Asymmetric dihydroxylation of heteroaromatic acrylates

N- and O-Heteroaromatic acrylates were dihydroxylated with high ees and good yields. While the AD of pyridyl and pyrryl acrylates afforded diverse yields under the present reaction condition, some corresponding N-substituted pyridyl and pyrryl acrylates (1d, 1e, 1g) proved to be appropriate substrates. The diols obtained can be used as chiral building blocks for the synthesis of various biologically active molecules.     

TfOH catalyzed synthesis of 1-substituted tetrahydrocarbazoles

Synthesis of 1-substituted tetrahydrocarbazole is accomplished by TfOH catalyzed reaction of 3-substituted indoles tethered with secondary and tertiary alcohols. The reaction was generalized for a variety of substrates and was extended to the synthesis of 2,3,3a,6-tetrahydro-1H-pyrido[3,2,1-jk]carbazole and carbazoles.     

Synthesis of meso-tetraphenyl porphyrins via condensation of dipyrromethanes with N-tosyl imines

A new synthetic route for the synthesis of 5,10,15,20-tetraphenyl porphyrins has been developed based on the reaction of 5-substituted dipyrromethanes with N-tosyl imines in the presence of a metal triflate catalyst. meso-Substituted tetraphenyl porphyrins were synthesized in a two-step process. The first step of the method is the metal triflate-catalyzed condensation of 5-substituted dipyrromethanes with N-tosyl imines to form a porphyrinogen intermediate and the second step is the oxidation of the porphyrinogen to porphyrin. The method was applied to the synthesis of trans-A₂B₂-tetraarylporphyrins and the products were obtained with only a trace amount of one scrambling product. The synthesis of two important building blocks for porphyrin synthesis, mono and di-sulfonamide alkylated 5-substituted dipyrromethanes, was achieved by the addition of 5-substituted dipyrromethane to N-tosyl imine. The application of mono and di-sulfonamide alkylated 5-substituted dipyrromethanes in ‘2+2’ porphyrin formation reactions is presented.     

l-Proline catalyzed domino Michael addition of N-substituted anilines

Here we report l-proline catalyzed 3-component reaction of indoles, aldehydes and N-substituted anilines in water as solvent at room temperature for the synthesis of 3-(α,α-diarylmethyl)indoles. The reaction is in fact a Michael addition of N-substituted anilines to alkylideneindolenines. The reaction is very clean, high yielding and having broad substrate scope. A tentative mechanism is proposed.     

Copper-catalyzed radical/radical cross-coupling of ketoxime carboxylates with 4-hydroxycoumarins: A novel synthesis of furo[3,2-c]-coumarins

A novel and efficient strategy for the synthesis of furo[3,2-c]coumarins has been developed via copper-catalyzed radical/radical cross-coupling of ketoxime carboxylates with 4-hydroxycoumarins. This redox-neutral reaction allows smooth and selective synthesis of 2-substituted, 3-substituted, 2,3-disubstituted and 2,3-fused polycyclic furo[3,2-c]coumarins.     

Rearrangement of oxazolidinethiones to thiazolidinediones or thiazinanediones and their application for the synthesis of chiral allylic ureas and α-methyl-β-amino acids

A novel rearrangement has been found between oxazolidinethiones and acyl halides under N-acylation reaction conditions to afford N-substituted 2,4-thiazolidinediones and N-substituted 1,3-thiazinane-2,4-diones. These heterocycles were used for the synthesis of chiral allylic ureas and α-methyl-β-amino acids.     

Facile synthesis of meso-substituted dipyrromethanes and porphyrins using cation exchange resins

The macroporosity and acidity of cation exchange resins play a crucial role in the synthesis of dipyrromethanes and porphyrins; for the first time, cation exchange resins have been used as heterogeneous solid acid catalysts to produce dipyrromethanes and porphyrins in good yields. The reaction, at room temperature, of substituted aromatic aldehydes with pyrrole catalysed by cation exchange resin afforded the corresponding meso-substituted dipyrromethane in yields ranging from 70 to 80%, indicating the broad scope of the reaction. Further, the condensation of meso-substituted dipyrromethane with similar or different substituted aromatic aldehydes, using cation exchange resins furnished meso-tetrakis-symmetrical and mixed porphyrins, respectively. One-pot synthesis of porphyrins can also be carried out directly from the aldehydes and pyrrole under the above conditions. Acidolysis of the dipyrromethane is negligible under the conditions of the porphyrin-forming reaction.     

One-step construction of carbazoles by way of the palladium-catalyzed double N-arylation reaction and its application to the total synthesis of murrastifoline-A

The one-step construction of N-substituted carbazoles by way of the Pd-catalyzed double N-arylation reaction of primary amines with 2,2′-dibromobiphenyl is described. Aryl and aliphatic amines including tert-butylamine and a protected glucopyranosylamine were effectively transformed into the corresponding N-substituted carbazoles. The first total synthesis of murrastifoline-A, a biscarbazole alkaloid, based on this methodology is also presented.     

Formal total synthesis of (+)-wortmannin using catalytic asymmetric intramolecular aldol condensation reaction

A catalytic process for the synthesis of optically active C4-substituted tetrahydroindandiones using an asymmetric intramolecular aldol condensation reaction was developed. When 30 mol% of phenylalanine and 50 mol% of pyridinium p-toluenesulfonate were used under highly concentrated conditions, a variety of C4-substituted tetrahydroindandiones and octahydronaphthalenediones were obtained in high yield (up to 89% yield) and high enantiomeric excess (up to 94% ee). One of the products was successfully transformed into the key intermediate for the synthesis of the phosphatidylinositol 3-kinase inhibitor wortmannin, achieving formal total synthesis of (+)-wortmannin.     

