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A series of various poly-substituted benzoxazoles were synthesized starting from readily available carboxylic acids. The method is based on TCT (cyanuric chloride)/microwave acid activation and it is characterized by mild conditions, allowing for a wide range of starting materials and functionalization of final products.

In light of the growing scarcity of petroleum-based raw materials, carbon dioxide (CO 2 ) is becoming increasing attractive as organic carbon source. In this perspective, formic acid (HCOOH) might be an interesting bio-renewable solution to store, transport, and activate carbon dioxide for the synthesis of value-added chemicals. Herein, HCOOH has been successfully used as C1 building block for the synthesis of a library of alcohols via a catalysed oxo-synthesis, under green experimental conditions.

A one-pot synthesis of amides from aldheydes with N-chloroamines, prepared in situ from amines, has been developed. Both aliphatic and aromatic aldehydes and many types of mono- and disubstituted amines are tolerant in this transformation. This cross-coupling reaction appears simple and convenient, has a wide substrate scope and makes use of cheap, abundant, and easily available reagents.

An easy and rapid procedure for the preparation of N-monosubstituted ureas via reaction between potassium cyanate and a wide range of amines is described. The procedure was performed under microwave irradiation using water as solvent. This methodology is particularly attractive since it provides ureas in high yield and purity.

A novel and efficient synthetic procedure for converting a diverse set of amines to N,N′ -di-Boc-protected guanidines is described. The methodology comprises the use of cyanuric chloride (TCT) as activating reagent for di-Boc-thiourea. The employ of inexpensive TCT instead of classical HgCl 2 eliminates the environmental hazard of heavy-metal waste without appreciable loss of yield or reactivity. This protocol provides an alternative route for the guanylation of amines from those currently employed.

t: A series ofPiloty's acid derivatives were easily prepared under mild and neutral conditions. The ease of isolation of the final product offers a marked advantage over well-known procedures. This methodology is particularly attractive as it cleanly provided low molecular weight aliphatic sulfohydroxamic acids, which are very interesting for their tendency to generate HNO under physiological conditions.

In their structural multiplicity and in the extent to which they occur in nature the derivatives of benzofuran are significantly lesser than the isoelectronic analogue indoles. However, these heterocyclic compounds show a variety of pharmacological properties, and change of their structure offers a high degree of diversity that has proven useful for the search of new therapeutic agents. The broad spectrum of pharmacological activity in individual benzofurans indicates that this series of compounds is of an undoubted interest. From this point of view, synthetic methods may be of very useful aid in the production of specific structures characterized by given pharmacological qualities. Moreover from a drug discovery perspective, synthesis of chiral functionalized substituted benzofurans could be more interesting because they might constitute starting materials for the production of biologically active compounds. Taking into account the actual tendency directed toward the development of enantiomerically pure drugs, indeed there is a limited number of papers related to the preparation of enantiomers of benzofuran containing compounds, likely because of difficulties in their preparation with conventional methods. In this context, new approaches seem to expand the potentiality of the synthesis of substituted benzofurans, providing also convenient routes to enantiopure 2-substituted benzofurans.

A simple and chemoselective method for direct bromination of (hydroxymethyl)phenols via reaction with 2,4,6-trichloro[1,3,5]triazine in N,N -dimethylformamide at room temperature is described. The reaction occurs without affecting the phenolic hydroxy group.

A straightforward synthesis of orthogonally protected PNA monomers is described. Protected aminoethylglycine (Aeg) monomers were efficiently prepared by reductive amination of N-Fmoc-glycinaldehyde with glycine methyl ester and the subsequent acylation of the free amine with N-bis-Boc-protected nucleobase acetic acids. The exocyclic amine group of the nucleobases, including the notoriously difficult-to-protect guanine nucleobase, was protected with a bis-Boc carbamate group; this increased the solubility of the nucleobases in the most common organic solvents. The current protocol allows all Aeg monomers to be prepared on both the micro- and macroscale, which avoids or minimizes the use of toxic reagents or solvents, and moreover, cheap starting materials are used.

A focused library of formamidines having several diversity points has been prepared. The use of isocyanate resin as scavenger may offer several practical advantages over conventional procedures, such as the ease of workup and availability. The technique described herein was performed in a parallel synthesis format. The whole protocol has potential use in high throughput synthesis for the preparation and purification of libraries of unsymmetrical formamidines containing sets of different aliphatic substituents.

A microwave-enhanced procedure for the synthesis of substituted benzofurans starting from 2-(1-hydroxyalkyl)-phenols and using triphenylphosphine polystirene resin is reported. The benzofurans are isolated in good to high yields and purities by simple workup. The procedure can be applied to chiral alpha-alkyl-2-benzofuranmethanamines too.

