Triflic anhydride-mediated synthesis of oxazoles

N-Acyl amino acid esters undergo triflic anhydride-mediated cyclodehydration to form oxazoles and bisoxazoles in a simple one-pot transformation.     

One-pot Friedel-Crafts/Robinson-Gabriel synthesis of oxazoles using oxazolone templates

[reaction: see text] We report herein a one-pot synthesis of 2,4,5-trisubstituted oxazoles via a Friedel-Crafts/Robinson-Gabriel synthesis using a general oxazolone template. Treatment of the oxazolone template with a range of aromatic nucleophiles provided the highly substituted oxazoles in good yields.     

5-(hydroxymethyl)oxazoles: versatile scaffolds for combinatorial solid-phase synthesis of 5-substituted oxazoles

A scheme combining the preparation of building blocks in solution followed by solid-phase combinatorial chemistry has been developed to side-chain diversify 5-(hydroxymethyl)oxazole scaffold (1) into aryl ethers, thioethers, sulfones, sulfonamides, and carboxamides. Protected heterocyclic scaffolds 2 were linked to the solid phase and N-terminal derivatized using active ester chemistry, providing chemset 4?1-4,1-4?. The free side-chain hydroxyl of 4 was smoothly converted to aryl ethers 6 under Mitsunobu conditions, with a broad range of substituted phenols. Alternatively, quantitative conversion of hydroxyl to bromide followed by displacement with alkyl and aryl thiols gave thioethers 8. Thioethers were optionally oxidized to sulfones 9. Bromide displacement by azide, followed by reduction to amine and acylation with a range of carboxylic acids and sulfonyl chlorides gave carboxamides 11 and sulfonamides 13, respectively. Crude purity at typically >90% was observed for each of the five modifications detailed. A series of 20 compounds, exemplifying each modification, was reprepared, purified, and fully characterized.     

A new synthesis of oxazoles

Oxazoles are prepared from the ketoximes in a single pot sequence.     

A silver-mediated one-step synthesis of oxazoles

A silver-mediated one-step procedure to 2,4-disubstituted and 2,4,5-trisubstituted oxazoles has been developed. The method is complementary to existing technologies, yet provides advantages with regard to simplicity, efficiency, and performance. The silver product can be readily recycled, thus minimizing waste.     

One-pot synthesis of oxazoles using isocyanide surrogates

We wish to present herein a simple one-pot synthesis of 2,5-disubstituted oxazoles, starting from benzyl halides and acyl chlorides. The in situ formation of isocyanides, followed by the addition of an acyl chloride in the presence of a base leads to the desired oxazoles in good yields.     

A versatile synthesis of 2,4-substituted oxazoles

A variety of five-membered ring oxazoles have been synthesised with complete regiocontrol and without the requirement for ring oxidation via a reaction sequence based on a vinyl sulfonamide template.     

Trifluoroacetic acid in the synthesis of thiolcarbamates and s-methyl alkanethioates

The major products of the reaction of 2-bromohexanoic acid with methyl thiocyanate in trifluoroacetic acid are S-methyl 2-bromohexanethioate (II) (55% yield), S-methyl 2,2,2-trifluoroethanethioate (IV) (31% yield), N-trifluoro-acetyltrifluoroacetamide (V) (11% yield), and N-trifluoroacetyl-S-methylthiol-carbamate (III) (29% yield). N-2-Bromohexanoyl-S-methylthiolcarbamate (I), N-2-bromohexanoyltrifluoroacetaraide (VI), 2-thiapropioamide(VII), and S-methyl hex-anethioate (VIII) are also formed in minor amounts.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 195–198, January, 1991.     

Gold-catalysed synthesis of amino acid-derived 2,5-disubstituted oxazoles

Amino acid-derived propargylic amides are cyclised in a one-pot, Au(III)-catalysed operation to yield 5-bromomethyl oxazoles. These compounds are further elaborated to bis-heterocycles, dipeptide mimics and more.     

