Organocatalytic Enantioselective Decarboxylative Reaction of Malonic Acid Half Thioesters with Cyclic N‐Sulfonyl Ketimines by Using N‐Heteroarenesulfonyl Cinchona Alkaloid Amides

The organocatalytic enantioselective decarboxylative Mannich reaction of malonic acid half thioesters (MAHTs) with cyclic N‐sulfonyl ketimines by using N‐heteroarenesulfonyl cinchona alkaloid amides afforded products with high enantioselectivity. Both enantiomers of the products could be obtained by using pseudoenantiomeric chiral catalysts. The reaction proceeds through a nucleophilic addition of the MAHTs to the ketimines prior to decarboxylation.     

Enantioselective synthesis of AG-041R by using N-heteroarenesulfonyl cinchona alkaloid amides as organocatalysts

The organocatalytic enantioselective decarboxylative addition of malonic acid half thioesters to ketimines derived from isatins by using N-heteroarenesulfonyl cinchona alkaloid amides afforded products with high enantioselectivity. The products could be converted into optically active AG-041R. X-ray crystallographic analysis revealed that the hydrogen bonding between the sulfonimide proton and the 8-quinolyl nitrogen atom plays an important role in exerting the enantioselectivity of the reaction.     

Catalytic enantioselective thioester aldol reactions that are compatible with protic functional groups

This communication reports highly enantioselective and diastereoselective methyl malonic acid half thioester (MeMAHT) aldol reactions that are compatible with protic functional groups and enolizable aldehydes, affording syn S-phenyl thiopropionates.     

Enantioselective Synthesis of AG‐041R by using N‐Heteroarenesulfonyl Cinchona Alkaloid Amides as Organocatalysts

The organocatalytic enantioselective decarboxylative addition of malonic acid half thioesters to ketimines derived from isatins by using N‐heteroarenesulfonyl cinchona alkaloid amides afforded products with high enantioselectivity. The products could be converted into optically active AG‐041R. X‐ray crystallographic analysis revealed that the hydrogen bonding between the sulfonimide proton and the 8‐quinolyl nitrogen atom plays an important role in exerting the enantioselectivity of the reaction.     

Convenient and efficient decarboxylative aldol reaction of malonic acid half esters with trifluoromethyl ketones

A convenient and efficient decarboxylative ketone aldol condensation of malonic acid half esters was reported. In the presence of catalytic amount of triethylamine, a series of aromatic and alkyl trifluoromethyl ketones were transformed into the desired adducts in 61–99% yields. In a preliminary experiment, a moderate stereoselectivity was obtained. Direct reduction of the aldol product with LiAlH₄ afforded trifluoromethylated 1,3-diol.     

Expanding the utility of Brønsted base catalysis: biomimetic enantioselective decarboxylative reactions

As a result of the low reactivity of simple esters, the use of them as nucleophiles in direct asymmetric transformations is a long-standing challenge in synthetic organic chemistry. Nature approaches this difficulty through a decarboxylative mechanism, which is used for polyketide synthesis. Inspired by nature, we report guanidine-catalyzed biomimetic decarboxylative C-C and C-N bond-formation reactions. These highly enantioselective decarboxylative Mannich and amination reactions utilized malonic acid half thioesters as simple ester surrogates. It is proposed that nucleophilic addition precedes decarboxylation in the mechanism, which has been investigated in detail through the identification of intermediates by using electrospray ionization (ESI) mass-spectrometric analysis and DFT calculations.     

Asymmetric Decarboxylative 1,4‐Addition of Malonic Acid Half Thioesters to Vinyl Sulfones: Highly Enantioselective Synthesis of 3‐Monofluoromethyl‐3‐Arylpropanoic Esters

An asymmetric decarboxylative 1,4‐addition of malonic acid half thioesters (MAHTs) to 2‐aryl‐substituted vinyl sulfones has been developed, yielding adducts with excellent enantioselectivity (up to 97 % ee). In view of tuning pK_a values, a quinine‐based benzyl‐substituted thiourea was designed and demonstrated as the most efficient catalyst. The enantioselective synthesis of 3‐monofluorinated analogues of 3‐methyl indanone and (+)‐turmerone has been accomplished from decarboxylative 1,4‐addition adducts with satisfactory results.     

