Transacylation. Biomimetic synthesis of esters of acetic acid

By mixing of β‐hydroxypropyl phosphate and acetic acid in ethanol solution, ethyl acetate is produced. As found, acetyl phosphate is first formed, then it reacts with the solvent to give the final ethyl acetate product. By similar procedures, acetates of methanol, n‐propanol, and n‐butanol are also produced. Propylene oxide serves as a condensing agent. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:350–352, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20216     

A convenient synthesis of 2-methyl-3-oxoheptane-1,7-dicarboxylic esters and amides

A range of simple derivatives of 2-methyl-3-oxoheptane-1,7-dicarboxylic acid have been prepared by Birch reduction/methylation of 2,6-dimethoxybenzoic acid derivatives followed by solvolysis.     

Palladium-catalyzed synthesis of substituted cyclopentadienes and indenes from allylic esters

Various mono- and di-substituted cyclopentadienes have been prepared by palladium-catalyzed alkylation of allylic esters with cyclopentadienide and t-butyl-cyclopentadienide anions. The same procedure has been applied to the preparation of substituted indenes.     

The stobbe condensation with substituted succinic esters. II A synthesis of benzothiophene derivatives

The condensation of some thienyl carbonyl compounds with dimethyl phenylsuccinate using either sodium hydride or potassium t-butoxide as condensing agents, gave a stereoisomeric mixture of (E)- and (Z)-half-esters (3). The (E)-half-esters la-c were either cyclised to the corresponding benzothiophene derivatives or hydrolysed to the (E)-dibasic acids VIa-e, which were cyclised to the corresponding anhydrides VIIa-c. Methylation of VIIa,c gave the isomeric half-esters VIIIa,c. The (Z)-half-ester Id can cyclise easily to the lactone IX.     

A new one-pot synthesis of difluoro(organylsulfinyl)acetic acid esters

A novel single-step method for the synthesis of esters of difluoro(organylsulfinyl)acetic acids, by reacting aromatic compounds with isopropyl chlorosulfinyldifluoroacetate, was developed. The feasibility of transforming the sulfoxide intermediates into corresponding sulfides and sulfones was demonstrated.     

The synthesis of 2-ketopiperazine acetic acid esters and amides from ethylenediamines with maleates and maleimides

The reaction of substituted ethylenediamines with various fumarates, maleates, and maleimides to form substituted ketopiperazine acetic acid esters and amides was investigated. This method affords a straightforward, high yield approach to a variety of potential peptidomimetics and can yield surprising results with regard to regio- and stereoselectivity.     

The first synthesis of N-acetylneuraminic acid 1,7-lactone

N-Acetylneuraminic acid is transformed into its until now unavailable and rather unwieldy 1,7-lactone, via the manageable 2-benzyloxycarbonyl N-acetylneuraminic acid 1,7-lactone which generates the free lactone in quantitative yield by hydrogenolysis.     

Convenient synthesis of electron-donating substituted benzonitriles by photolysis of phenyl halides and esters

Irradiation of electron-donating substituted phenyl halides (fluorides and chlorides) or esters (mesylates, triflates and phosphates) in aqueous MeCN in the presence of KCN gives the corresponding benzonitriles in 48 to 100% yield through an ArSN1 reaction with the intermediacy of a triplet phenyl cation.     

An unusual dianion equivalent from acylsilanes for the synthesis of substituted beta-keto esters

The reaction of lithiated diazo esters with acylsilanes generates a remarkable intermediate en route to highly substituted beta-keto esters.     

Sulfur(iv) reagents for the SuFEx-based synthesis of substituted sulfamate esters

Sulfur(vi) fluoride exchange chemistry has been reported to be effective at synthesizing valuable sulfur(vi) functionalities through sequential nucleophilic additions, yet oxygen-based nucleophiles are limited in this approach to phenolic derivatives. Herein, we report a new sulfur(iv) fluoride exchange strategy to access synthetically challenging substituted sulfamate esters from alkyl alcohols and amines. We also report the development of a non-gaseous, sulfur(iv) fluoride exchange reagent, N-methylimidazolium sulfinyl fluoride hexafluorophosphate (MISF). By leveraging the reactivity of the sulfur(iv) center of this novel reagent, the sequential addition of alcohols and amines to MISF followed by oxidation afforded the desired substituted sulfamates in 40–83% yields after two steps. This new strategy expands the scope of SuFEx chemistry by increasing the accessibility of underdeveloped –S(O)F intermediates for future explorations.

