Base-mediated Reaction Research Articles

Catalytic Inhibition of Base-Mediated Reactivity by a Self-Assembled Metal-Ligand Host.

Spacious M4 L6 tetrahedra can act as catalytic inhibitors for base-mediated reactions. Upon adding only 5 % of a self-assembled Fe4 L6 cage complex, the conversion of the conjugate addition between ethylcyanoacetate and β-nitrostyrene catalyzed by proton sponge can be reduced from 83 % after 75 mins at ambient temperature to <1 % under identical conditions. The mechanism of the catalytic inhibition is unusual: the octacationic Fe4 L6 cage increases the acidity of exogenous water in the acetonitrile reaction solvent by favorably binding the conjugate acid of the basic catalyst. The inhibition only occurs for Fe4 L6 hosts with spacious internal cavities: minimal inhibition is seen with smaller tetrahedra or Fe2 L3 helicates. The surprising tendency of the cationic cage to preferentially bind protonated, cationic ammonium guests is quantified via the comprehensive modeling of spectrophotometric titration datasets.

Rapid assembly of structurally diverse cyanamides and disulfanes via base-mediated aminoalkylation of aryl thiourea

A general one-pot method for the preparation of cyanamides and disulfanes from aryl thioureas and halides via a base-mediated reaction was accomplished.

Chemoselective and one-pot synthesis of novel coumarin-based cyclopenta[c]pyrans via base-mediated reaction of α,β-unsaturated coumarins and β-ketodinitriles.

In this paper, the base-mediated cascade reactions of 4-chloro-3-vinyl coumarins with β-ketodinitriles were demonstrated, allowing the efficient synthesis of coumarin-based cyclopenta[c]pyran-7-carbonitriles with interesting chemoselectivity. These transformations include the domino-style formation of C–C/C–C/C–O bonds through a base-mediated nucleophilic substitution, Michael addition, tautomerization, O-cyclization, elimination, and aromatization. The presented synthetic strategy has many advantages such as simple and readily available starting materials, green solvent, highly chemoselective route, synthetically useful yields, and easy purification of products by washing them with EtOH (96%), described as GAP (Group-Assistant-Purification) chemistry.

2,2′-(1,4-Phenylene)bis(7-nitro-1H-benzimidazole 3-oxide)

Bis(benzimidazol-2-yl-3-oxide)benzene derivatives have potential applications as energetic or photoactive materials. By using a two-step one-pot approach employing microwave heating as a tool, 2,2′-(1,4-phenylene)bis(7-nitro-1H-benzimidazole 3-oxide) (1) has been prepared in 94% yield. In the first step an SNAr reaction is performed using p-xylylenediamine as the central building block. Without isolating the intermediate, a base-mediated cyclization reaction follows in the second step. The product was isolated in analytically pure form by means of a pH-controlled precipitation.

Base-mediated reactions of diethyl malonates derivatives with perfluorinated olefins: Novel synthetic routes to multifunctional ionomer precursors

A novel synthetic method for the preparation of per- and polyfluorinated unsaturated 2-substituted malonates is presented involving the deprotonation of the starting diethyl malonate by a strong base, followed by in situ addition of the C-nucleophile to the terminal double bond of the perfluorinated olefin. Subsequent elimination of the corresponding leaving groups and restoring of the double bond leads to the target bifunctional perfluorinated olefins. In the case of unsubstituted diethyl malonate, the elimination is accompanied by a prototropic rearrangement with a double bond migration and the addition of a second equivalent of the C-nucleophile forming the tetrafunctional internal olefins. The reaction conditions, factors affecting the reactivity and regioselectivity of the process, the choice of reagent as well as the course of competitive reactions are also discussed.

Difunctionalization of Alkynones by Base-Mediated Reaction with α,α-Dithioketones.

A novel 1,2-difunctionalization of alkynones via an umpolung strategy for the synthesis of tetrasubstituted olefins has been developed. This procedure is realized by a formal C-C σ-bond cleavage reaction of cyclic α,α-dithioketones and subsequent deprotection. Notable features of this approach include excellent yields, mild reaction conditions, a broad substrate scope, and operational simplicity.

A Study of [3+2] Cycloaddition Reaction of Hydrazonoyl Chloride and β‐Oxodithioester Under Lewis Acid Catalysis: Stereoselective Synthesis of (Z)‐1,3,4‐Thiadiazol‐2(3H)‐Ylidenes.

