Solvent-free Mannich-type reaction as a strategy for synthesizing novel heterocalixarenes

Novel calix[2]imidazolidin[2]arenes were synthesized by solvent-free Mannich-type reaction, in quantitative yields, from 1,3-bis(2′-hydroxy-benzyl)imidazolidines and 1,3,6,8-tetraazatricyclo[4.4.1.1^3,8]dodecane (TATD).     

Synthesis of some new germasesquioxides by intramolecular catalytic Mannich-type reactions

A convenient procedure for the preparation of some new germasesquioxides containing phosphonyl groups carried by an intramolecular catalytic Mannich-type reaction is reported.     

Stereoselective synthesis of β-amino ketones via direct Mannich-type reaction catalyzed with silica sulfuric acid

At room temperature, the direct Mannich-type reaction of a variety of in situ generated aldimines using aldehydes and anilines with ketones in a three-component reaction was efficiently catalyzed by silica sulfuric acid (SSA) in EtOH. This rapid reaction afforded the corresponding β-amino ketones in good yields with excellent stereoselectivities and catalyst was recyclable.     

Catalyst-free Mannich-type reaction of 1-(N-acylamino)alkyltriphenylphosphonium salts with silyl enolates

A catalyst-free reaction of 1-(N-acylamino)alkyltriphenylphosphonium tetrafluoroborates with silyl enolates was developed to prepare β-amino carbonyl compounds. The reported method is a useful approach for the preparation of N-protected β-amino esters as well as N-protected β-amino ketones. The starting 1-(N-acylamino)alkyltriphenylphosphonium tetrafluoroborates are readily available from N-protected α-amino acids. Therefore, the presented approach can be considered a new method for the α-homologation of N-protected α-amino acids to prepare β-amino acid derivatives.     

Rapid alkenylation of quinoxalin-2(1H)-ones enabled by the sequential Mannich-type reaction and solar photocatalysis

Herein, a rapid alkenylation of quinoxalin-2(1H)-ones enabled by a combination of Mannich-type reaction and solar photocatalysis is demonstrated. A wide range of functional groups are compatible, affording the corresponding products in moderate-to-good yields. Control experiments illustrate that the in situ generated ¹O₂ plays a central role in this reaction. This green and efficient strategy provides a practical solution for the synthesis of potentially bioactive compounds that containing a 3,4-dihydroquinoxalin-2(1H)-one structure.     

One-pot carbon-carbon bond formation at the β-position of cyclic ketones: oxidative Michael addition with alkyl malonates

A carbon-carbon bond was formed at the β-position of cyclic ketones in a one-pot manner by oxidation with N-tert-butylbenzenesulfinimidoyl chloride, followed by the reaction of malonic acid esters or potassium cyanide.     

NbCl5-Catalyzed one-pot Mannich-type reaction: three component synthesis of β-amino carbonyl compounds

Three-component Mannich-type reaction of acetophenone, aromatic aldehydes and aromatic amines was catalyzed by NbCl₅ at ambient temperature to give various β-amino ketones in high yields.     

磺酰脲的类Mannich反应研究

研究了对甲苯磺酰脲与取代苯甲醛及亚磷酸二酯的类Mannich反应,用竞争反应的方法对不同胺组分发生类Mannich反应的活性进行了比较.合成了一系列α-对甲苯磺酰脲基磷酸二酯的化合物.产物的结构得到¹HNMR和元素分析的证明.初步生物活性测定结果表明其中某些化合物具有很好的抗烟草花叶病毒活性。     

Preparation of 2,2-disubstituted 1,2-dihydro-3H-indol-3-ones via oxidation of 2-substituted indoles and Mannich-type reaction

A novel preparative method for 2,2-disubstituted 1,2-dihydro-3H-indol-3-ones through the oxidation of 2-arylindoles followed by a Mannich-type reaction with carbon nucleophiles is described.     

N-alkylation of lactams with secondary heterobenzylic bromides

We herein report a general N-alkylation reaction of lactams with secondary heterobenzylic bromides. This methodology features mild reaction condition, moderate to high product isolation yield, and broad substrate scope. Good chemical and structural tolerance has also been demonstrated by both the secondary heterobenzylic bromides and lactam substrates.     

Enantioselective alkylation of lactams and lactones via lithium enolate formation using a chiral tetradentate lithium amide in the presence of lithium bromide

Enantioselective alkylation of lactams and lactones can be realized up to 98% ee by deprotonation with a chiral tetradentate lithium amide (4b) in the presence of lithium bromide, and subsequent alkylation with active alkylating agents in non-chelating solvents.     

Sulfated zirconia (SO4/ZrO2) as a reusable solid acid catalyst for the Mannich-type reaction between ketene silyl acetals and aldimines

Sulfated zirconia (SO₄/ZrO₂) catalyzed Mannich-type reactions of ketene silyl acetals and aldimines proceeded smoothly at room temperature to afford β-amino esters in good to high yields. In addition, the heterogeneous solid acid catalyst SO₄/ZrO₂ was easily recovered from the reaction mixture and then reused without significant loss of effectiveness.     