A variety of 3-aryl-4-formylpyrazoles can be easily prepared in good yields from the corresponding methyl ketones, upon treatment with 2,4,6-trichloro[1,3,5]triazine in N,N-dimethyl formamide at room temperature. This kind of pyrazole can constitute new building blocks for combinatorial chemistry.

A resin capture and release strategy for making a combinatorial array of 2,4,5-trisubstituted pyrimidines is demonstrated by capturing beta-ketoesters and beta-ketoamides on a solid-supported piperazine. Through a cyclocondensation reaction, the solid-supported enaminone is reacted with several guanidines under heating or microwave irradiation affording the corresponding pyrimidines in good yield and chemical purity directly on solution. After this final step, the support can be effectively recycled.

A cellulose-based resin has been used to prepare a library of pyrazoles and isoxazoles via in situ generation of a polymer-bound enaminone. The synthesis is more versatile and efficient than the methods that had been previously described. Treatment of cellulose-bound enaminone with hydroxylamine or phenylhydrazine afforded the corresponding isomerically pure target heterocycles in high yield directly in solution, restoring the starting cellulose. To cite this article: L. De Luca et al., C. R. Chimie 6 (2003).

A general synthesis of a new class of optically active amino acids containing an oxazole moiety is described along with a strategy for their insertion into a peptidomimetic chain. A modified portion of endothelin-1 is prepared as a potential receptor antagonist. The procedure presented is based on readily available materials and can be performed in multigram quantities.

A series of novel optically active α-amino acids, containing a pyrazole ring, which can be regarded as building blocks for peptidomimetics, have been prepared starting from readily available α-amino acids. The synthetic strategy employed allows the regio- and stereoselective preparation of 1,3- or 1,5-substituted pyrazolyl rings. The pyrazole containing peptidomimetics can be considered as analogues of peptides with a cis amide bond.

Methodology for preparing a series of novel α-amino-acids and their derivatives containing an isoxazole ring as a substituent is presented. The synthesis starts from a readily available l -serine derivative from which, depending on the synthetic strategy, it is possible to obtain isoxazol-3-yl or isoxazol-5-yl amino-acid precursors.

The synthesis of tri-functionalized orthogonally protected CRAB templates based on the triazine skeleton are described together with some protocols for the preparation of families of diversomers using a parallel synthesis approach.

A stereospecific syntheses of optically active pyrazoles and isoxazoles from L-proline is described. The procedure presented is based on readily available materials and can be used for preparing new conformationally restricted pyrazole-containing amino acids.

Enantiospecific syntheses of optically active amino acids containing an oxazole moiety are described. Two different strategies for their insertion in a peptidomimetic chain are also discussed. The procedures presented are based on materials readily available in multigram quantities.

Angeli-Rimini's reaction has been performed for the first time on solid phase. A convenient one-step procedure for the synthesis of hydroxamic acids starting from aldehydes and solid-supported N-hydroxybenzenesulfonamide is reported. The hydroxamates are isolated in good to high yields and purities by simple evaporation of the volatile solvents, after treatment of the crude reaction mixture with sequestering agents.

General stereospecific syntheses of the optically active title compounds are described. The procedures presented are based on readily available starting materials, such as piperazine alcohols, and can be arranged for multigram quantities.

A series of various poly-substituted benzoxazoles were synthesized starting from readily available carboxylic acids. The method is based on TCT (cyanuric chloride)/microwave acid activation and it is characterized by mild conditions, allowing for a wide range of starting materials and functionalization of final products.

Cyclic β-amino alcohols 1–4 derived from natural α-amino acids were used as chiral ligands in oxazaborolidine reduction of ketones. The processes were carried out in the presence of various achiral tertiary amine: better resuts are achieved by N , N -diethylaniline.

A procedure for the preparation of optically active (2 R ,5 S )- and (2 S ,5 S )-2-Carboxy-1,4-diaza-[4.3.0]bicyclononane is described. The method is based on the reduction of diketopiperazines obtained from cyclization of Pro-L-Ser or Pro-D-Ser and occurs without loss of enantiomeric purity. The synthesis is based on readily available starting materials and can be easily arranged for multigram scale preparations.

Starting from l -serine and l -threonine, (S)-diphenyl-(2,2-dimethyl-1,3-oxazolidin-4-yl)-methanol and (4S,5R)-diphenyl-(2,2-dimethyl-5-methyl-1,3-oxazolidin-4-yl)-methanol were prepared in good yields. The use of these compounds as very efficient chiral catalysts for the enantioselective addition of diethylzinc to aldehydes is described. This paper reports the first example of the use of oxazolidine methanols in asymmetric synthesis.

Aliphatic and aromatic aldehydes and a series of mono-or disubstituted amines can be used for the process.

