13505-39-0

A series of substituted 2-amino-1,3-thiazines were synthesized as amides (9a–9i), carbamates (9j–9m), sulfonamides (9n–9o) and urea derivatives (9p–9q) by treating the compound 7 with acid chlorides (8a–8i), chloroformates (8j–8m), sulfonyl chlorides (8n–8o) and isocyanates (8p–8q) respectively. The synthesized compounds (9a–9q) were screened for antituberculosis activity against Mycobacterium tuberculosis H37Rv ATCC 27294 and the results show that some of these derivatives possess good activity against Mycobacterium tuberculosis H37Rv ATCC 27294. A few also display promising cytotoxic activity against human breast cancer MCF-7 and human esophageal cancer EC-9706 cell lines. Regarding both biological profiles 9b, 9m and 9h are the most active for anti-cancer, anti-TB activity.

Rationally designed tetrahydropyrans (THPs) carrying one, two, or three aryl rings and other substituents were synthesized by the allylation of β-hydroxy ketones followed by iodocyclization. It has been observed that compounds with one aryl ring on THP ar

Boron-catalyzed environmentally benign dehydrative Friedel-Crafts alkylation of indole/pyrrole and aniline derivatives with β-hydroxyl ketones has been developed for the first time. This method provides an efficient and green replacement of toxic and unst

We developed a simple and environmentally benign visible-light-driven dehydrogenation of benzylic alcohols to the corresponding aldehydes or ketones. By using the dual catalyst system consisting of eosin Y as a photocatalyst and a Ni(ii) complex as a proton reduction catalyst, we could dehydrogenate benzylic alcohols to aldehydes or ketones with excellent yields under mild conditions. The sole byproduct is hydrogen gas.

The hydration of α,β-unsaturated ketones with water proceeded efficiently in the presence of In(OTf)3 (20 mol%) in aqueous media to afford synthetically versatile β-hydroxyketones in moderate to good yields with good functional group compatibility. The method also can be extended to the hydroalkoxylation of α,β-unsaturated ketones with various alcohols for the efficient synthesis of β-alkoxyketones as well as tetrahydrofuran derivatives. (Figure presented.).

An efficient chromium(III) chloride-catalyzed Michael-type reaction of water or alcohol with α,β-unsaturated ketones is developed. A variety of α,β-unsaturated ketones effectively reacted with either water or alcohols to give the corresponding β-hydroxyl ketones or β-alkoxyl ketones in modest to high yields with excellent compatibility to various functional groups. The approach was further utilized for the preparation of synthetically useful compounds containing tetrahydrofuran skeleton.

The invention provides a synthesis method for a beta-hydroxy-ketone compound shown in a formula (III). The method comprises the steps that substitute vinyl acetate shown in a formula (I), a substitute alcohol compound shown in a formula (II) and an oxidizing agent are mixed to obtain reaction liquid, and the reaction liquid reacts for 2-12 hours at the temperature of 20 DEG C-120 DEG C, and then is treated to obtain the beta-hydroxy-ketone compound. The method is safe and environmentally friendly, and is a new path for synthesizing the beta-hydroxy-ketone compound containing various substituents, the substrate adaptability is good, and the reaction operation is easy.

The invention discloses a method for preparing an organoboron compound under a catalytic effect of chitosan immobilized copper and an application. The method comprises the following steps: A) adding a chitosan immobilized copper catalyst and a ligand into a reaction tube and stirring; B) respectively continuously adding an initial raw material I and bisdiboron into a system in turn; C) stirring the whole reaction system and reacting under room temperature; D) after the reaction is ended, filtering the whole reaction system, washing with tetrahydrofuran, performing rotary evaporation and concentration on a filtrate, adopting a mixed solvent of ethyl acetate and petroleum ether at different ratios for performing column chromatography on the residues, separating and purifying, thereby acquiring a target product II. The silica gel is taken as a fixing phase for column chromatography. The invention also relates to the application of the prepared organoboron compound in compounding beta-hydroxy compound and anti-cancer drug molecules. The method is feasible; the operation is simple and convenient; the method is suitable for various substrates and can be used for successfully preparing the corresponding target compounds. The catalyst is low in dosage and is recyclable, is easily separated after the ending of the reaction, is free from metal residue and is suitable for large-scale production.

