enabled by utilization of a masked base, sodium tert-butyl carbonate, and/or ylide tuning. The acidity of the ylide-forming proton was tuned by varying the electron density at the phosphorus center in the precatalyst, thus facilitating the use of relatively mild bases. Steric modification of the precatalyst structure resulted in significant enhancement of E selectivity up to >95:5, E/Z.

Gas-phase preparation of carbonic acid and its monomethyl ester.

Carbonic acid (H2CO3), an essential molecule of life (e.g., as bicarbonate buffer), has been well characterized in solution and in the solid state, but for a long time, it has eluded its spectral characterization in the gas phase owing to a lack of convenient preparation methods; microwave spectra were recorded only recently. Here we present a novel and general method for the preparation of H2CO3 and its monomethyl ester (CH3OCO2H) through the gas-phase pyrolysis of di-tert-butyl and tert-butyl methyl carbonate, respectively. H2CO3 and CH3OCO2H were trapped in noble-gas matrices at 8 K, and their infrared spectra match those computed at high levels of theory [focal point analysis beyond CCSD(T)/cc-pVQZ] very well. Whereas the spectra also perfectly agree with those of the vapor phase above the β-polymorph of H2CO3, this is not true for the previously reported α-polymorph. Instead, the vapor phase above α-H2CO3 corresponds to CH3OCO2H, which sheds new light on the research that has been conducted on molecular H2CO3 over the last decades.

Rapid access to spirocyclized indolenines via palladium-catalyzed cascade reactions of tryptamine derivatives and propargyl carbonate.

We report the intermolecular palladium-catalyzed reaction of tert-butyl propargyl carbonate with tryptamine derivatives or other indole-containing bis-nucleophiles. The reaction proceeds under mild conditions and with low catalyst loadings to afford novel spiroindolenine products in good to high yields.

Optimization of a gas chromatography--mass spectrometry method using chemometric techniques for the determination of ezetimibe in human plasma

A new, rapid, and sensitive gas chromatography--mass spectrometry (GC-MS) method was developed for the determination of ezetimibe (EZE) in human plasma. EZE was derivatized prior to GC-MS analysis. Various derivatization techniques such as acetylation, methylation, and silylation were tried. EZE was extracted from plasma with high recovery (94.39%--97.57%) using methyl tertbutyl ether and carbonate buffer (pH 9). Chromatographic conditions were optimized using chemometric methods. In the first step, optimization with factorial design, chromatographic variables (initial and final column temperature, oven ramp rate, and flow rate of gas) were screened to select important variables for the retention of EZE. In the second step, central composite design was applied to decide on the retention time of EZE. The analysis was achieved in a short period of time (

ChemInform Abstract: Highly Enantioselective Synthesis of 3‐Substituted Furanones by Palladium‐Catalyzed Kinetic Resolution of Unsymmetrical Allyl Acetates.

The Pd-catalyzed asymmetric allylic alkylation (AAA) holds a prominent position among the most versatile methods for C C bond formation that are widely applied in natural product synthesis. This transformation typically features broad functional group tolerance and excellent regioand enantioselectivity. In particular, Pd-catalyzed kinetic resolutions of symmetrical allylic substrates and dynamic kinetic transformations have been developed recently, which extends their potential in synthetic chemistry. However, Pd-catalyzed kinetic resolutions of unsymmetrical acyclic allylic substrates with high yield and enantioselectivity are rare. Furthermore, the enantioselective allylic alkylation of silyl enol ethers is still a challenging reaction. Graening and Hartwig reported a highly enantioselective alkylation of monosubstituted allylic substrates with silyl enol ethers catalyzed by an Ir complex. Although excellent results of allylic alkylations have been reported with enolates that are preformed or generated in situ, to the best of our knowledge, Pd-catalyzed AAAwith a nonstabilized silyl enol ether as nucleophile remains an elusive goal (Scheme 1). Herein, we present the Pd-catalyzed kinetic resolution of 1,3-disubstituted unsymmetrical allylic substrates with nonstabilized silyl enol ethers as nucleophiles, which provides a highly regioand enantioselective synthesis of 3-substituted g-butenolides. The g-butyrolactone skeleton is present in more than 13000 natural products, which have attracted considerable attention because of the range of important biological activities associated with this class of compounds. As part of our program to develop catalytic enantioselective methods to access optically active g-butenolides and lactones, we envisioned the possibility of using 2-trimethylsilyloxyfuran (TMSOF) as nucleophile in a Pd-catalyzed AAA reaction. Initially, we examined the allylic substitution of carbonate 1a by utilizing TMSOFas nucleophile and a chiral Pd catalyst based on Trost Ligand L1 (Table 1, entry 1). The 3-substituted product 3 and 5-substituted product 4 were obtained in a 2:1 ratio and in 36% ee for product 3 (Table 1, entry 1). Using a lower temperature (0 8C), the ee value only slightly increased (49% ee, Table 1, entry 2). With tert-butyl carbonate as the leaving group, the regioselectivity shifted in favor of the formation of the 5-substituted product (3/4= 1:2, Table 1,