( μ 2 -RC 2 R′)Co 2 (CO) 6 complexes are prepared where R ≠ R′ and one of these substituents is a chiral organic group. The structures of the 11 complexes (10 new) range from the simplest possible chiral acetylenic hydrocarbon derivative (S-3-methyl-1-pentyne 1a ) to ethynylsteroid ( 1f, 1g, 1h ) and ethynylcodeine ( 1i, 1j, 1k ) derivatives. The CD spectra are reported and the results are analysed in terms of a quadrant rule. The CD spectra show that in all complexes the Co 2 (CO) 6 fragment of the molecule gets chirally perturbed. The reasons for the chiral perturbation include apolar repulsing (dominant for the hydrocarbon acetylenes) and polar attractive (“autosolvation”; dominant for acetylenes with polar hetero-atom containing substituents) forces.

A very simple procedure for the preparation of chiral optically active N-protected-4-carboxy-1,3-oxazolidine (4-oxaproline) derivatives starting from serine and threonine is described which avoids the use of toxic solvents or reagents. Elaboration of these compounds allows significant improvement in the handling of serine and threonine during the multigram preparation of oligopeptide structures and affords versatile chiral building blocks for the organic synthesis.

Efficient oxidation of primary alcohols to the corresponding carboxylic acids can be carried out at room temperature and in acetone/water, using trichloroisocyanuric acid (TCCA) in the presence of catalytic TEMPO. The mild conditions of this procedure and the total absence of any transition metal make this reaction suitable for safe laboratory use. A possible mechanism is presented and discussed.

Optically active 2-alkyl-2-oxazoline-4-carboxyamides, derived from enantiomeric pure α-amino-β-hydroxy acids, react with aryl- and alkyl sulphonyl chlorides in pyridine affording the corresponding optically active 2-alkyl-2-oxazoline-4-carboxyamido- N -sulphonyl derivatives without appreciable racemization.

An improved synthesis of 2-(2′-pyridyl)-2-aminoalcohols 1a and 1b, in enantiomerically pure form via 1,3-oxazolidine derivatives is presented. Some efficient and selective methods for both the cleavage of the oxazolidine ring and the removal of the N-Boc protecting group are also reported.

The synthesis of a new class of optically active ligands such as the title compounds is presented. All the multistep procedures adopted start by the conversion of L-serine and L-threonine into the proper 2,2-dimethyloxazolidines, followed by transformation of the corresponding nitriles to pyridines. The reaction sequence occurs without loss of enantiomeric purity and with overall satisfactory yield.

General and convenient syntheses of optically active 5-alkylpiperazine- 2-carboxylic acids are described. The methods are based on cyclization of L- or D-serine with α-amino acids and occur without loss of optical purity. The presented procedures are based on readily available starting materials and can be arranged for multigram quantities

[reaction: see text] Efficient conversion of alcohols and beta-amino alcohols to the corresponding chlorides (and bromides) can be carried out at room temperature in methylene chloride, using 2,4,6-trichloro[1,3,5]triazine and N,N-dimethyl formamide. This procedure can also be applied to optically active carbinols.

The present new method for the palladium-catalyzed N-alkylation of anilines with tertiary amines occurs under heterogeneous transfer-hydrogenation conditions.

Starting from enantiomerically pure serine, a series of (2 R ,5 S ) and (2 S ,5 S )-2-hydroxymethyl-5-alkyl piperazines 1–5 were prepared in good yields without any racemization. The use of these compounds as chiral catalysts for the enantioselective addition of diethylzinc to aldehydes is described. This paper reports the first example of the use of piperazine methanols in asymmetric synthesis.

[reaction: see text] Carboxylic acids and amino acids are readily converted, under mild conditions, into the corresponding activated esters, which are reacted with Grignard/CuI reagent to give the corresponding ketones in nearly quantitative yields. The compounds were recovered substantially pure from the reaction mixtures.

An easy and rapid procedure for the preparation of N-monosubstituted ureas via reaction between potassium cyanate and a wide range of amines is described. The procedure was performed under microwave irradiation using water as solvent. This methodology is particularly attractive since it provides ureas in high yield and purity.

A palladium-catalyzed N-alkylation of anilines with tertiary amines that occurs under heterogeneous transfer-hydrogenation conditions has been developed. This protocol of transamination, which uses a relatively cheap and easily recyclable heterogeneous catalyst, can be efficiently applied to different substrates and is suitable for large-scale preparations.

General syntheses of 1-(2-pyridyl)alkylamines and N-methyl or N,N-dimethyl-1-(2-pyridyl)alkylamines from optically active α-amino acids are described. The presented procedures are based on catalyzed co-cyclotrimerization of the suitable nitriles with acetylene, which can be conducted without loss of optical purity