N-Methylimidazolium sulfinyl fluoride hexafluorophosphate (MISF) was developed as a solution-stable sulfur(iv) reagent to access substituted sulfamate esters using a sulfur(iv) fluoride exchange strategy.

Sulfur fluoride exchange (SuFEx) reagents have powerful applications in pharmaceuticals, chemical biology, and materials science.¹ The most commonly utilized reagents are sulfur(vi) compounds, such as sulfuryl fluoride (SO₂F₂) and its derivatives, that can be used to efficiently synthesize a wide range of functionalities through sequential nucleophilic additions (Fig. 1a).² Sulfamate esters are targets of particular interest as they display potential as anticancer agents and as a new class of antibiotics,³ as well as versatility as synthetic intermediates.⁴ Oxygen-based nucleophiles are limited to phenolic derivatives with sulfur(vi) SuFEx reagents, restricting their use in sulfamate ester syntheses. The reaction of aliphatic alcohols with SO₂F₂ leads to aliphatic fluorosulfate intermediates that are very unstable, and results in rapid substitution at the fluorosulfate alpha-position (Fig. 1b).^5,6O-Alkyl sulfamate esters (ROSO₂NH₂) are readily synthesized with alternatives to SuFEx-based methods,⁷ but the substituted analogues require harsh conditions, multiple steps, and long reaction times.⁸ For example, sulfur(vi) chloride reagents have been utilized in the syntheses of sulfur(vi) moieties, yet are limited due to their inherent instability and prevalent side reactions.^9,10 A fast, mild, and SuFEx-based approach to the syntheses of substituted alkyl sulfur(vi) motifs is, therefore, desired.Open in a separate windowFig. 1SuFEx chemistry for the syntheses of S(vi) functionalities. (a) Reported sulfur(vi) SuFEx approach to linking nucleophiles. (b) Limitations of sulfur(vi) reagents in accessing fluorosulfate intermediates. (c) This work. Use of novel sulfur(iv) SuFEx reagent followed by oxidation to access synthetically challenging sulfur(vi) motifs that are inaccessible with sulfur(vi) reagents.The aforementioned limitations of sulfur(vi) SuFEx reactions may be overcome by utilizing a novel approach involving sulfur(iv) fluoride reagents (Fig. 1d). The addition of an alkyl alcohol to a sulfur(iv) fluoride exchange reagent should readily form the corresponding fluorosulfite intermediate. In contrast to fluorosulfates, fluorosulfites 2 may be more reactive at the sulfur center than the alpha-position.¹¹ Therefore, the addition of a heteroatom nucleophile to the sulfur(iv) center of a fluorosulfite should be faster and more selective than the sulfur(vi) analogue. A subsequent oxidation of the sulfur(iv) center would then afford the desired sulfur(vi) motif. While the oxidation step limits the substrate scope, this strategy provides a route to substrates that were previously inaccessible.Thionyl fluoride (SOF₂), the sulfur(iv) analogue of SO₂F₂, has displayed versatile reactivity despite the relatively few studies on its use.^11,12 The initial addition of a heteroatomic nucleophile to thionyl fluoride has been reported to be an efficient protocol for achieving amino sulfinyl fluorides and fluorosulfites,¹³ yet further reactivity of these intermediates has not been reported. There are also several major drawbacks to its use, including safety hazards associated with handling the gaseous reagent.¹⁴ There is no literature precedence for non-gaseous sulfur(iv) derivatives of thionyl fluoride. Therefore, a non-gaseous derivative that maintains the fundamental reactivity of SOF₂ is essential for the broad adoption of this class of sulfur(iv) reagents.     