AbstractHydrazonoyl chlorides underwent unprecedented stereoselective [3+2] cycloaddition reaction with β‐oxodithioesters and β‐oxothioamides under Lewis acid catalysis producing (Z)‐1,3,4‐ thiadiazol‐2(3H)‐ylidenes in high yields. These products are obtained also with a base. Though same products are obtained in both these conditions, they involve different reaction mechanisms. In base mediated reactions, 1,3‐dipolar cycloaddition of a nitrilimine to C=S is operative and in Lewis acid catalysed reactions, β‐oxodithioester/β‐oxothioamide undergoes addition‐cyclization reactions with a hydrazonoyl chloride.

Efficient synthesis of seven-membered Aza-sultams: Heterofused amino-1,2,4-thiadiazepine dioxides

An efficient synthesis of 7-membered Aza -sultams bearing heterofused amino-1,2,4-thiadiazepine framework have been developed. Functional group pairing strategy using ambiphilic building blocks such as 1 H -azole-2-carbonitrile and N -(chloromethyl)- N -methylmethanesulfonamide in the two-step base-mediated reaction sequence was described. The synthetic utility of the obtained Aza-sultams was demonstrated by hydrolysis, reduction, and cross-coupling reactions. A cascade reaction involving β -enamine sulfonamide moiety within sultam ring in the synthesis of fused pyridine heterocycle has been investigated. It should be noted that β -enamine scaffolds among ε-sultams have been first synthesized via the cyclization approach.

Synthesis of aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers through the base-mediated reaction between phenols and halothane.

An efficient and convenient method for the synthesis of structurally unique and highly functionalized aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers has been developed. This approach exhibits a broad reaction scope, a simple operation and without the need of any expensive transition-metal catalyst, highly toxic or corrosive reagents. Notably, we demonstrate the potential utility of halothane for the synthesis of aryl gem-difluoroalkyl ethers containing the bromochloromethyl group.

Carbon monoxide and hydrogen (syngas) as a C1-building block for selective catalytic methylation.

A catalytic reaction using syngas (CO/H2) as feedstock for the selective β-methylation of alcohols was developed whereby carbon monoxide acts as a C1 source and hydrogen gas as a reducing agent. The overall transformation occurs through an intricate network of metal-catalyzed and base-mediated reactions. The molecular complex [Mn(CO)2Br[HN(C2H4PiPr2)2]] 1 comprising earth-abundant manganese acts as the metal component in the catalytic system enabling the generation of formaldehyde from syngas in a synthetically useful reaction. This new syngas conversion opens pathways to install methyl branches at sp3 carbon centers utilizing renewable feedstocks and energy for the synthesis of biologically active compounds, fine chemicals, and advanced biofuels.

Regioselective synthesis of functionalized pyrazole-chalcones via a base mediated reaction of diazo compounds with pyrylium salts.

A base-mediated reaction of triaryl/alkyl pyrylium tetrafluoroborate salts with α-diazo-phosphonates, sulfones and trifluoromethyl compounds affords the corresponding functionalized pyrazole-chalcones as 5-P-5 and 3-P-3 tautomeric mixture. The reaction proceeds through an initial nucleophilic addition of diazo substrates to pyrylium salts followed by a base-mediated pyrylium ring-opening and intramolecular 1,5-cyclization to afford formal 1,3-dipolar cycloaddition products. The products underwent a Nazarov-type cyclization upon hydride reduction followed by acidic-workup, furnishing the corresponding indenyl-pyrazoles in high yields.

Regioselective synthesis of substituted cyclohexa-1,3-dienes via the base-mediated cyclisation of α,β-unsaturated carbonyl compounds and γ-phosphonylcrotonates

The base-mediated reaction of α,β-unsaturated carbonyl compounds and γ-phosphonylcrotonates under an argon atmosphere readily furnishes substituted cyclohexa-1,3-dienes. The cyclisation proceeds with complete regioselectivity to afford products that are readily amenable to further redox manipulations. The presented method allows the rapid and regioselective syntheses of six-membered carbocycles at three different oxidation levels.

Dihydro-2H-thiopyran-3(4H)-one-1,1-dioxide – a new cyclic ketomethylenic reagent for the Dimroth-type 1,2,3-triazole synthesis

A series of 1,5,6,7-tetrahydrothiopyrano[2,3-d][1,2,3]triazole 4,4-dioxides, new triazole-based bicyclic ring system, were prepared via base-mediated click reaction of organic azides with the readily available dihydro-2H-thiopyran-3(4H)-one-1,1-dioxide. The reaction proceeded at room temperature in 5-12 h with catalysis by base-solvent system K2CO3/DMSO. High purity products were isolated by simple filtration and no formation of side products was observed. The key structure was confirmed by an X-ray study.