Selective oxidation of alcohols to aldehydes/ketones has been achieved with the help of 3-mercaptopropionic acid (MPA)-capped CdSe quantum dot (MPA-CdSe QD) and visible light. Visible-light-prompted electron-transfer reaction initiates the oxidation. The thiyl radical generated from the thiolate anion adsorbed on a CdSe QD plays a key role by abstracting the hydrogen atom from the C?H bond of the alcohol (R1CH(OH)R2). The reaction shows high efficiency, good functional group tolerance, and high site-selectivity in polyhydroxy compounds. The generality and selectivity reported here offer a new opportunity for further applications of QDs in organic transformations.

We herein report a green and recyclable chitosan supported copper catalyst which is capable of catalyzing the borylation of α,β-unsaturated acceptors in water at room temperature. A broad substrate scope including chalcone derivatives, esters and nitriles have been explored. In all the cases, desired products were obtained in good to excellent yields. Remarkably, this chitosan supported catalyst could be recovered and reused for five times without any significant decrease of reactivity.

A metal-free TBHP-mediated radical alkylation of enol acetates with alcohols is described. This method provides a new route to a variety of β-hydroxy-ketones in moderate to good yields.

A highly chemoselective visible light mediated strategy has been developed for oxidation of benzylic alcohols. The method circumvents the use of toxic metal catalysts, high energy light source, and operates at room temperature. Furthermore reaction is easily scalable to gram levels.

Regio- and stereo-selective reduction of substituted 1,3-aryldiketones, investigated in the presence of different whole cell microorganisms, was found to afford β-hydroxyketones or 1,3-diols in very good yields (up to 95%) and enantiomeric excesses (up to 96%). The enantiomerically enriched aldols, obtained with the opposite stereo-preference by baker's yeast and Lactobacillus reuteri DSM 20016 bioreduction, could then be diastereoselectively transformed into optically active syn- or anti-1,3-diols by a careful choice of the chemical reducing agent (diastereomeric ratio up to 98 : 2). The latter, in turn, were stereospecifically cyclized into the corresponding oxetanes in 43-98% yields and in up to 94% ee, thereby giving a diverse selection of stereo-defined 2,4-disubstituted aryloxetanes.

A zerovalent copper- and cobalt-catalyzed direct coupling of the sp3 α-carbon of alcohols with alkenes and hydroperoxides was developed in which the hydroperoxides acted as radical initiator and then coupling partner. 1,3-Enynes and vinylarenes

A simple but efficient organocatalytic system with 5 mol% tetra-n-butylammonium bromide (TBAB) as the catalyst has been identified for alcohol oxidation for the first time. This organocatalytic system is compatible with a broad range of benzylic/allylic alcohols with various catalytically reactive groups. Besides, it shows excellent selectivity for secondary benzylic alcohols over aliphatic alcohols, and good selectivity over the primary benzylic alcohol site in 4-(1-hydroxyethyl)benzyl alcohol. Thus, the features of simplicity, high efficiency, selectivity and mildness of reaction conditions associated with this TBAB organocatalytic system suggest its potential for widespread use in synthetic chemistry.

Fourteen chiral α- and β-keto alcohols 2a-2r were synthesized by the asymmetric reduction of their corresponding diketones 1a-1r via baker's yeast. In addition, ten corresponding racemic α-keto alcohols were synthesized by the benzoin condensation of their corresponding aldehydes, which were used for the determination of the ee values through their chiral resolution on chiral HPLC. Amongst the 15 diketones, 1j and chiral α-keto alcohols 2i, 2j and chiral β-keto alcohol 2r are novel compounds. Six keto alcohols 2b, 2c, 2d, 2f, 2h and 2p were synthesized by baker's yeast for the first time. There are some studies in the literature where baker's yeast was applied to the diketones 1a, 1g, 1e, 1k and 1n under various conditions different to those reported herein. The yields and the ee values of these studies were not as high as ours. All of the keto alcohols synthesized were characterized by IR, NMR (1H and 13C), and MS. The relationship between the structure of the diketone and the yield, diastereoselectivity and enantiomeric excess is also discussed.