Reaction of N-Fmoc aspartic anhydride with glycosylamines: a simple entry to N-glycosyl asparagines

The reaction of N-Fmoc-aspartic anhydride with glycosyl amines in DMSO selectively leads to the formation of β-substituted products, thus providing a simple and efficient route to N-glycosyl asparagine derivatives, the building blocks for glycopeptide synthesis.     

A new reagent for the synthesis of [26]hexaphyrin: N-sulfonyl aldimine

The selective synthesis of [26]hexaphyrin(1.1.1.1.1.1) has been achieved by the reaction of meso-substituted tripyrrane and N-sulfonyl aldimine. The protocol is simple and requires only a catalytic amount of copper(II) triflate under mild reaction conditions.     

Studies on Cu(I)-catalyzed synthesis of simple 3-substituted 1,2-allenes and optically active 2-substituted secondary 2,3-allenols

The sequential treatment of terminal alkynes or propargylic alcohols with n-BuLi and MOMCl afforded the corresponding propargylic methyl ethers, which would react with primary alkyl Grignard reagents under the catalysis of CuBr to afford 3-substituted 1,2-allenes or 2-substituted secondary 2,3-allenols, respectively. The reaction may be applied to the synthesis of optically active 2-substituted secondary 2,3-allenols with up to >99% ee without any protection to the free hydroxyl group in the starting 4-hydroxy-2-alkynyl methyl ethers.     

Silica triflate as an efficient reagent for the solvent-free synthesis of coumarins

Silica triflate,as a new silica-based reagent,can be used for the efficient synthesis of 4-substituted coumarins via a Pechmann reaction under solvent-free reaction conditions.All reactions were performed at 80℃in good to high yields.     

Synthesis of 1,1-diarylethylenes from an α-stannyl β-silylstyrene

The synthesis of a family of 1,1-diarylethylenes from an α-stannyl β-silylstyrene through a combination of a Stille coupling and a protodesilylation reaction is described. This approach avoids the problematic cine-substitution, which is a well documented side reaction during the palladium-assisted elaboration of α-substituted vinylstannanes to 1,1-disubstituted ethylenes.     

One-pot three-component coupling reaction: solvent-free synthesis of novel 3-substituted indoles catalyzed by PMA-SiO2

Solvent-free PMA-SiO₂-catalyzed synthesis of 3-substituted indole derivatives by a one-pot three-component coupling reaction between aldehyde, N-methyl aniline and indole is described.     

Copper-catalyzed tandem intramolecular cyclization/coupling reaction: solvent effect on reaction pathway

In this study, we developed direct methods for the synthesis of 3-substituted indoles from o-alkynylanilines by utilizing a copper-catalyzed tandem intramolecular cyclization/coupling reaction under mild and simple reaction conditions. Our investigation revealed that choice of the aprotic polar solvents and additives such as camphorsulfonic acid is critical in this reaction.     

Diastereoselective synthesis of novel 5-substituted morpholine-3-phosphonic acids: further exploitation of N-acyliminium intermediates

The first diastereoselective total synthesis of 5-substituted morpholine-3-phosphonic acids is reported. The principal feature of the synthesis is the introduction of a dimethyl phosphonate group into 5-substituted morpholin-3-ones. The procedure is based on the preparation of N-Boc-(S)-5-phenyl- and N-Boc-(S)-5-benzylmorpholin-3-one from l-phenylglycine and l-phenylalanine methyl esters, followed by the formation of the 3-methoxylated compounds and subsequent reaction with trimethyl phosphite in the presence of BF₃·OEt₂. Diastereoselectivity in the formation of cis-disubstituted products is in agreement with the nucleophilic addition to other methoxylated derivatives.     

Synthesis of 2-substituted indoles by iridium (III)-catalyzed CH functionalization of N-phenylpyridin-2-amines

A highly regioselective synthesis of 2-substituted indoles was realized through Ir(III)-catalyzed CH functionalization of N-phenylpyridin-2-amines followed by the reaction with sulfoxonium ylides and intramolecular cyclization under mild conditions. The reaction completed with broad range of substrate scopes and gave various 2-substituted indoles in up to 98% yields.     

Direct [3+2]-cycloaddition of electron-deficient alkynes with CF3CHN2: Regioselective one-pot synthesis of 3-trifluoromethylpyrazoles

A direct and facile cycloaddition reaction of electron-deficient terminal alkynes with 2,2,2-trifluorodiazoethane under mild conditions to afford a series of 5-substituted 3-trifluoromethylpyrazoles in high yields is described. The potential application of this cycloaddition reaction was demonstrated via the efficient synthesis of a key intermediate of the antiviral drug AS-136A and a fluorinated analog of Tebufenpyrad.     

A new approach to the synthesis of 3,4-dihydroisocoumarin derivatives

A new, simple, one-step synthesis of 3-substituted 3,4-dihydroisocoumarins is developed. The products are obtained by the reaction of o-methoxycarbonyl arenediazonium bromides with unsaturated compounds in the presence of CuBr as a catalyst.