Rearrangement Of Esters Research Articles

Synthesis of Cyclic β-Amino Acid Derivatives by Desymmetrization and Lossen Rearrangement of N-Sulfoxy Meso-Succinimides.

Bifunctional thiourea-based organocatalysts facilitate an enantioselective desymmetrization and Lossen rearrangement cascade reaction of N-sulfoxy meso-succinimides, resulting in the synthesis of cyclic β-amino acid derivatives. This catalytic system was optimized for bicyclic and tricyclic succinimide substrates affording yields from 61-91% and up to 96:4 er. This reaction proceeds via the group selective addition of the primary alcohol nucleophile to an enantiotopic carbonyl group with sequential rearrangement of the intermediate O-sulfonyl hydroxamate ester.

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters.

An efficient multicomponent reaction of newly designed β-trifluoromethyl β-diazo esters, acetonitrile, and carboxylic acids via an interrupted esterification process under copper-catalyzed conditions has been developed, which affords various unsymmetrical β-trifluoromethyl N,N-diacyl-β-amino esters in good to excellent yields. The reaction features mild conditions, a wide scope of β-amino esters and carboxylic acids, and also applicability to large-scale synthesis, thus providing an efficient way for the synthesis of β-trifluoromethyl β-diacylamino esters. Furthermore, this reaction represents the first example of a Mumm rearrangement of β-trifluoromethyl β-diazo esters.

Visible-light-mediated substituent-controlled regiodivergent (2 + 2)/(3 + 2) cycloadditions for the synthesis of aza-analogs of β-lactam and γ-fused lactam derivatives

Substituent-controlled regiodivergent synthesis of aza-analogs of β-lactam and γ-fused lactam derivatives via the visible-light-induced Wolff rearrangement of α-diazoketones and azo esters.

Preparation and Carbocupration–Silylation of Allyl Propiolates: Vicinal Functionalization To Form Polysubstituted (E)-Vinylic Silanes

AbstractThe preparation and TMSOTf-mediated catalytic carbocupration–silylation of allylic propiolates has been investigated, expanding on previous syntheses of a variety of β-alkyl- and β-aryl-substituted vinylsilanes from an ethyl propiolate precursor. With few exceptions, the series of synthesized O-allyl (E)-vinylsilanes has been isolated in high yields (61–89%) with exceptional diastereoselectivities (E/Z >20:1). Additionally, we demonstrated a novel LDA-initiated, TMSCl-mediated Ireland–Claisen rearrangement of a representative allylic ester.

Umpolung Reactivity of Diazo Arylidene Succinimides: Distal C-H Functionalization of α-Thiocarbonyls from the Reactive Carbenoid Center.

Herein, for the first time we have explored the umpolung reactivity of vinylogous carbon center of diazo arylidene succinimide (DAS) through rhodium catalysis to achieve [2,3]-Stevens rearrangement of α-thioether esters. The protocol has successfully demonstrated the distal C-H bond functionalization of the α-thioether esters. Alongside, the carbenoid reactivity of DAS has also been achieved with Doyle-Kirmse reaction of allyl/propargyl phenyl sulfides. The protocol proved to be practical to synthesize a wide variety of [2,3]-Stevens rearrangement products exclusively and the possible side products emanating from Pummerer rearrangement and [1,2]-Stevens rearrangement were not observed. This catalytic protocol works smoothly in environmentally benign solvent under open air to afford the corresponding desired products with excellent diastereo-, regio- and chemo-selectivities in good to excellent yields. The protocol also proved to be scalable on gram quantity.

Zinc chloride-catalyzed cyclizative 1,2-rearrangement enables facile access to morpholinones bearing aza-quaternary carbons

Morpholines and morpholinones are important building blocks in organic synthesis and pharmacophores in medicinal chemistry, however, C3-disubstituted morpholines/morpholinones are extremely difficult to access. Here we show the ZnCl2-catalyzed cyclizative 1,2-rearrangement for the efficient synthesis of morpholinones bearing aza-quaternary stereocenters. A series of structurally diverse C3-disubstituted morpholin-2-ones which are difficultly accessible by existing methods were efficiently constructed from readily available two achiral linear compounds. Notably, mechanistic studies reveal that this reaction proceeds via an unusual sequence of direct formal [4 + 2] heteroannulation regioselectively delivering specific α-iminium/imine hemiacetals followed by a 1,2-esters or amides shift process, which is different from the reported mechanism of the aza-benzilic ester rearrangements.

Stereoselective Synthesis of α-Fluoro Carboxylic Acids by Ireland-Claisen Rearrangement.