Enantioenriched potassium β-trifluoroboratoamides have been synthesized via an asymmetric, copper-catalyzed 1,4-addition of tetrahydroxydiboron (BBA) and tetrakis(dimethylamino)-diboron to α,β-Unsaturated amides. These dibora reagents provide access to the desired organotri-fluoroborates using effective and atom economical sources of boron. The copper-catalyzed β-boration is extended to α,β- Unsaturated ketones and esters. The desired potassium organotrifluoroborates are synthesized with yields up to 92% and enantiomeric ratios up to 98:2. The enantioenriched potassium btrifluoroboratoamides are successfully cross-coupled with an array of aryl and heteroaryl chlorides in high yield with complete stereochemical fidelity as the transmetalation proceeds through an SE2 mechanism via an open transition state.

The twisted 3,3′-diiodo-2,2′,6,6′-tetramethoxybiphenyl-4, 4′-dicarboxylic acid (DIDA) was designed and synthesized for the in situ generation of Bis-IBX and catalytic oxidations. The seemingly better solubility of the in situ-generated Bis-IBX and the attenuated reactivity arising from its unique structural features and methoxy substituents allowed the catalytic oxidation of activated alcohols selectively using DIDA/oxone. Chemoselective oxidations were demonstrated for substrates containing two different hydroxy groups. Furthermore, the unique reactivity of DIDA was demonstrated for sequential oxidation reactions of 1,4- and 1,6-diols to give lactones catalytically in respectable yields.

Catalytic Pd(OAc)2 and polymethylhydrosiloxane (PMHS), in conjunction with aqueous KF, and a catalytic amount of an aromatic chloride, effects the chemo-, regio-, and stereoselective deoxygenation of benzylic oxygenated substrates at room temperature in THF. Preliminary mechanistic experiments suggest the process to involve palladium-nanoparticle-catalyzed hydrosilylation followed by C-O reduction. The chloroarene additive appears to facilitate the hydrogenolysis process through the slow controlled release of HCl.

The reduction of 1,3-diketones and β-hydroxyketones with NaBH 4 in aqueous acetonitrile is highly stereoselective in the presence of stoichiometric amounts of bovine or human albumin, giving anti 1,3-diols with d.e. up to 96%. The same reaction, without albumin, gives syn and anti 1,3-diols in approximately 1:1 ratio. The presence of an aromatic carbonyl group is essential for diastereoselectivity in the NaBH4/albumin reduction of both 1,3-diketones and β-hydroxyketones. Thus, 3-hydroxy-1-(p-tolyl)-1- butanone is stereoselectively reduced in the presence of albumin, while reduction of its isomer 4-(p-tolyl)-4-hydroxy-2-butanone is not stereoselective. The albumin-controlled reduction is not stereospecific as both enantiomers of 1-aryl-3-hydroxy-1-butanones are reduced to diols with identical stereoselectivities. Circular dichroism of the bound substrates confirms that aromatic ketones are recognized by the protein's IIA binding site. Binding studies also suggest that 1,3-diketones are recognized in their enol form. From the effect of pH on binding of a diketone it is concluded that, in the complex with the substrate, ionizable residues His242 and Lys199 are in the neutral and protonated forms, respectively. A homology model of BSA was obtained and docking of model substrates confirms the preference of the protein for aromatic ketones. Modelling of the complexes with the substrates also allows us to propose a mechanism for the reduction of 1,3-diketones in which the chemoselective reduction of the first (aliphatic) carbonyl is followed by the diastereoselective reduction of the second (aromatic) carbonyl. The role of albumin is thus a combination of chemo- and stereocontrol.

The synthesis of polymer-supported 2-monosubstituted 1,3-dithianes from soluble copolymers bearing 1,3-propanedithiol groups, their lithiation, reactions with electrophiles such as aldehydes, ketones, α,β- unsaturated ketones and oxiranes, and cleavage of

The total syntheses of diospongins A and B employing 2,6-disubstituted dihydropyranones as key intermediates are described.

(Chemical Equation Presented) Reduction of a series of β- hydroxyketones by Sml2/H2O/Et3N provided 1,3-diols in quantitative yields. The reactions were exceedingly clean with no byproduct formation, negating the need for f

Benzeneseleninic anhydride in the presence of tert-butyl hydroperoxide in chlorobenzene at about 70°C is an effective oxidizing agent for the selective oxidation of alcohols at the benzylic position.