Activated esters of substituted pyrazinecarboxylic acids

N-Amidino-3,5-diamino-6-chloropyrazinecarboxamide ( 1 ) has been shown to be an effective potassium sparing diuretic. Various carboxyl activating agents have been employed with 3-amino-pyrazinecarboxylic acids in an effort to synthesize analogs of 1. Stable enol esters were isolated from a number of such acids and N-t-butyl-5-methylisoxazolium perchlorate ( 12 ). Although strong bases in DMF or DMSO catalyze a competing destruction of the enol ester system, these esters are useful acylating agents for a variety of nucleophilic substrates in less polar media. Amides, esters, and thiol esters are produced in good yields under mild conditions from these activated esters.     

Synthesis of substituted 2-cyanoarylboronic esters

The synthesis of substituted 2-cyanoarylboronic esters is described via lithiation/in situ trapping of the corresponding methoxy-, trifluoromethyl-, fluoro-, chloro-, and bromobenzonitriles. The crude arylboronic esters were obtained in high yields and purities and with good regioselectivities.     

Syngas reactions XII. The selective preparation of acetaldehyde,alkanols, esters and acetic acid from synthesis gas

Several classes of commercially important oxygenates, including acetaldehyde, ethanol, methyl acetate, ethyl acetate and acetic acid as well as C₁–C₃ alcohol/acetate ester mixtures, may each be selectivelygenerated from synthesis gas through the application of novel classes of ruthenium-containing bimetallic catalysts particularly those of ruthenium and cobalt (Ru? Co). A particular feature of these versatile catalysts is that all precursors are iodidefree. Products are formed through a combination of carbon monoxide hydrogenation, methanol homologation, methyl acetate homologation and methanol carbonylation reaction sequences.     

Diastereoselective synthesis of substituted tetrahydroquinoline-4-carboxylic esters by a tandem reduction-reductive amination reaction

A diastereoselective synthesis of 1-methyl-2-alkyl- and 2-alkyl-1,2,3,4-tetrahydroquinoline-4-carboxylic esters has been developed from methyl (2-nitrophenyl)acetate (1). The method involves alkylation of 1 with an allylic halide, ozonolysis of the double bond, and catalytic hydrogenation. The final hydrogenation initiates a tandem sequence involving (1) reduction of the aromatic nitro group, (2) condensation of the aniline or hydroxylamine(8) nitrogen with the side chain carbonyl, (3) reduction of the resulting nitrogen intermediate, and (4) reductive amination of the tetrahydroquinoline with formaldehyde produced in the ozonolysis to give a methyl (+/-)-1-methyl-2-alkyl-1,2,3,4-tetrahydroquinoline-4-carboxylate. Removal of the formaldehyde prior to hydrogenation gives the simple (+/-)-2-alkyl derivatives. The products are isolated in high yield as single diastereomers having the C-2 alkyl group cis to the C-4 carboxylic ester. The reaction has been extended to the synthesis of tricyclic structures with similar high diastereoselection.     

The synthesis of substituted 2-aminothiazoles

The preparation of 4- and 5-acyl- and aroyl-2-substituted aminothiazoles is described. The condensation of thioureas with acyl halides leading to 4,5-disubstituted-2-aminothiazoles and 7-(4H)benzothiazolones is discussed. A discussion of the isolation of various intermediates and the mechanistic pathway is also included. A number of 2-anilino or 2-benzyl-4- or 5-aroylthiazoles possessed moderate oral antitubercolosis activity ( 2 ).     

The synthesis of substituted 8-quinolinols

2-Isopropyl-8-quinolinol was prepared by alkylation of 8-methoxyquinoline followed by demethylation. The 7-isopropyl-8-quinolinol was prepared in three steps from o-isopropylphenol. The reaction of 5-chloromethyl-8-quinolinol hydrochloride with alcohols, amines, ethylene glycols and ether-alcohols gave the corresponding 5-substituted derivatives of 8-quinolinol.     

The synthesis of substituted 1,5-benzodiazepines

The synthesis of some substituted 1,5-benzodiazepines are described. The route is based on the reaction between 1,4-phenylenediamine and its derivative with crotonic acid or methacrilic acid.