Facile and highly diastereoselective synthesis of 3-aminooxindoles via AgOAc-catalyzed vinylogous Mannich reaction

A novel AgOAc-catalyzed vinylogous Mannich reaction between easily prepared imines 1 derived from isatins and trimethylsilyloxyfuran 2 (TMSOF) was developed. This method provided a facile synthetic route to get access to synthetically useful quaternary 3-aminooxindole in excellent yields (94–99%) and diastereoselectivities (>99:1).     

Highly diastereoselective switchable enantioselective Mannich reaction of glycine derivatives with imines

Tuning of diastereoselectivity was realized in the Mannich reaction of glycine derivatives with aromatic and aliphatic N-Ts imines using CuClO4-FcPHOX ligand 4b and 4f having an MeO group at the 4-position and F atom at the 3,5-position of the phenyl ring on the P-atom respectively as catalyst, providing either anti- or syn-alpha,beta-diamino acid derivatives in high yields and in high diastereo- and enantioselectivities.     

A catalytic metal-free Ritter reaction to 3-substituted 3-aminooxindoles

The first Ritter reaction of 3-substituted 3-hydroxyoxindoles with nitriles, catalyzed by HClO(4), is developed, which enables the synthesis of 3-substituted 3-aminooxindoles in good to excellent yield with rich diversity.     

Highly diastereoselective asymmetric Mannich reactions of 1,3-dicarbonyls with acyl imines

[reaction: see text] The cinchona alkaloids catalyze direct asymmetric Mannich reactions of cyclic 1,3-dicarbonyl compounds with acyl imines to afford alpha-quaternary carbon-bearing reaction products in yields of up to 98%, a diastereomeric excess of 90% or greater, and enantioselectivities up to 99% ee. A model is proposed that accounts for both the observed diastereoselectivities and the enantioselectivities for the reactions.     

A convenient route to enantiopure 3-aryl-2,3-diaminopropanoic acids by diastereoselective Mannich reaction of camphor-based tricyclic iminolactone with imines

A novel and convenient route to the asymmetric synthesis of 2,3-diamino acids via Mannich reaction of iminolactones 1a and 1b with N-protected imines has been achieved in good yields (up to 95%) and high diastereoselectivity (dr: >99:1). Hydrolysis of the Mannich adducts under acidic conditions furnished the desired 3-aryl-2,3-diaminopropanoic acids in good yields (up to 85%) with excellent enantiomeric excesses (99% ee).     

Asymmetric synthesis of 3-amino-2-hydroxyalkanoates by Mannich reaction of menthyl acetate with imines and subsequent oxidation

Lithium amide-assisted Mannich-type reaction of menthyl acetate-derived lithium enolate with PMP-arylaldimines and subsequent in situ oxidation with oxaziridine gave syn-3-amino-3-aryl-2-hydroxypropanoates with high syn-selectivity and diastereoselectivity (with respect to menthyl moiety) in a one-pot procedure. Propargyl aldehyde-derived imines were also stereoselectively converted to the Mannich-oxidation products by a stepwise procedure.     

Enantioselective direct Mannich reaction of functionalized acetonitrile to N-Boc imines catalyzed by quaternary phosphonium catalysis

Quaternary phosphonium ion-pair or a salt derived from amino acid has been developed to catalyze the Mannich-type reaction of α-substituted ethyl cyanoacetates and 2-(2-nitrophenyl) acetonitrile to N-Boc imines. Experiments shown that more active cyanoacetates could be catalyzed by the gentle phosphonium ion-pair catalysis, while 2-(2-nitrophenyl) acetonitrile as the substrate has to be activated by quaternary phosphonium salts and strong base. All the reactions gave the corresponding highly functionalized chiral β-amino nitriles products with good yields, high diastereo- and enantioselectivities in mild conditions.     

金催化肌酸酐与靛红的加成反应:一种可持续的绿色方法用于非对映选择合成3-取代的3-羟基靛红

报道了水介质中金催化肌酸酐与不同靛红之间的醛醇缩合反应.该法无需繁杂的溶剂萃取和柱色谱技术,只需简单的过滤即可将产物分离出来,因而操作简单.通过较宽范围的靛红衍生物的反应,均可高产率并完全地制取相应的顺式醛醇缩合产物,因此该法表现出较高的通用性.还将该合成策略进一步拓展至靛红,肌酸酐和丙二腈的串联反应,可高产率、完全的制取反式多组分产物.采用分光光度法测定了合成产物的抗氧化性能,结果表明,与标准物相比,含有卤素原子的三个化合物(2c,2d和2e)表现出最高的活性.     