Enzymes play an important role in guiding the diastereoselectivity of the final products during the chemical reduction of the intermediates (R)- and (S)-3-hydroxy-1-phenyl-1-butanone, prepared by bioreduction of 1-phenyl-1,3-butadione. For example, the pr

The reductions of a series of β-hydroxyketones by Sml2 were examined in THF, DME, and CH3CN using methanol as a proton source. Reductions in THF and DME typically lead to the syn diastereomer with DME providing higher diastereoselect

An unprecedented combination of high chemo- and stereoselectivity in the NaBH4 reduction of 1:1 complexes between albumin and aromatic 1,3-diketones results in the formation of anti 1,3-diols with de up to 96%.

Irradiation (λ >300 nm) of Hantzsch 1,4-dihydropyridine with aromatic α,β-epoxyketones in acetonitrile selectively breaks the Cα-O bond of the epoxides giving the corresponding β-hydroxyketones in excellent yields.

Scandium trifluoromethanesulfonate is a useful Lewis acid catalyst for cleavage of acetates containing coordinative groups adjacent to the acetyl carbonyl. The reaction proceeds under weak acidic conditions at room temperature. Racemizable α-keto acyloxy compounds are deacetylated without racemization. Selective mono-deacetylation at the 10-position of paclitaxel has been achieved.

Scandium trifluoromethanesulfonate is found to be a Lewis acid catalyst for selective cleavage of esters containing a coordinative group adjacent to an ester moiety. The reaction proceeds under weak acidic conditions at room temperature; the catalyst can be recovered and reused. Even α-acyloxy ketones are deacetylated without racemization. Selective monodeacetylation at C-10 of paclitaxel has been achieved.

The reactions of aldehydes and their O-acylated derivatives (α-chloroesters, acylals) with olefins and α-ethoxystyrene in the presence of SnCl4 and ZnCl2 were investigated. The reactions afforded various bifunctional derivatives: diols, hydroxyesters, chloroesters, 1,3-ketoalcohols.

Three types of highly coordinated organotin hydrides, Bu2SnIH-Lewis base (Lewis bases; HMPA or tripiperidinophosphine oxide) (type A), Bu2SnFH-HMPA (type B), and Bu3SnH-Bu4NX (X = F, CN) (type C), were characterized as nucleophilic, chelation, and nonchelation types of reductants, respectively, in the reaction with 2,3-epoxy ketones 1. These reagents, which promoted a reduction of the epoxy ring and syn-selective and anti-selective carbonyl reduction, respectively, were spectroscopically confirmed with 1H, 13C, 19F, and 119Sn NMR and FT-IR. Furthermore, the correlations between their structures and selective reducing abilities were discussed.

A novel reagent, Bu3SnH/Bu3SnI-phosphine oxide, reduced functionalized epoxides to the corresponding alcohols in high chemo- and regioselectivities.

An efficient access to chiral, non racemic arylbutanols 1a-c (ee > 98%) as drug intermediates is described. Thioacetalization of substituted benzaldehydes 3a-c with 1,3-propanedithiol gave 2-aryl-1,3-dithianes 4a-c. Lithiation of 4a-c followed by reaction with racemic, (R)- or (S)-propylene oxide, respectively, gave racemic, (R)- or (S)-hydroxyalkyldithianes 5a-c in high yields. Subsequent desulfurization with tributyltin hydride (TBTH) resulted in almost quantitative formation of the arylbutanols 1a-c. Ketols 6 were obtained by hydrolysis of the hydroxyalkyldithianes 5a.

Reactive aldehydes such as formaldehyde and α-chloro aldehydes can be successfully generated by treatment of readily available trioxane and α-chloro aldehyde trimers, respectively, with methylaluminum bis(2,6-diphenylphenoxide) (MAPH), and stabilized as their 1:1 coordination complexes with MAPH. The resulting CH2=O·MAPH complex reacts with a variety of olefins to furnish ene-reaction products with excellent regio- and stereoselectivities. In addition, this complex as well as α-chloro aldehyde-M APH complexes can be utilized as a stable source of gaseous formaldehyde and reactive α-chloro aldehydes, respectively, for the nucleophilic addition of various carbanions (organometallics, enolates, etc.). Formation of reactive aldehyde-MAPH complexes is firmly confirmed by 1H NMR spectroscopy. A space-filling model of aldehyde-M APH complexes implies that formaldehyde and α-chloro aldehydes coordinated with MAPH may be electronically stabilized by two parallel phenyl groups of aluminum ligands.

