A new facile synthesis of 3-amidoindole derivatives and their evaluation as potential GSK-3beta inhibitors.

3-Amidoindoles were synthesized from commercially available arylhydrazines and propargylamines over Zn-salt mediated one pot procedure in excellent regioselectivity and up to 94% yield.

Ruthenium-catalyzed selective monoamination of vicinal diols.

The monoamination of vicinal diols in the presence of in situ generated ruthenium catalysts has been investigated. Among the various phosphines tested in combination with [Ru(3)(CO)(12)], N-phenyl-2-(dicyclohexyl-phosphanyl)pyrrole showed the best performance. After optimization of the reaction conditions this system was applied to different secondary amines and anilines as well as a number of vicinal diols. With the exception of ethylene glycol, monoamination of the vicinal diols occurred selectively and the corresponding amino alcohols were obtained in good yields, producing water as the only side product.

N-Dealkylation of aliphatic amines and selective synthesis of monoalkylated aryl amines.

Highly selective alkyl transfer processes of mono-, di- and trialkyl amines in the presence of the Shvo catalyst have been realized; in addition, a general method for N-alkylation of aniline with di- and trialkyl amines is presented.

General zinc-catalyzed intermolecular hydroamination of terminal alkynes.

Catalytic hydroaminations are one of the most sustainable C-N bond-forming processes as a result of 100% atom economy and the availability of substrates. Here, it is shown that the intermolecular hydroamination of terminal alkynes with anilines proceeds smoothly in the presence of catalytic amounts of zinc triflate, an easily available and inexpensive zinc salt. Amination and subsequent reduction with NaBH3CN gives a variety of secondary and tertiary amines in up to 99% yield and with over 99% Markovnikov regioselectivity. Moreover, difficult functional groups such as nitro and cyano substituents are tolerated by the homogeneous catalyst.

Zinc-catalyzed synthesis of pyrazolines and pyrazoles via hydrohydrazination.

A novel regioselective synthesis of aryl-substituted pyrazolines and pyrazoles has been developed. Substituted phenylhydrazines react with 3-butynol in the presence of a catalytic amount of zinc triflate to give pyrazoline derivatives. The resulting products are easily oxidized in a one-pot procedure to the corresponding pyrazoles.

Synthesis of 3-(2-N,N-diethylaminoethoxy)indoles as potential 5-HT6 receptor ligands.

The synthesis of new pharmaceutically interesting 3-(2-N,N-diethylaminoethoxy)indole derivatives is described. Starting from 3-silyloxy-2-methylindoles, deprotection and in situ aminoalkylation provided 3-(2-N,N-diethylaminoethoxy)indoles in good yield. Further sulfonylation of these novel indoles gave access to potential 5-HT(6) receptor ligands.

Efficient palladium-catalyzed synthesis of 3-aryl-4-indolylmaleimides.

Improved palladium catalysts for the Suzuki coupling of 3-bromo-1-methyl-4-(2-methyl-3-indolyl)maleimide have been developed. The coupling of both aryl- and heteroarylboronic acids proceeds smoothly in good to excellent yields at low catalyst loading.

An improved ruthenium catalyst for the environmentally benign amination of primary and secondary alcohols.

The N-alkylation of amines in the presence of different ruthenium catalysts generated in situ was investigated. Among the various catalysts tested, the combination of [Ru3(CO)12] and N-phenyl-2-(dicyclohexylphosphanyl)pyrrole showed the best performance. By applying this novel catalyst, a variety of functionalized alcohols and amines were converted into the corresponding secondary amines in high yield.

Catalytic Markovnikov and anti-Markovnikov functionalization of alkenes and alkynes: recent developments and trends.

The regioselective functionalization of terminal alkenes and alkynes is of utmost importance for the synthesis of a wide variety of organic products. Based on the original observation by Vladimir Markovnikov-the pioneer of this field of research-in the 19th century, the possible regioisomeric products are classified as Markovnikov or anti-Markovnikov products. Contrary to traditional belief, it is nowadays possible to control the regiochemistry of various additions of nucleophiles to alkenes and alkynes by applying different transition-metal catalysts. Recent developments in this area of selective functionalization of alkenes and alkynes are reviewed.

A general study of [(eta5-Cp')2Ti(eta2-Me3SiC2SiMe3)]-catalyzed hydroamination of terminal alkynes: regioselective formation of Markovnikov and anti-Markovnikov products and mechanistic explanation (Cp'=C5H5, C5H4Et, C5Me5).

A general study of the regioselective hydroamination of terminal alkynes in the presence of [(eta5-Cp)2Ti(eta2-Me3SiC2SiMe3)] (1), [(eta5-CpEt)2Ti(eta2-Me3SiC2SiMe3)] (CpEt=ethylcyclopentadienyl) (2), and [(eta5-Cp*)2Ti(eta2-Me3SiC2SiMe3)] (Cp*=pentamethylcyclopentadienyl) (3) is presented. While aliphatic amines give mainly the anti-Markovnikov products, anilines and aryl hydrazines yield the Markovnikov isomer as main products. Interestingly, using aliphatic amines such as n-butylamine and benzylamine the different catalysts lead to a significant change in the observed regioselectivity. Here, for the first time a highly selective switch from the Markovnikov to the anti-Markovnikov product is observed simply by changing the catalyst. Detailed theoretical calculations for the reaction of propyne with different substituted anilines and tert-butylamine in the presence of [(eta5-C5H5)Ti(=NR)(NHR)] (R=4-C6H4X; X=H, F, Cl, CH3, 2,6-dimethylphenyl) reveal that the experimentally observed regioselectivity is determined by the relative stability of the corresponding pi-complexes 10. While electrostatic stabilization favors the Markovnikov performance for aniline, the steric repulsive destabilization disfavors the Markovnikov performance for tert-butylamine.

Biologically active compounds through catalysis: efficient synthesis of N-(heteroarylcarbonyl)-N'-(arylalkyl)piperazines.

A practical route for the synthesis of new biologically active 5-HT(2 A) receptor antagonists has been developed. In only three catalytic steps, this class of central nervous system (CNS) active compounds can be synthesized efficiently with high diversity. As the initial step, an anti-Markovnikov addition of amines to styrenes provides an easy route to N-(arylalkyl)piperazines, which constitute the core structure of the active molecules. Here, base-catalyzed hydroamination reactions of styrenes with benzylated piperazine proceeded in high yield even at room temperature. After catalytic debenzylation, the free amines were successfully carbonylated with different aromatic and heteroaromatic halides and carbon monoxide to yield the desired compounds in good to excellent yields. The two key reactions, base-catalyzed hydroamination of styrenes and palladium-catalyzed aminocarbonylation of haloarenes/heterocycles, showed tolerance towards various functional groups, thereby demonstrating the potential to synthesize a wide variety of new derivatives of this promising class of pharmaceuticals.

Palladium-catalyzed carbonylation of haloindoles: no need for protecting groups.

[reaction: see text] For the first time, palladium-catalyzed carbonylations of unprotected bromoindoles have been performed successfully with different N- and O-nucleophiles. Various indole carboxylic acid derivatives are accessible in excellent yield. For example, aminocarbonylation of 4-, 5-, 6-, or 7-bromoindole with arylethylpiperazines provides a direct one-step synthesis for CNS active amphetamine derivatives.

A dramatic effect of aryloxo ligands on the titanium-catalyzed hydroamination of alkynes.

The aryloxotitanium complex 1 is a highly chemo- and regioselective catalyst for intermolecular hydroamination of terminal alkynes. Branched imines are obtained in good to excellent yield (up to 99%) with various primary aromatic and aliphatic amines. [reaction: see text]