Highly Enantioselective Synthesis of 3‐Substituted Furanones by Palladium‐Catalyzed Kinetic Resolution of Unsymmetrical Allyl Acetates

The Pd-catalyzed asymmetric allylic alkylation (AAA) holds a prominent position among the most versatile methods for C C bond formation that are widely applied in natural product synthesis. This transformation typically features broad functional group tolerance and excellent regioand enantioselectivity. In particular, Pd-catalyzed kinetic resolutions of symmetrical allylic substrates and dynamic kinetic transformations have been developed recently, which extends their potential in synthetic chemistry. However, Pd-catalyzed kinetic resolutions of unsymmetrical acyclic allylic substrates with high yield and enantioselectivity are rare. Furthermore, the enantioselective allylic alkylation of silyl enol ethers is still a challenging reaction. Graening and Hartwig reported a highly enantioselective alkylation of monosubstituted allylic substrates with silyl enol ethers catalyzed by an Ir complex. Although excellent results of allylic alkylations have been reported with enolates that are preformed or generated in situ, to the best of our knowledge, Pd-catalyzed AAAwith a nonstabilized silyl enol ether as nucleophile remains an elusive goal (Scheme 1). Herein, we present the Pd-catalyzed kinetic resolution of 1,3-disubstituted unsymmetrical allylic substrates with nonstabilized silyl enol ethers as nucleophiles, which provides a highly regioand enantioselective synthesis of 3-substituted g-butenolides. The g-butyrolactone skeleton is present in more than 13000 natural products, which have attracted considerable attention because of the range of important biological activities associated with this class of compounds. As part of our program to develop catalytic enantioselective methods to access optically active g-butenolides and lactones, we envisioned the possibility of using 2-trimethylsilyloxyfuran (TMSOF) as nucleophile in a Pd-catalyzed AAA reaction. Initially, we examined the allylic substitution of carbonate 1a by utilizing TMSOFas nucleophile and a chiral Pd catalyst based on Trost Ligand L1 (Table 1, entry 1). The 3-substituted product 3 and 5-substituted product 4 were obtained in a 2:1 ratio and in 36% ee for product 3 (Table 1, entry 1). Using a lower temperature (0 8C), the ee value only slightly increased (49% ee, Table 1, entry 2). With tert-butyl carbonate as the leaving group, the regioselectivity shifted in favor of the formation of the 5-substituted product (3/4= 1:2, Table 1,

Polycondensation behavior between propargyl carbonates having a bulky ester group and bisphenols in the presence of Pd(0) catalyst: synthesis of exomethylene-containing polyethers

Isopropyl and tert-butyl propargyl carbonates (1b and 1c) were investigated as monomers for Pd(0)-catalyzed polycondensation with bisphenols. These carbonates afforded high-molecular-weight polyethers compared with methyl propargyl carbonate (1a). The number-average molecular weight (Mn) values of the obtained polyethers increased in the order of methyl carbonate 1a<isopropyl carbonate 1b<tert-butyl carbonate 1c. Pd(0)-catalyzed condensation reaction of 1a–c with p-methoxyphenol was carried out as a model reaction. The yield of the desired model product increased with increasing bulkiness of the ester group of 1 (1a<1b<1c). tert-Butyl propargyl carbonate 1c was the most effective for Pd(0)-catalyzed polycondensation with bisphenols. The use of slightly excess 1c yielded higher-molecular-weight polyethers.

A novel practical cleavage of tert-butyl esters and carbonates using fluorinated alcohols

Thermolytic cleavage of t-butyl esters and t-butyl carbonates was accomplished using TFE (2,2,2-trifluoroethanol) or HFIP (hexafluoroisopropanol) as solvent. Thus, a practical method to cleanly convert t-butyl esters and carbonates into the corresponding carboxylic acids, decarboxylated products, or alcohols in nearly quantitative yields was developed. The product is recovered by a simple solvent evaporation. The practicality of this methodology was demonstrated on alkyl, aryl, and heteroaromatic esters.

Gold-catalyzed cyclization of 1-alkynyl cyclopropyl tert-butyl carbonate to construct multifunctionalized vinyl cyclopropane derivatives

A convenient new method was developed to prepare two types of vinyl cyclopropane derivatives through gold-catalyzed cyclization of 1-alkynyl cyclopropyl tert-butyl carbonates 2. Different from the previous reported 5- exo- dig route, the 6- endo- dig addition is the preferred pathway to provide six-membered cyclized carbonates. Two factors, including stereoelectronic effect and steric effect might affect the regioselectivity. Therefore, low steric aliphatic substrates afforded only six-membered isomers. The synthetic utility of compound 3 was also explored to afford a series of β-carbonyl cyclopropanol derivatives.

