An improved and efficient synthesis of 2-substituted 1,4-dihydropyridine derivatives via regiospecific bromination

A highly regioselective conversion of DHP to DHP has been achieved for the first time in high yield. Treatment of the bromide with different nucleophiles under basic conditions produced 2-substituted 1,4-dihydropyridines in high yields and purity.     

A convenient synthesis of 8-substituted indolizines as precursors to 5-substituted cycl{3.2.2}azine derivatives

The synthesis of 8-substituted indolizines is described via a two step process in which a 1,4-diketone, containing a rerf-butyl group, is cyclocondensed with a trialkylsilyl protected pyrrole to provide 5,8-disubstituted indolizines in higher yields than the identical reaction with unprotected pyrrole. Cleavage of the tert-butyl group from the indolizine 5-position, by treatment with 85% phosphoric acid, provides 8-substituted indolizines in good yields. Treatment of 8-substituted indolizines with dimethyl acetylenedicarboxylate, in the presence of palladium-on-carbon, provides novel 5-substituted cycl{3.2.2) derivatives.     

The regiospecific lithiation of aromatic acetals

The dimethylacetal of benzaldehyde and some 3, 3,4 and 3,4,5 oxygenated derivatives thereof are regiospecifically deprotonated at the 2-position by alkyl lithiums. The resulting aryl lithiums provide various 2-substituted benzaldehydes in moderate to excellent yields.     

Synthesis of 5-substituted pyrimidines. ortho-directed lithiation of pyrimidine derivatives

ortho-Directed lithiation of some pyrimidines has been investigated. Treatment of 2- and/or 4-alkoxy or acylaminopyrimidine with lithium 2,2,6,6-tetramethylpiperidide in ether at 0°, followed by quenching with various electrophiles afforded the corresponding 5-substituted pyrimidines.     

An effective one-pot synthesis of 5-substituted tetronic acids

An expeditious one-pot synthesis of 5-substituted tetronic acids from aldehydes and terminal conjugated alkyne as starting materials is described. The entire process embodies two consecutive chemical events: a catalytic domino reaction to build the 1,3-dioxolane scaffolds 5 and a two-step acid-catalyzed trans-acetalization-lactonization reaction to furnish the tetronic acid derivatives 6.     

An expedient synthesis of diversified pyrrolizines and indolizines

A general and rapid synthesis of new families of pyrrolizines and indolizines in good overall yields via an intramolecular [3+2] cycloaddition reaction is described. Diversity of substitutions can be achieved by the appropriate choice of readily available starting materials. The experimental procedures are straightforward and are performed under neutral conditions. New syntheses are also described for the preparation of N-propargylic 2-amino-benzaldehydes and S-propargylic 2-thiobenzaldehydes.     

Flourine directed lithiation in tricarbonylarenechromium(0) complexes: The regiospecific synthesis of polysubstituted arenes.

Lithiation/electrophilic quenching of the isomeric tricarbonylfluoroanisole chromium(O) complexes in combination with nucleophilic displacement of the fluorine by amine and thiolate allows the totally regiocontrolled synthesis of a range of 1,2,3-, 1,2,4-, and 1,2,3,4,5-polysubstituted arenes.     

Synthesis of some new indolizines

The reaction between 4‐dimethylaminopyridine (DMAP) and 2‐bromoacetophenone(s) readily gives 1‐ [2‐(4‐substitutedphenyl)‐2‐oxoethyl]‐4‐(dimethylamino)pyridinium bromide ( 1–14 ). Action of aqueous NaOH on 1–8 generates the corresponding pyridinium ylide ( 15–22 ), which is isolated as a colored stable crystalline solid. Addition of 15–22 to dimethylacetylene dicarboxylate (DMAD) gives dimethyl 3‐(substitutedbenzoyl)‐7‐(dimethylamino)indolizine‐1,2‐dicarboxylate ( 23–30 ) in 46–62% yield.     

Direct synthesis of 5-substituted naphthoquinones

Peri-metalation of 4-(dimethylamino)-1-tert-butyldimethylsilyloxynaphthalene (5) followed by reaction with an electrophile and Jones' oxidation affords 5-substituted naphthoquinones.     