Asymmetric Mannich-type reactions catalyzed by indium(III) complexes in ionic liquids

In(III) complexes efficiently catalyse asymmetric Mannich-type reactions in ionic liquids with high diastereoselectivity and good yield.     

Lithium heptadecafluorooctanesulfonate catalyzed Mannich-type and aza-Diels-Alder reactions in supercritical carbon dioxide

The Mannich-type reaction of imines with (1-methoxy-2-methylpropenyloxy)trimethylsilane and aza-Diels-Alder reaction of imines with Danishefsky's diene can be carried out in scCO₂ in the presence of lithium heptadecafluorooctanesulfonate which offer a way to synthesize β-amino carbonyl compounds and nitrogen-containing six-membered ring compounds under environmentally benign conditions.     

Mechanistic studies on the catalytic asymmetric Mannich-type reaction with dihydroisoquinolines and development of oxidative Mannich-type reactions starting from tetrahydroisoquinolines

Detailed mechanistic studies on our recently reported asymmetric addition reactions of malonates to dihydroisoquinolines (DHIQs) catalyzed by chiral Pd(II) complexes were carried out. It was found that an N,O-acetal was generated in situ by the reaction of DHIQ with (Boc)2O, and cooperative action of the Pd(II) complex as an acid-base catalyst allowed the formation of a chiral Pd enolate and a reactive iminium ion via alpha-fragmentation. The iminium ion was also accessible via oxidation with DDQ as an oxidant, and a catalytic asymmetric oxidative Mannich-type reaction was achieved with tetrahydroisoquinolines (THIQs) as starting materials. This oxidation protocol was applicable to N-acryloyl-protected THIQs, allowing the efficient synthesis of optically active tetrahydrobenzo[a]quinolizidine derivatives via intramolecular Michael reaction.     

Novel acid-mediated reactions of phenyl-substituted lactams

Treatment of 3-phenylazetidin-2-one and 7-phenylazepin-2-one with triflic acid in benzene gave a novel, high yielding conversion to 3,3-diphenylpropionamide and 6,6-diphenylhexanoic acid amide, respectively. However, with AlCl₃, 7-phenylazepin-2-one was converted into 3-phenylazepin-2-one via a retro-Beckman rearrangement.     

The development of a Selectfluor®-mediated oxidative Mannich reaction

Selectfluor® is an easy to handle, air-stable and powerful electrophilic fluorination agent that can be used in a novel oxidative Mannich-type carbon-carbon bond forming process to allylate electron deficient tertiary amines in moderate to good yields. This process is rapid, operationally simple, insensitive to atmospheric conditions and of potentially broad use, especially in the construction of homoallylamines.     

Activation and stabilization of aldimines by an ortho-trifluoromethyl substituent in direct vinylogous Mannich-type reactions

Lewis acid catalyzed direct vinylogous Mannich-type reaction with a weak nucleophile dienol, generated in situ by ring-opening and rearrangement of vinyloxiranes, could be demonstrated in excellent yields under mild conditions using benzylidene(4-methoxy-2-trifluoromethyl)aniline (MTMA) as an electrophile. The o-trifluoromethyl substituent can stabilize imines by a steric effect and activate by an electron-withdrawing effect. It proved to be an easily deprotectable protecting group for direct Mannich-type reactions.     

Zirconium-catalysed N-acylation of lactams using unactivated carboxylic acids

A large number of chemicals including surfactants, nootropic drugs and pesticides contain an N-acylated lactam moiety in their molecular structure. In this work, the direct, catalytic N-acylation of a number of lactams with various unactivated carboxylic acids is reported. Several Lewis acid catalysts were evaluated for their activity in the N-acylation of pyroglutamic acid methyl ester with palmitic acid; the highest activities were observed for zirconium-based catalysts. Yields of up to 97% were obtained utilising 10?mol% Zr(propoxide)₄ in mesitylene at reflux temperature, but ZrOCl₂·8H₂O was determined as the most stable catalyst. The substrate scope was investigated and a number of lactam-carboxylic acid combinations were successfully converted into the desired products in 57–97% yield. This method provides an alternative synthetic pathway towards the drug aniracetam, which can be produced in 84% yield. A plausible catalytic mechanism is presented based on kinetic experiments.     

One-pot three-component tandem reaction: Synthesis of aryl/alkyl cyanamides libraries and their further conversion into tetrazole derivatives

We have developed methodology for the synthesis of aryl/alkyl cyanamides from amines in one-pot four steps reaction using cheap, readily available and air stable copper source as catalyst under mild reaction conditions. We have also studied the application of cyanamides. In this connection, we could construct aryl tetrazolamine from cyanamides using click reaction