Thiomaleic Anhydride: A Convenient Building Block for the Synthesis of α-Substituted γ- and δ-Lactones through Free-Radical Addition, Nucleophilic Ring Opening, and Subsequent Thiocarboxylate Manipulation

Iodoalkyl tert-butyl carbonates and carbamates undergo clean free-radical addition to thiomaleic anhydride to give substituted thiosuccinic anhydrides in high yield on treatment with tris(trimethylsilyl)silane and a radical initiator. After removal of the tert-butyloxycarbonyl group, cyclization then affords lactones or lactams substituted in the alpha-position by a thiocarboxylic acid residue. This group is converted to amides through reaction with electron-deficient sulfonamides or to aldehydes and/or ketones by the reaction of derived thioesters with either thiophenol, an electron-deficient allyl phenyl sulfide, or phenylboronic acid.

Phosphine-catalyzed [3+3] annulation reaction of modified tert-butyl allylic carbonates and substituted alkylidenemalononitriles

A phosphine-catalyzed [3+3] annulation reaction of modified tert-butyl allylic carbonates with various alkylidenemalononitriles to form cyclohexenes was developed. The use of protic solvent is crucial in this reaction. When non-polar solvent, toluene or xylene, was used, only non-cyclized product was obtained.

Catalytic Intramolecular Formal [3 + 2] Cycloaddition for the Synthesis of Benzobicyclo[4.3.0] Compounds

In the presence of 20 mol % of tributylphosphine, tert-butyl carbonate substrate 3a undergoes smoothly an intramolecular formal [3 + 2] cycloaddition reaction at room temperature to give benzobicyclo[4.3.0] compounds in 99% yield with a 19/81 ratio of 2a and 2a'. The mechanism of the isomerization of the product 2a into 2a' has been investigated in detail. On the basis of this mechanism, two strategies, using 20 mol % of triphenylphosphine or 10 mol % of tributylphosphine in the presence of 20 mol % of Ti(O(i)Pr)(4), have been established for the selective construction of benzobicyclo[4.3.0] compounds. Under neutral conditions, the reactions of compounds 3a-g afford benzobicyclo[4.3.0] compounds 2a-g with high selectivities in good to excellent yields. In addition, alpha-methyl alpha,beta-unsaturated ester 3h also works well to give the corresponding product 2h with one quaternary carbon center in 99% yield under neutral and room temperature conditions.

Gold-catalyzed rearrangement of propargylic tert-butyl carbonates

Diversely substituted 4-alkylidene-1,3-dioxolan-2-ones are efficiently synthesized by a gold(I)-catalyzed rearrangement of propargylic tert-butyl carbonates. The substrates are readily accessible and the transformation, which is performed under mild reaction conditions using a low loading of catalyst, allows the synthesis of cyclic carbonates, which would be less efficiently obtained using traditional methods. This procedure has also been applied to the stereoselective synthesis of ( E)- or ( Z)-4-halomethylene-1,3-dioxolan-2-ones, which proved to be suitable substrates for palladium-catalyzed cross-coupling reactions.

Organic Carbonates: Experiment and ab Initio Calculations for Prediction of Thermochemical Properties

This work has been undertaken in order to obtain data on thermodynamic properties of organic carbonates and to revise the group-additivity values necessary for predicting their standard enthalpies of formation and enthalpies of vaporization. The standard molar enthalpies of formation of dibenzyl carbonate, tert-butyl phenyl carbonate, and diphenyl carbonate were measured using combustion calorimetry. Molar enthalpies of vaporization of these compounds were obtained from the temperature dependence of the vapor pressure measured by the transpiration method. Molar enthalpy of sublimation of diphenyl carbonate was measured in the same way. Ab initio calculations of molar enthalpies of formation of organic carbonates have been performed using the G3MP2 method, and results are in excellent agreement with the available experiment. Then the group-contribution method has been developed to predict values of the enthalpies of formation and enthalpies of vaporization of organic carbonates.

“Self-Foaming” Poly(phenylquinoxaline)s for the Designing of Macro and Nanoporous Materials

This work concerns the investigation of porous poly(phenylquinoxaline)s (PPQ) films. The approach described relies on the in situ generation of foaming agents during the thermal curing of dense thin films of PPQ-containing thermolabile groups. For this purpose, a series of phenol-containing PPQ has been previously synthesized and then modified by grafting thermolabile tert-butyl carbonate groups (Boc) via a reaction involving the phenol groups. Thin dense films obtained by a solution casting method were thermally treated at different temperatures. The morphology of the resulting porous materials, characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), is discussed in relation with the chemical structure of the polymers and to the thermal treatment conditions as well.

Polymers for nanolithography: A new strategy for design and synthesis of copolymers of maleimide, norbornene, and styrene derivatives with hexafluoroisopropanol and tert-butyl carbonate side groups

Polymers for nanolithography: A new strategy for design and synthesis of copolymers of maleimide, norbornene, and styrene derivatives with hexafluoroisopropanol and tert-butyl carbonate side groups

Tert-Butyl 5-(4-methoxyphenyl)-1-methyl-2-oxopyrrolidin-3-yl carbonate

In the title compound, C17H23NO5, the pyrrolidinone ring is in an envelope conformation. The tert-butyl carbonate and 4-methoxy­phenyl groups are arranged on the same side of the pyrrolidinone ring. The meth­oxy group is coplanar with the attached benzene ring. The mol­ecules are linked into chains along the b axis via C—H⋯O hydrogen bonds.