Synthesis of some 8-substituted 5-deazaflavins

Treatment of 8-fluoro-3,10-dimethyl-5-deazaflavin (Ia) with ethyl cyanoacetate in ethanol in the presence of potassium carbonate gave the corresponding 8-(1-cyano-1-ethoxycarbonylmethyl)-5-deazaflavin, which was converted into 3,8,10-trimethyl-5-deazaflavin by refluxing in aqueous dimethylformamide. Treatment of Ia with sodium azide in ethanol yielded 8-azido-3,10-dimethyl-5-deazaflavin (V). Compound V was converted into the corresponding 8-amino-, 8-acetamido-, and 8-benzamido-5-deazaflavins by heating in high boiling alcohols, acetic anhydride, and benzoic anhydride, respectively. Fusion of compound V with dimethyl acetylenedicarboxylate yielded 4,5-bis(methoxycarbonyl)-1-(3,10-dimethyl-5-deazaflavin-8-yl)-1,2,3-triazole.     

A silicon-mediated synthesis of novel 5-substituted 2,4-dimethoxypyrimidines and 5-substituted uracils

A highly efficient and general method for the synthesis of 5-(2-acylethynyl)-2,4-dimethoxypyrimidines starting from 2,4-dimethoxy-5-/2-(trimethylsilyl)ethynyl/pyrimidine is described. The 5-(2-acylethynyl)-2,4-dimechoxypyrimidines have been converted to 5-(2-acyl-1-iodovinyl) uracils and 5-(2-acylethynyl) uracils.     

An improved general synthesis of 4-aryl-5-pyrimidinecarboxylates

We wish to report an improved, general synthesis of 4-aryl-5-pyrimidinecarboxylates 1. Two different routes have previously been reported for the synthesis of examples of this class of pyrimidine carboxylates. The parent compound, ethyl 4-phenyl-5-pyrimidinecarboxylate was prepared in low yield by the reaction of s-triazine with ethyl benzoyl acetate. In addition, the enol ether β-ketoaldehyde synthon, ethyl 2-benzoyl-3-ethoxy-2-propenoate, was reported to give 1a in modest yield when reacted with guanidine (2).     

Reactivity of indolizines in organic synthesis

This review reports the reactivity of indolizines. The reactions section covers, in general, electrophilic, oxidation, reduction, addition, cycloaddition, condensation, and Mannich and multicomponent reactions. The synthesis of bis-indolizines and cyclazines are reported. The reaction mechanisms are discussed.     

One-pot multicomponent synthesis of polysubstituted indolizines

Concise and efficient four-component tandem approaches to polysubstituted indolizines have been developed under metal-free and mild aerobic conditions in refluxing acetonitrile. The mechanism of the novel reactions was proposed involving the formation of pyridinium ylides and α,β-unsaturated ketones with subsequent 1,3-dipolar cycloaddition and aromatization reaction.     

Facile one-pot synthesis of 5-substituted hydantoins

5-Substituted and 5,5-disubstituted hydantoins are synthesised from the corresponding aldehydes or ketones, using a one-pot, gallium(III) triflate-catalysed procedure that is compatible with a range of substrates and solvents.     

Solid-phase synthesis of 5-substituted amino pyrazoles

An efficient method for the solid-supported synthesis of 5-N-alkylamino and 5-N-arylamino pyrazoles is described. This method is general and mild and utilizes readily accessible resin-immobilized beta-ketoamides 2 as starting materials for the preparation of 1. Resin-immobilized beta-ketoamide, aryl-, or alkylhydazine and Lawesson's reagent are suspended in a mixture of THF/Py and heated at 50-55 degrees C to give a resin-bound 5-aminopyrazole, that is liberated from the solid support by treatment with TFA.     

An improved electrochemical method for the synthesis of some benzofuran derivatives

Electrochemical oxidation of catechol and some 3-substituted catechols (1a--c) has been studied in the presence of 2-chloro-5,5-dimethyl-1,3-cyclohexanedione (3) in aqueous solution using cyclic voltammetry and controlled-potential coulometry. The results indicate that the quinones derived from catechols (1a--c) participate in a Michael addition reaction with 2-chloro-5,5-dimethyl-1,3-cyclohexanedione (3) with consumption of only two electrons per molecule of (1a--c) to from the corresponding benzoforans (10a--c). The electrochemical synthesis of benzofurans has been successfully performed at a carbon rod electrode and in an undivided cell with high yields and purity.     

An efficient,regiospecific synthesis of (±)-Daunomycinone

The development of a general strategy for the control ofregiochemistry in the Diels-Alder reactions of substituted naphthazarins is described. Application of this strategy to the synthesis of(±)-daunomycinone (2) employs two successive regiochemically controlled Diels-Alder reactions and leads to a ten-step, regiospecific synthesis of(±)-2 in 36% overall yield (Scheme 4).     

An improved method of amide synthesis using acyl chlorides

A simple, mild and highly efficient condition for amide synthesis from acyl chlorides has been developed to minimize hydrolysis, racemization and other side reactions. This method should expand capabilities in the peptide coupling area.