One-pot enol silane formation-Mukaiyama aldol reactions: Crossed aldehyde-aldehyde coupling,thioester substrates,and reactions in ester solvents

Trimethylsilyl trifluoromethanesulfonate (TMSOTf) and a trialkylamine base promote both in situ enol silane/silyl ketene acetal formation and Mukaiyama aldol addition reactions between a variety of reaction partners in a single reaction flask. Isolation of the required enol silane or silyl ketene acetal is not necessary. For example, crossed aldol reactions between α-disubstituted aldehydes and non-enolizable aldehydes yield β-hydroxy aldehydes in good yield. In a related reaction, the common laboratory solvent ethyl acetate functions as both an enolate precursor and a green reaction solvent. When thioesters are employed as enolate precursors, high yields for additions to non-enolizable aldehydes are routinely observed.     

Synthesis of Monothiomalonates – Versatile Thioester Enolate Equivalents for C–C Bond Formations

Monothiomalonates (MTM s) are surrogates of thioester enolates that allow for stereoselective C–C bond formations under mild conditions and thereby afford access to synthetically versatile thioester derivatives. Here we present a straightforward synthetic route to MTM s that proceeds through nucleophilic ring‐opening of Meldrum 's acid derivatives followed by O‐alkylation of the resulting malonic acid half thioesters with alkyl triflates or acetimidates as electrophiles. The method affords MTM s in overall yields of 34 – 92% and allows for variations of the oxo‐ and thioester moieties as well as the substituent at the C(α ) position.     

A facile and efficient direct aldol addition of simple thioesters

[reaction: see text] Simple thioesters undergo direct aldol addition to aldehydes in the presence of MgBr(2).OEt(2) and i-Pr(2)NEt using untreated, reagent-grade CH(2)Cl(2) under atmospheric conditions. The reactions proceed extremely rapidly and in excellent yield.     

Direct carbon-carbon bond formation via soft enolization: aldol addition of α-halogenated thioesters

α-Halo thioesters undergo soft enolization and syn-selective direct aldol addition to aldehydes in the presence of MgBr(2)·OEt(2) and i-Pr(2)NEt to produce α-halo-β-hydroxy thioesters.     

α,β-不饱和羰基化合物的合成研究进展

α,β-不饱和羰基化合物是制备多种新型驱油材料的重要中间体,可以通过偶联、加成等反应实现功能材料分子官能团的多样化、结构的多元化以及材料性能的高效化。对α,β-不饱和羰基化合物的合成方法(羟醛缩合反应、丙二酸加成-脱羧反应、斯托伯反应、Knoevengel反应、Reformasky反应、曼尼希反应等)进行了综述。参考文献30篇。     

Rhodium-catalyzed interconversion between acid fluorides and thioesters controlled using heteroatom acceptors

A rhodium complex catalyzed the equilibrium acyl transfer reaction between acid fluorides and thioesters. In the presence of fluoride or thiolate acceptors, the reaction could be shifted to either product. RhH(PPh₃)₄-dppe catalyzed the reaction of acid fluorides and diorgano disulfides in the presence of triphenylphosphine giving thioesters, which was accompanied by triphenylphosphine difluoride. The same complex catalyzed the reaction of aryl thioesters and hexafluorobenzene giving acid fluorides, which was accompanied by 1,4-di(arylthio)-2,3,5,6-tetrafluorobenzenes.     

Readily available (S)-proline-derived organocatalysts for the Lewis acid-mediated Lewis base-catalyzed stereoselective aldol reactions of activated thioesters

A set of enantiomerically pure Lewis bases containing different diphenyl phosphinyl oxide groups were easily synthesized in a straightforward procedure by reaction of readily available proline-based scaffolds and phosphinoyl chlorides. The newly synthesized derivatives were employed (0.1 mol equiv) as organocatalysts in the Lewis acid-mediated Lewis base-promoted direct stereoselective aldol reactions of activated thioesters with aromatic aldehydes, carried out in the presence of tetrachlorosilane and a tertiary amine. β-Hydroxy thioesters were obtained in moderate to high yields, with very high syn diastereoselectivities (dr up to >98:2), and fair enantioselectivities (ee up to 51%). Theoretical studies were performed in order to elucidate the origin of the stereoselection.     

Conjugate reduction and reductive aldol cyclization of α,β-unsaturated thioesters catalyzed by (BDP)CuH

A conjugate reduction of α,β-unsaturated thioesters catalyzed by copper hydride using PMHS as stoichiometric reductant has been developed. 1,2-Bis(diphenylphosphino)benzene (BDP) was the most effective ligand for this reduction. Saturated thioesters could be produced in excellent yields when the substituent on the thiol is not sterically-demanding. This protocol was applied to induce the reductive aldol cyclization of keto-enethioates, which could offer β-hydroxythioesters in moderate to good yields.     