Trifluoroacetic acid-mediated hydroarylation: synthesis of dihydrocoumarins and dihydroquinolones

[reaction: see text] Trifluoroacetic acid mediates the hydroarylation of alkenes to afford dihydrocoumarins and dihydroquinolones in good yield. Intermolecular hydroarylation of cinnamic acids by phenols is particularly facile, which leads to the conclusion that previous reports of palladium-catalyzed hydroarylation of cinnamic acids in trifluoroacetic acid are erroneous.     

Gold-catalyzed oxazoles synthesis and their relevant antiproliferative activities

Nine 5-aryl-2-methyloxazole derivatives were synthesized via gold-catalyzed alkyne oxidation. All of the compounds have been screened for their antiproliferative activities against MCF-7 cell （human breast carcinoma）, A549 cell （human lung carcinoma） and Hela cell （human cervical carcinoma） lines in vitro. The results revealed that compounds 1b, 1c and 1d exhibited strong inhibitory activities against the MCF-7 cell lines （with ICso values of 4.6, 9.7 and 2.2 μmol/L, respectively）.     

Use of dilithio-tosylmethyl isocyanide in the synthesis of oxazoles and imidazoles

Dilithio-tosylmethyl isocyanide ($\text{2}$) reacts with the carbonyl of unsaturated esters to form oxazoles, unlike tosylmethyl isocyano monoanion which gives pyrroles by reaction with the conjugated carbon-carbon double bonds. Reaction of $\text{2}$ with carbon-nitrogen multiple bonds leads to imidazoles, an example of which is the one-step synthesis of imidazo[5,1-a]isoquinoline from isoquinoline. From $\text{2}$ and pyridine-N-oxide or pyridazine-N-oxide unsaturated ring opened products are obtained.     

PIDA-mediated synthesis of oxazoles through oxidative cycloisomerization of propargylamides

PIDA [phenyliodine(III) diacetate] in AcOH or AcOH-HFIP (hexafluoroisopropanol) efficiently promotes the formation of 2,5-disubstituted oxazoles via the oxidative cycloisomerization of propargylamide derivatives.     

Fully automated continuous flow synthesis of 4,5-disubstituted oxazoles

[Structure: see text] A multipurpose mesofluidic flow reactor capable of producing gram quantities of material has been developed as an automated synthesis platform for the rapid on-demand synthesis of key building blocks and small exploratory libraries. The reactor is configured to provide the maximum flexibility for screening of reaction parameters that incorporate on-chip mixing and columns of solid supported reagents to expedite the chemical syntheses.     

Efficient synthesis of multi-substituted oxazoles under solvent-free microwave irradiation

A new and efficient method for the synthesis of multi-substituted oxazoles from various carbonyl compounds has been developed using sequential treatment of carbonyl compounds with HDNIB and amides such as acetamide or benzamide under solvent-free microwave irradiation conditions.     

Triflic anhydride-mediated tandem formylation/cyclization of cyanoacetanilides: a concise synthesis of glycocitlone alkaloids

A method is presented for the concise synthesis of 3-formyl-4-hydroxyquinolin-2(1H)-ones through triflic anhydride-mediated tandem formylation/cyclization of cyanoacetanilides. This tandem process was successfully used for the rapid syntheses of glycocitlones A and C.     

Trifluoroacetic acid catalyzed dibenzodiazocine synthesis: optimization and mechanism study

Dibenzo[b,f][1,5]diazocines, a class of potential building blocks for novel electrochemical actuators, were synthesized via a novel, efficient acid-catalyzed reaction of 2-acylbenzoisocyanate at room temperature. Real-time NMR analysis and the captured intermediate showed the mechanism was an unprecedented cyclization of the isocyanate with the neighboring acyl group, followed by the dimerization.     

Continuous-flow solid-phase peptide synthesis

We describe a simple manually operated synthesizer for solid-phase peptide synthesis (SPPS). The synthesis is performed on standard polystyrene-based resin in a flow reactor under low-pressure conditions. The usefulness of the present configuration of SPPS is exemplified on the synthesis of two octapeptide and one decapeptide amides.     

Microwave-assisted solid-phase synthesis of peptoids

Microwave irradiation reduces the reaction time for the solid-phase synthesis of peptoids. Under these conditions, coupling of each residue requires only 1 min. The purity and yields of peptoids synthesized in this way are as good as or better than those achieved using standard methods. [reaction: see text]