Aqueous single step synthesis and structural characterization of allylated,propargylated, and benzylated 3-substituted 3-aminooxindoles

Efficient zinc-mediated allylation, propargylation, and benzylation of isatin-derived imines were undertaken for the synthesis of 3-substituted 3-aminooxindoles with ≈80% yield. Such alternative approach has efficiently avoided the use of catalysts, severe reaction conditions, multistep procedures, and reaction additives. For exploring and materializing the synthetic utility, different allyl, propargyl, and benzyl bromides were used for generalizing the synthetic route. The structure of the synthesized compounds was established and confirmed by ¹H NMR, ¹³C NMR, FTIR, and mass spectroscopic techniques.     

Diastereoselective vinylogous Mannich reaction of perfluoroalkylated cyclic imines with 2-trimethylsilyloxyfuran

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The Mannich reaction of malonates with simple imines catalyzed by bifunctional cinchona alkaloids: enantioselective synthesis of beta-amino acids

We describe the first efficient, direct asymmetric Mannich reactions with malonates and N-Boc aryl and alkyl imines by cooperative hydrogen-bonding catalysis with a cinchona alkaloid bearing a thiourea functionality. We have also extended the scope of this reaction to beta-ketoesters. The synthetic value of this new reaction is demonstrated in the establishment of a convergent enantioselective route toward the biologically important beta-amino acids under mild and air- and moisture-tolerant conditions.     

Enantioselective synthesis of (+)-α-vetivone through the Michael reaction of chiral imines

(+)-α-Vetivone has been synthesised in nine steps. The absolute stereochemistry of the two stereogenic centres is controlled in the same key step involving the stereoselective Michael addition of a chiral imine of 4-isopropylidene-2-methylcyclohexanone to phenyl crotonate.     

Enantioselective synthesis of (3-indolyl)glycine derivatives via asymmetric Friedel-Crafts reaction between indoles and glyoxylate imines

Chiral phosphoric acid-catalyzed enantioselective Friedel-Crafts reaction of indoles with ethyl glyoxylate imines was developed. With 10 mol % of the catalyst, the Friedel-Crafts reactions between a wide range of indoles and imines have been carried out, affording optically active (3-indolyl)glycine derivatives with excellent yields and high enantioselectivities (up to 87% ee).     

Enantioselective direct Mannich reactions of 3-substituted oxindoles catalyzed by chiral phosphine via dual-reagent catalysis

A combination of an amino acid-derived chiral phosphine catalyst and methyl acrylate to catalyze the direct Mannich reaction of 3-substituted oxindoles and imines has been reported to afford 3-tetrasubstituted oxindole derivatives which are key structures for biological activities. The products are formed with a quaternary carbon and featured with two adjacent chiral centers. Various N-EDG(electron-donating group) and N-EWG(electron-withdrawing group) protected oxindoles, including 3-aryl and 3-alkyl substituted ones, have been evaluated with aromatic and aliphatic imines under this catalytic system, smoothly giving desired products in good yields as well as excellent diastereo- and enantioselectivities.     

Enantioselective synthesis of 2-substituted cyclobutanones

[formula: see text] An enantioselective synthesis of 2-substituted cyclobutanones has been achieved by sequential application of the titanium-mediated cyclopropanation of alpha-hydroxy esters and the pinacol-type rearrangement of the resulting alpha-hydroxycyclopropylcarbinols.     

Facile and general synthesis of quaternary 3-aminooxindoles

A novel approach to the valuable quaternary 3-aminooxindole skeleton is reported on the basis of intramolecular arylation of enolates of substituted amino acids. The reaction tolerates dialkyl- and arylalkylamines as well as a range of carbon substituents (primary and secondary alkyl, aryl). The cyclization of N-indolyl-substituted substrates is accompanied by direct C-H arylation of the indole, leading to indolo-fused benzodiazepines.     

A new synthesis of pyrrolidines by way of an enantioselective Mannich/diastereoselective hydroamination reaction sequence

A new two-step synthesis of highly substituted pyrrolidines has been developed. Chiral silane Lewis acid promoted enantioselective Mannich reactions of silyl ketene imines with acylhydrazones may be used to access bishomoallylic benzoic hydrazides that in turn may be cyclized to pyrrolidines by way of the thermal hydroamination reaction reported recently by Beauchemin. Importantly, excellent diastereoselectivity may be realized in the hydroamination reactions.     

Enantioselective synthesis of imidazolines with quaternary stereocenters by organocatalytic reaction of N-(heteroarenesulfonyl)imines with isocyanoacetates

An organocatalytic enantioselective Mannich-type reaction of isocyanoacetate with N-sulfonylimines catalyzed by chiral thioureas derived from quinine yielded 2-imidazolines with high diastereo- and enantioselectivities (up to >99:1 dr. and 96% ee). This reaction provided a convenient route to access various imidazolines and related α,β-diamino acids having a quaternary carbon center in high enantiomeric purities.