Stereoselective synthesis of α-fluoro carboxylic acids by the Ireland-Claisen rearrangement can provide a straightforward approach to this class of compounds. We report a systematic investigation of base-dependent stereocontrol in the Ireland-Claisen rearrangement of α-fluoro esters. For substrates with various substitution patterns, the use of KN(SiMe3)2 in toluene afforded rearrangement products corresponding to the (Z)-enolate intermediate with a practically useful diastereoselectivity and yield. In contrast, lower yields and diastereoselectivity were consistently observed with the use of lithium diisopropylamide (LDA) in tetrahydrofuran (THF).

The molecular level study of the fate of the CH3CH2C(O)OCH(O)CH3 radical derived from ethyl propionate

ABSTRACT A quantum chemical study has been presented on the decomposition of CH3CH2C(O)OCH(O • )CH3 which is derived from ethyl propionate (CH3CH2C(O)OCH2CH3) using the M06-2X/6-31 + G(d,p) level of theory. The thermal decomposition of CH3CH2C(O)OCH(O • )CH3 is essential to understand the chemistry of combustion of ethyl propionate. Here, the decomposition and oxidative pathways, bond fission and alpha ester rearrangement of CH3CH2C(O)OCH(O • )CH3 have been explored. We have obtained transition states for the different pathways and further verified each transition state by performing intrinsic reaction coordinate (IRC) calculations. The density of state spectra (DOS) was calculated using GaussSum software. The single-point energy calculations are performed at the same function but using larger basis sets such as 6-311++G(d,p) and 6-311++G(3df,2p). We have shown all stationary points and transition states involved in reaction pathways on the potential energy surface (PES) diagram and also discussed the thermochemistry of each reaction pathway. The thermal rate constants of various channels in the decomposition of CH3CH2C(O)OCH(O • )CH3 are determined using the Conventional Transition State Theory (CTST) in the temperature range of 250–450 K and 1atm. From PES, thermochemistry and kinetics analysis, we found that α-ester rearrangement produces propionic acid, which is dominant over the oxidative pathway for the decomposition of CH3CH2C(O)OCH(O • )CH3.

3,3]-Rearrangements of N-Oxyindoles

AbstractThe concerted Ag-catalyzed rearrangement of N-indolyl carbonates and esters to afford 3-oxyindole derivatives with broad functional-group compatibility is presented. In addition, this concerted [3,3]-rearrangement approach was expanded to the synthesis of phosphonate and sulfonamide derivatives without the use of an Ag catalyst. Control experiments suggested that no radical pathway is involved at any stage of the rearrangement process.

Sensitizer-controlled photochemical reactivity via upconversion of red light.

By combining the energy input from two red photons, chemical reactions that would normally require blue or ultraviolet irradiation become accessible. Key advantages of this biphotonic excitation strategy are that red light usually penetrates deeper into complex reaction mixtures and causes less photo-damage than direct illumination in the blue or ultraviolet. Here, we demonstrate that the primary light-absorber of a dual photocatalytic system comprised of a transition metal-based photosensitizer and an organic co-catalyst can completely alter the reaction outcome. Photochemical reductions are achieved with a copper(i) complex in the presence of a sacrificial electron donor, whereas oxidative substrate activation occurs with an osmium(ii) photosensitizer. Based on time-resolved laser spectroscopy, this changeover in photochemical reactivity is due to different underlying biphotonic mechanisms. Following triplet energy transfer from the osmium(ii) photosensitizer to 9,10-dicyanoanthracene (DCA) and subsequent triplet-triplet annihilation upconversion, the fluorescent singlet excited state of DCA triggers oxidative substrate activation, which initiates the cis to trans isomerization of an olefin, a [2 + 2] cycloaddition, an aryl ether to ester rearrangement, and a Newman-Kwart rearrangement. This oxidative substrate activation stands in contrast to the reactivity with a copper(i) photosensitizer, where photoinduced electron transfer generates the DCA radical anion, which upon further excitation triggers reductive dehalogenations and detosylations. Our study provides the proof-of-concept for controlling the outcome of a red-light driven biphotonic reaction by altering the photosensitizer, and this seems relevant in the greater context of tailoring photochemical reactivities.

