Elemental Sulfur-Mediated Aromatic Halogenation.

A method for aromatic halogenation using a combination of elemental sulfur (S) and -halosuccinimide has been developed. A catalytic quantity of elemental sulfur (S) with -bromosuccinimide (NBS) and -chlorosuccinimide (NCS) effectively halogenated less-reactive aromatic compounds, such as ester-, cyano-, and nitro-substituted anisole derivatives. No reaction occurred in the absence of S, underscoring its crucial role in the catalytic activity.

A concise synthesis of thioaurones NBS-induced cyclization of MOM-protected 2'-mercaptochalcones.

A mild and efficient approach for the synthesis of thioaurones NBS-induced cyclization of methoxymethyl-protected mercapto-chalcones has been developed. This simple method is highly functional group tolerant and provides straightforward access to thioaurones in good to high yields.

Selective synthesis of 3-formylbenzofuran and 3-acylbenzofuran using a chalcone rearrangement strategy.

We developed a method for highly selective synthesis of two benzofuran isomers, by rearranging and subsequently transforming 2-hydroxychalcones. Depending on the reaction conditions, synthesis of 3-formylbenzofurans, unconventional products, and 3-acylbenzofurans was achieved through cyclized 2,3-dihydrobenzofurans obtained from the rearranged products. The facile synthesis of 3-formylbenzofurans facilitated synthesis of the natural product, puerariafuran, from the corresponding chalcone.

An Improved and Practical Method for Synthesizing of α-Sanshools and Spilanthol.

An efficient and practical route for the synthesis of α-sanshools and spilanthol is described herein. Several modifications of an existing method enabled the preparation of the (2,6,8,10)-tetraene precursor of hydroxy-α-sanshool in good yield. A highly selective Wittig reaction employing newly synthesized phosphonium salt with low deliquescence and long-term stability yielded the desired -form tetraene.

Aromatic Halogenation Using N-Halosuccinimide and PhSSiMe or PhSSPh.

We developed a mild aromatic halogenation reaction using a combination of N-halosuccinimide and PhSSiMe or PhSSPh. Less reactive aromatic compounds, such as methyl 4-methoxybenzoate, were brominated with PhSSiMe or PhSSPh and N-bromosuccinimide in high yields. No reaction was observed in the absence of PhSSiMe or PhSSPh.

Highly Discriminative and Chemoselective Deprotection/Transformations of Acetals with the Combination of Trialkylsilyl Triflate/2,4,6-Collidine.

Acetals are the most useful protecting groups for carbonyl functional groups. In addition to the role of protection, they can also be used as synthons of carbonyl functions. Previously, we developed a chemoselective deprotection and nucleophilic substitution of acetals from aldehydes in the presence of ketals.

Direct Synthesis of Chalcones from Anilides with Phenyl Vinyl Ketones by Oxidative Coupling Through C-H Bond Activation.

A novel approach for synthesizing chalcones by Pd-catalyzed oxidative coupling is described. This is the first report of the efficient coupling reaction of acetanilides with phenyl vinyl ketones under mild conditions. Selective C-H activation occurred next to the acetamide group to afford 2-aminochalcone derivatives.

A mild method for synthesizing carboxylic acids by oxidation of aldoximes using hypervalent iodine reagents.

A mild oxidation method for the conversion of aldoximes to carboxylic acids was developed mediated by hypervalent iodine reagents. This method covers a wide range of functionalized aldoximes and proceeds under mild conditions, utilizing PhI(OH)OTs as an oxidant.

Catalyst-Dependent Selective Hydrogenation of Nitriles: Selective Synthesis of Tertiary and Secondary Amines.

In the presence of palladium on carbon (Pd/C) as a catalyst, hydrogenation of aliphatic nitriles in cyclohexane efficiently proceeded at 25-60 °C under ordinary hydrogen gas pressure to afford the corresponding tertiary amines. However, the use of rhodium on carbon (Rh/C) led to the highly selective generation of secondary amines. Hydrogenation of aromatic nitriles and cyclohexanecarbonitrile selectively produced secondary amines in the presence of either Pd/C or Rh/C.

Synthesis of 3-acylindoles by oxidative rearrangement of 2-aminochalcones using a hypervalent iodine reagent and cyclization sequence.

An efficient one-pot method was developed for the construction of 3-acylindoles via oxidative rearrangement of 2-aminochalcones followed by intramolecular cyclization. The reaction was used to convert a variety of 2-aminochalcones into 3-acylindoles in moderate to high yields.

Transformation of Methylene Acetals to Bromoformates with a Combination of Trimethyl(phenylthio)silane and N-Bromosuccinimide.

A novel transformation reaction of methylene acetals, using a combination of trimethyl(phenylthio)silane (PhSTMS) and N-bromosuccinimide (NBS) under mild reaction conditions, is described. Various methylene acetals were converted to their corresponding bromoformates in good to high yields. Under the given conditions, the reaction proceeded via a radical pathway.

[Cu(OH)(TMEDA)]₂Cl₂-catalyzed regioselective 2-arylation of 5-substituted tetrazoles with boronic acids under mild conditions.

A mild and regioselective 2-arylation of 5-substituted tetrazoles is described. The reaction proceeds regioselectively with a variety of arylboronic acids in the presence of [Cu(OH)(TMEDA)]2Cl2 to afford 2,5-disubstituted tetrazoles. This is the first report of highly regioselective arylation of 5-alkyltetrazoles.