An access to α, β-unsaturated ketones via dual cooperative catalysis

A dual cooperative organocatalytic approach for the synthesis of α, β-unsaturated ketones is described. This one pot transformation is realized via a domino Knoevenagel-Michael-retro Michael reaction sequence. Various aliphatic ketones reacted smoothly with aromatic as well as aliphatic aldehydes in presence catalytic amount of Meldrum’s acid and bifunctional amine. The highlights of this protocol are the easy availability of catalysts, high selectivity, and functional group tolerance. The reaction proved to highly E-selective with no side products emanating from self-condensation, unlike the base-mediated reactions.

One-Pot Synthesis of Dibenzo[ b, d]oxepines via Olefinic C-F Bond Functionalization and Intramolecular Pd-Catalyzed C-H Arylation.

We report base-mediated reactions of 1-bromo-2-(2,2-difluorovinyl)benzenes with phenols followed by Pd-catalyzed intramolecular C-H arylation, which offers a novel route to a pharmaceutically relevant class of compounds, oxepines. Construction of these medium-sized ring structures proceeds as a one-pot two-step reaction through diaryl ketene acetals as intermediates. It allows to obtain various dibenz[ b, d]oxepine derivatives in moderate to high yields.

Direct Carboxylation of C(sp3)-H and C(sp2)-H Bonds with CO2 by Transition-Metal-Catalyzed and Base-Mediated Reactions

This review focuses on recent advances in the field of direct carboxylation reactions of C(sp3)-H and C(sp2)-H bonds using CO2 encompassing both transition-metal-catalysis and base-mediated approach. The review is not intended to be comprehensive, but aims to analyze representative examples from the literature, including transition-metal catalyzed carboxylation of benzylic and allylic C(sp3)-H functionalities using CO2 which is at a “nascent stage”. Examples of light-driven carboxylation reactions of unactivated C(sp3)-H bonds are also considered. Concerning C(sp3)-H and C(sp2)-H deprotonation reactions mediated by bases with subsequent carboxylation of the carbon nucleophile, few examples of catalytic processes are reported in the literature. In spite of this, several examples of base-promoted reactions integrating “base recycling” or “base regeneration (through electrosynthesis)” steps have been reported. Representative examples of synthetically efficient, base-promoted processes are included in the review.

ChemInform Abstract: Catalytic Asymmetric Synthesis of Bicycloprolines by a 1,3‐Dipolar Cycloaddition/Intramolecular Alkylation Strategy.

The diastereoselective one-pot synthesis of hexahydrocyclopenta[b]pyrrole derivatives (bicycloprolines) has been achieved by base-mediated reactions of (E)-tert-butyl 6-bromo-2-hexenoate with α-imino esters. The catalytic asymmetric version of this process has been efficiently achieved using the CuI/(R)-DTBM-Segphos complex as a catalyst following a two-step 1,3-dipolar cycloaddition/intramolecular alkylation sequence.

Catalytic Asymmetric Synthesis of Bicycloprolines by a 1,3-Dipolar Cycloaddition/Intramolecular Alkylation Strategy.

The diastereoselective one-pot synthesis of hexahydrocyclopenta[b]pyrrole derivatives (bicycloprolines) has been achieved by base-mediated reactions of (E)-tert-butyl 6-bromo-2-hexenoate with α-imino esters. The catalytic asymmetric version of this process has been efficiently achieved using the Cu(I)/(R)-DTBM-Segphos complex as a catalyst following a two-step 1,3-dipolar cycloaddition/intramolecular alkylation sequence.

Transition-Metal-Free Synthesis of Homo- and Hetero-1,2,4-Triaryl Benzenes by an Unexpected Base-Promoted Dearylative Pathway.

An unprecedented approach for the synthesis of homo- and hetero-1,2,4-triaryl benzenes has been developed using a simple base-mediated reaction of either α-aryl cinnamyl alcohols or α,γ-di-aryl propanones. The salient feature of this strategy involves the sequential hydride transfer, regiospecific condensation, regiospecific dearylation, and aromatization under metal-free reaction conditions. The synthesis of unsymmetrically substituted triphenylenes by oxidative coupling of the synthesized 1,2,4-triaryl benzenes has also been demonstrated.

Mechanochemical solid-state synthesis of 2-aminothiazoles, quinoxalines and benzoylbenzofurans from ketones by one-pot sequential acid- and base-mediated reactions.

α-Chloroketones - obtained by the atom-economical chlorination of ketones with trichloroisocyanuric acid (TCCA) in the presence of p-TSA under ball-milling conditions - were set up for a sequential base-mediated condensation reaction with thiourea/thiosemicarbazides, o-phenylenediamine and salicylaldehyde to afford 2-aminothiazoles, 2-hydrazinylthiazoles, quinoxalines and benzoylbenzofurans, respectively, in respectable yields. The viability of one-pot sequential acid- and base-mediated reactions in the solid state under ball-milling conditions is thus demonstrated.