Host-guest interactions based supramolecular complexes self-assemblies for amplified chemodynamic therapy with H2O2 elevation and GSH consumption properties

Although endogenous H2O2 is overexpressed in tumor tissue, the amount of endogenous H2O2 is still insufficient for chemodynamic therapy (CDT). In addition, the abundant cellular glutathione (GSH) could also consume •OH for reduced CDT. Thus, the elevation of H2O2 and the consumption of GSH in tumor tissue are essential for the increased •OH yield and amplified CDT efficacy. In this paper, host-guest interactions based supramolecular complexes self-assemblies (SCSAs) were fabricated by incorporating cinnamaldehyde (CA) and PEG-modified cyclodextrin host units (mPEG-CD-CA) with ferrocene-(phenylboronic acid pinacol ester) conjugates (Fc-BE) on the basis of CD-induced host-guest interactions. After being internalized by cancer cells, CA can be released from SCSAs through the pH-responsive acetal linkage, elevating the H2O2 level by activating NADPH oxidase. Then, Fc can catalyze the H2O2 to higher cytotoxic hydroxyl radicals (•OH). Moreover, quinone methide (QM) can be produced through H2O2-induced aryl boronic ester rearrangement and further consume the antioxidant GSH. In vitro and in vivo experiments demonstrate that SCSAs can be provided as potential amplified CDT nanoagents.

Highly Stereoselective Synthesis of Tetrasubstituted Vinyl Selenides via Rhodium-Catalyzed [1,4]-Acyl Migration of Selenoesters and Diazo Compounds.

Herein, we disclose a highly stereoselective Rh(II)-catalyzed 1,4-acyl rearrangement of selenium esters and α-diazo carbonyl compounds, which provides an efficient method for synthesizing tetrasubstituted vinyl selenides. Furthermore, this reaction also offers a synthetic tool for medium and large ring compounds.

Diastereoselective Reduction of Selected α-substituted β-keto Esters and the Assignment of the Relative Configuration by 1H-NMR Spectroscopy

Background:: Chiral β-hydroxy esters and α-substituted β-hydroxy esters represent versatile building blocks for pheromones, β-lactam antibiotics and 1,2- or 1,3-aminoalcohols. Objective:: Synthesis of versatile α-substituted β-keto esters and their diastereoselective reduction to the corresponding syn- or anti-α-substituted β-hydroxy esters. Assignment of the relative configuration by NMR-spectroscopy after a Curtius rearrangement of α-substituted β-keto esters to 4-substituted 5-methyloxazolidin-2-ones. Methods: Diastereoselective reduction was achieved by using different Lewis acids (zinc, titanium and cerium) in combination with complex borohydrides as reducing agents. Assignment of the relative configuration was verified by 1H-NMR spectroscopy after Curtius-rearrangement of α-substituted β-hydroxy esters to 4-substituted 5-methyloxazolidin-2-ones. Results:: For the syn-selective reduction, titanium tetrachloride (TiCl4) in combination with a pyridine-borane complex (py BH3) led to diastereoselectivities up to 99% dr. High anti-selective reduction was achieved by using cerium trichloride (CeCl3) and steric hindered reducing agents such as lithium triethylborohydride (LiEt3BH). After Curtius-rearrangement of each α-substituted β-hydroxy ester to the corresponding 4-substituted 5-methyloxazolidin-2-one, the relative configuration was confirmed by 1H NMR-spectroscopy. Conclusion:: We have expanded the procedure of Lewis acid-mediated diastereoselective reduction to bulky α-substituents such as the isopropyl group and the electron withdrawing phenyl ring.

Synthesis of 1,3-diketones via catalytic dehydrogenative rearrangement of esters

In this issue of Chem Catalysis , Kempe and co-workers disclose a general and efficient catalytic synthesis of 1,3-diketones via dehydrogenative rearrangement of esters. The reported process provides an attractive alternative to conventional crossed Claisen condensation, avoiding the generation of alcohol by-products. In this issue of Chem Catalysis , Kempe and co-workers disclose a general and efficient catalytic synthesis of 1,3-diketones via dehydrogenative rearrangement of esters. The reported process provides an attractive alternative to conventional crossed Claisen condensation, avoiding the generation of alcohol by-products.

Synthesis of Morpholinones by Chiral Phosphoric Acid Catalyzed Azabenzilic Ester Rearrangement

Synthesis of Morpholinones by Chiral Phosphoric Acid Catalyzed Azabenzilic Ester Rearrangement

Studies toward norzoanthamine: Ireland–Claisen rearrangements of α,β-unsaturated esters in a stereocontrolled synthesis of trans-fused 2-cyclohexen-1-ones

The enantiocontrolled preparation of the trans-fused ABC ring system of norzoanthamine is described. The synthesis strategy has incorporated studies of Ireland–Claisen rearrangements of esters derived from 3,3-dimethylacrylic acid. Stereocontrol results from competing chair- and boat-like transition states. Introduction of a nitroalkene by application of a modified Henry reaction facilitates an intramolecular Diels–Alder cycloaddition for an effective and simple transformation to the desired conjugated decalone. A fully functionalized AB ring system leads to the cyclization of the trans-fused cyclohexenone to complete the ABC system via ring-closing metathesis.