Methylene acetal formation from 1,2- and 1,3-diols using an O,S-acetal, 1,3-dibromo-5,5-dimethylhydantoin, and BHT.

A mild and efficient method for formation of methylene acetals from 1,2- and 1,3-diols using methoxymethylphenylsulfide, 1,3-dibromo-5,5-dimethylhydantoin (DBDMH), and dibutylhydroxytoluene (BHT) is described. The use of BHT in this process suppresses side reactions and enables high-yielding formation of methylene acetals of various diols, including carbohydrate-type substrates.

Method for the efficient synthesis of highly-substituted oxetan- and azetidin-, dihydrofuran- and pyrrolidin-3-ones and its application to the synthesis of (±)-pseudodeflectusin.

Highly substituted four- and five-membered heterocycles were prepared starting with O,P- and N,P-acetals by using a one-pot method involving base induced cyclization and a Horner-Wadsworth-Emmons (HWE) olefination reaction. Divergent synthesis of various heterocycles was achieved by using this method and transformations of the alkenyl group in the products of these processes were exemplified. Finally, a short and efficient synthesis of (±)-pseudodeflectusin based on the new methodology was achieved.

Effects of phosphorus substituents on reactions of α-alkoxyphosphonium salts with nucleophiles.

The effects of phosphorus substituents on the reactivity of α-alkoxyphosphonium salts with nucleophiles has been explored. Reactions of α-alkoxyphosphonium salts, prepared from various acetals and tris(o-tolyl)phosphine, with a variety of nucleophiles proceeded efficiently. These processes represent the first examples of high-yielding nucleophilic substitution reactions of α-alkoxyphosphonium salts.

(+)-Sorangicin A: evolution of a viable synthetic strategy.

An effective, asymmetric total synthesis of the antibiotic (+)-sorangicin A (1) has been achieved. Central to this venture was the development of first and second generation syntheses of the signature dioxabicyclo[3.2.

Reaction of acetals with various carbon nucleophiles under non-acidic conditions: C-C bond formation via a pyridinium-type salt.

Mild substitution reactions of acetals with carbon nucleophiles via the pyridinium-type salts generated by the treatment of acetals with TESOTf-2,4,6-collidine or 2,2'-bipyridyl have been developed. Various carbon nucleophiles, such as organocuprates, silyl enol ethers, enamines, etc., reacted with the pyridinium-type salts to give the corresponding substituted products in good yields.

Selective N-alkylation of amines using nitriles under hydrogenation conditions: facile synthesis of secondary and tertiary amines.

Nitriles were found to be highly effective alkylating reagents for the selective N-alkylation of amines under catalytic hydrogenation conditions. For the aromatic primary amines, the corresponding secondary amines were selectively obtained under Pd/C-catalyzed hydrogenation conditions. Although the use of electron poor aromatic amines or bulky nitriles showed a lower reactivity toward the reductive alkylation, the addition of NH(4)OAc enhanced the reactivity to give secondary aromatic amines in good to excellent yields.

An unusual reaction of α-alkoxyphosphonium salts with Grignard reagents under an O2 atmosphere.

An unusual and novel reaction of α-alkoxyphosphonium salts, generated from O,O-acetals and Ph(3)P, with Grignard reagents under an O(2) atmosphere afforded alcohols in moderate to high yields. It was clarified by isotopic labelling experiments that the reaction proceeded via a novel radical pathway.

2,5-cis-2,3,5-Trisubstituted tetrahydrofurans from the diastereomixture of 2,4-disubstituted 1,3-dioxepins via stereomutation.

A diastereoselective ring contraction of the diastereomixture of 2,4-disubstituted 1,3-dioxepins to 2,5-cis-2,3,5-trisubstituted tetrahydrofurans was achieved using TfOH in DMF. The reaction appears to proceed via a chair-like transition state, in which stereomutation of the oxocarbenium occurred, followed by an aldol-type cyclization.

Direct conversion of acetals to esters with high regioselectivity via O,P-acetals.

A new direct conversion of O,O-acetals to esters via O,P-acetal intermediates was developed. The regioselective cleavage of unsymmetrical cyclic acetals occurred to give the more crowded esters as single isomers.

Palladium on carbon-catalyzed synthesis of 2- and 2,3-substituted indoles under heterogeneous conditions.

A mild, efficient and LiCl-free synthetic method for indole derivatives based on the heteroannulation of alkynes with 2-iodoanilines was achieved using palladium on carbon (Pd/C) and NaOAc in heated NMP. The N-tosyl protection of 2-iodoaniline expedited the reaction progress, while other protecting groups, such as tert-butoxycarbonyl, acetyl, and benzyloxycarbonyl groups, underwent deprotection under the present conditions. A variety of di- and monosubstituted alkynes could effectively react with N-tosyl-2-iodoaniline to give the corresponding indoles in good to high yields.

Remarkable effect of phosphine on the reactivity of O,P-acetal--efficient substitution reaction of O,P-acetal.

The structure and electronic nature of the phosphine have a significant influence on not only the formation, but also the subsequent transformation of O,P-acetals. The O,P-acetals generated from tris(o-tolyl)phosphine [(o-tol)(3)P] underwent efficient substitution reactions with various nucleophiles.