Stereoselective aldol condensations via alkenyloxy dialkoxyboranes: synthetic applications using thioesters

A detailed Investigation of the enolization of phenyl thiopropionate with ethylenechloroboronate (ECB) and diisopropylethylamine (DPEA) and the subsequent aldol condensations of these enolates was conducted. Alkenyloxy dialkoxyboranes derived from thioesters were found to be stereoconvergent: both Z and E enolates give syn aldol condensation products. The thioester additions to chiral aldehydes were studied. Internal selectivity (syn) was usually very high, while the relative stereoselectivity ranged from poor to good, depending on the specific aldehyde used. The aldol products were transformed to known compounds for correlation.     

Self-condensation of activated malonic acid half esters: a model for the decarboxylative Claisen condensation in polyketide biosynthesis

The reaction of a malonic acid half oxyester with a N-hydroxysuccinimidyl ester-forming reagent resulted in self-condensation to provide the corresponding 1,3-acetonedicarboxylic acid diester. This new method does not require a divalent metal chelator or a coordinating solvent for successful condensation.     

Overcoming the limitations of the Morita-Baylis-Hillman reaction: a rapid and general synthesis of alpha-alkenyl-beta'-hydroxy thioesters

Acryloyl chlorides, aldehydes, and PhSLi undergo a direct aldol cascade sequence in the presence of MgBr2 x OEt2 via in situ derived thioester enolates, which is followed by oxidative elimination to give alpha-alkenyl-beta'-hydroxy thioesters. Overall, the procedure is rapid, efficient, and generally applicable, even to beta-substituted acryloyl chlorides, thus providing an alternative to the Morita-Baylis-Hillman reaction with substantially greater synthetic scope and utility.     

Equilibrium shift in the rhodium-catalyzed acyl transfer reactions

Rhodium/phosphine complexes catalyze equilibrium acyl transfer reactions between acid fluorides, aryl esters, acylphosphine sulfides, and thioesters. The use of appropriate co-substrates to accept heteroatom groups shifted the equilibrium to desired products. Acylphosphine sulfides and aryl esters were converted to acid fluorides using benzoylpentafluorobenzene as the fluoride donor, and the fluorination reaction of thioesters employed (4-tolylthio)pentafluorobenzene. Acid fluorides were converted into acylphosphine sulfides and thioesters using diphosphine disulfides and disulfides/triphenylphosphine, respectively. Aryl esters were obtained from acid fluorides and phenols in the presence of triphenylsilane. Aryl esters, acylphosphine sulfides, and thioesters were also interconverted in the presence of rhodium complexes. These rhodium-catalyzed acyl transfer reactions proceeded under neutral conditions without using acid or base. The involvement of acyl rhodium intermediates in these reactions was suggested by the carbothiolation reaction of thioesters and alkynes.     

Contribution to the chemistry of the Belousov-Zhabotinsky reaction. Products of the Ferriin-Bromomalonic acid and the Ferriin-Malonic acid reactions

In the present mechanistic schemes of the ferroin-catalyzed oscillatory Belousov-Zhabotinsky (BZ) reaction the oxidation of the organic substrates (bromomalonic or malonic acid) by ferriin (the oxidized form of the catalyst) plays an important role. As the organic products of these reactions were not yet identified experimentally, they were studied here by an HPLC technique. It was found that the main organic oxidation product of bromomalonic acid is bromo-ethene-tricarboxylic acid (BrEETRA), the same compound that is formed when bromomalonic acid is oxidized by Ce4+ (another catalyst of the BZ reaction). Formation of BrEETRA is explained here by a new mechanism that is more realistic than the one suggested earlier. To find any oxidation product of malonic acid in the ferriin-malonic acid reaction was not successful, however. Neither ethane-tetracarboxylic acid (ETA) nor malonyl malonate (MAMA), the usual products of the Ce4+- malonic acid reaction, nor any other organic acid, not even CO2, was found as a product of the reaction. We propose that malonic acid is not oxidized in the ferriin-malonic acid reaction, and it plays only the role of a complex forming catalyst in a process where Fe3+ oxidizes mostly its phenantroline ligand.