Synthesis of 1,3-diketones from esters via liberation of hydrogen

Catalytic reactions that convert green or sustainable starting materials into important classes of chemical compounds, generate hydrogen, and are mediated by Earth-abundant element catalysts are highly desirable. Here, we report on a catalytic dehydrogenative rearrangement of esters into 1,3-diketones. Esters are green or sustainable and inexpensive starting materials that are available in great diversity, and 1,3-diketones are highly attractive building blocks for organic synthesis. The concerted interaction of a base-acid catalyst and a dehydrogenation catalyst mediates our reaction. The dehydrogenation catalyst is based on manganese, and the hydrogen formed can be liberated and is the only by-product formed. • Catalytic conversion of green starting materials to important building blocks • Broad product scope and tolerance of many functional groups • Liberation of hydrogen as the only by-product • Application of an Earth-abundant metal catalyst The development of chemistry that reduces CO 2 emission rather than increases it, the sustainable generation of hydrogen, and the conservation of our rare-element resources are key challenges of our time. Therefore, catalytic reactions that convert green or sustainable starting materials into important classes of chemical compounds, generate hydrogen, and are mediated by Earth-abundant element catalysts are highly desirable. Here, we report on a dehydrogenative rearrangement as a combination of a rearrangement reaction and hydrogen generation. The concept permits the general synthesis of 1,3-diketones from esters in the presence of catalysts with hydrogen as the only by-product of the reaction. Mechanistic studies revealed that a dehydrogenation catalyst and a base-acid catalyst are needed to mediate the reaction. The dehydrogenation catalyst we use is based on manganese, the third most abundant transition metal in the Earth’s crust. Esters are sustainable or green starting materials, and 1,3-diketones are highly attractive building blocks for organic synthesis. We developed a novel catalytic synthesis in which 1,3-diketones are formed from esters via dehydrogenation and rearrangement. The key feature of this reaction is the liberation of hydrogen and the use of catalyst based on abundantly available elements.

Catalytic Enantioselective Synthesis of Morpholinones Enabled by Aza-Benzilic Ester Rearrangement.

Chiral morpholinone is an important building block in organic synthesis and a pharmacophore in medicinal chemistry. However, catalytic enantioselective methods for the construction of this N,O-heterocycle remain scarce. We report herein a chiral phosphoric acid-catalyzed enantioselective synthesis of C3-substituted morpholinones from aryl/alkylglyoxals and 2-(arylamino)ethan-1-ols. The reaction proceeds through a domino [4 + 2] heteroannulation followed by a 1,2-aryl/alkyl shift of the resulting cyclic α-iminium hemiacetals. It represents formally an unprecedented asymmetric aza-benzilic ester rearrangement reaction. A concise synthesis of L-742,694, a neurokinin-1 receptor antagonist, featuring this reaction is documented.

Global Diastereoconvergence in the Ireland-Claisen Rearrangement of Isomeric Enolates: Synthesis of Tetrasubstituted α-Amino Acids.

A dual experimental/theoretical investigation of the Ireland-Claisen rearrangement of tetrasubstituted α-phthalimido ester enolates to afford α-tetrasubstituted, β-trisubstituted α-amino acids (generally >20:1 dr) is described. For trans allylic olefins, the Z- and E-enol ethers proceed through chair and boat transition states, respectively. For cis allylic olefins, the trend is reversed. As a result, the diastereochemical outcome of the reaction is preserved regardless of the geometry of the enolate or the accompanying allylic olefin. We term this unique convergence of all possible olefin isomers global diastereoconvergence. This reaction manifold circumvents limitations in present-day technologies for the stereoselective enolization of α,α-disubstituted allyl esters. Density functional theory paired with state-of-the-art local coupled-cluster theory (DLPNO-CCSD(T)) was employed for the accurate determination of quantum mechanical energies.

4-Hydroxy Pyridinium Triflate@SiO2 Nanoparticles as a Novel Efficient Catalyst for Fries Rearrangement of Aryl Esters with High Selectivity.

We developed a simple, fast and new method for the Fries rearrangement of aryl esters. 4-Hydroxy pyridinium triflate functionalized silica is a very efficient, reusable and economically available catalyst for the Fries rearrangement in solvent-free condition and under microwave irradiation. Also, a notable selectivity was observed in the presence of 4-hydroxy pyridinium triflate functionalized silica. Selectivity, shorter reaction time, high yield, and easy work-up are advantages of this synthetic method.