A systematic study of the regio- and diastereoselectivity of the kinetic Michael addition of amide and thioamide enolates to a series of α,β-unsaturated ketones has been carried out.Factors that influence the diastereo- and regiochemical outcome of the reaction include the substitution pattern of the enone and enolate, the enolate counterion, and the solvent.Numerous examples of high selectivity have been discovered.In a number of examples, either the syn or the anti addition products can be obtained by varying the nature of the solvent, donor atom, and/or counterion.These results have correlated in terms of a coherent transition-state model.

Barium permanganate is used for the efficient oxidation of different types of alcohols and acyloins to the corresponding carbonyl compounds in boiling acetonitrile.The mildness of this reagent is shown by the oxidative S,S-coupling of several thiols to disulfides.

Group IVA metallocene complexes such as bis(η5-cyclopentadienyl)zirconium dihydrides, Cp2ZrH2 (1), and hafnium dihydrides, Cp2HfH2 (8), catalyze the chemoselective reduction of polycarbonyl compounds to hydroxy carbonyl compounds.For instance, the reduction of keto aldehydes 3-ketobutanal (2g) and 2-phenyl-2-ketoethanal (2h) proceeded selectively at aldehyde group to provide the corresponding hydroxy ketones 3g and 3h in 91percent and 93percent yields, respectively.Under similar conditions, however, cyclohexanediones were easily aromatized to benzenediols.On the other hand, 1 and 8 also catalyze the selective 1,2-reduction of various types of α,β-unsaturated carbonyl compounds, giving the corresponding allylic alcohols in good to excellent yields.Thus, steroidal dicarbonyl compounds, having an enone framework in their molecules Δ4-androstene-3,17-dione (11a) and Δ4-progestene-3,20-dione (11b) were reduced by 1 to 17-hydroxy-Δ4-androsten-3-one (12a) and 20-hydroxy-Δ4-progest-3-one (12b), which are essential human hormones, in 80percent and 67percent yields, respectively.

Reaction of α-halogeno ketones with aldehydes in the presence of CeI3 in tetrahydrofuran is found to give α,β-unsaturated ketones in excellent yields under mild conditions.In contrast, treatment of α-halogeno ketones and carbonyl compounds with CeCl3-NaI or CeCl3-SnCl2 affords β-hydroxy ketones in good yields.It is assumed that these reactions proceed via cerium enolates.The combined reagents, however, cannot be applied to a Reformatsky-type reaction.Regiospecific and aldehyde chemoselective aldol synthesis are also described.

Bakers' yeast reduces 1-phenyl-1,3-butanedione with high chemo- and enantio-selectivity to give (S)-(+)-3-hydroxy-1-phenyl-1-butanone.The enantiomeric purity (>98percent)was determined by nmr analysis using a chiral shift reagent and the absolute configur

Selective double bond reduction of unsaturated conjugated ketones has been achieved in excellent yields by use of sodium dithionite in a two phase benzene-water system with Adogen as phase transfer catalyst.However, this reduction was unsatisfactory for hydrophilic ketones; in this case, competitive reactions led to the predominant formation of water soluble sulfur derivatives, similar to those obtained in the reaction of unsaturated conjugated ketones with sodium dithionite in aqueous dimethylformamide.

The preparation of bis(2,2'-bipyridyl)copper(II) permanganate (BBCP) is described.The reagent converts alcohols to the corresponding carbonyl compounds, α-hydroxy ketones to diketones, hydroquinone to p-benzoquinone, and compounds with benzylic double bonds to benzaldehyde in high yield.Benzophenone oxime, acetophenone oxime and various benzaldoximes are converted to the corresponding carbonyl compounds, aromatic amines to azo compounds, and benzylamine to benzaldehyde, usually in high yields, under mild condition.