Investigation of oxacycle formation by base-promoted endo-mode ring-closing reaction of allenes

The base-promoted endo-mode ring closure of electron-withdrawing group-substituted allenes provided the following interesting results: (1) the endo-mode ring-closing reaction of 1-(benzyloxycarbonyl)-1-(ω-hydroxyalkyl)allenes smoothly proceeded during the formation of five-, seven-, and eight-membered rings; (2) base treatment of benzyloxycarbonylallene and sulfonylallene, having a 2-hydroxyethyl group at the C-1 position, in the presence of an aldehyde led to the ring closure and condensation with the aldehyde in one-pot; and (3) endo-mode ring closure of the sulfonylallenes by internal attack of the carboxylate anion afforded the six-membered lactone.     

Furan ring opening-isochromene ring closure: a new approach to isochromene ring synthesis

A new approach toward the synthesis of 1H-isochromenes based on the recyclization of the furan ring in the corresponding ortho-hydroxymethylbenzylfurans is described.     

Heck-type cross-coupling between halo-exo-glycals and endo-glycals: a practical way to achieve C-glycosidic disaccharides

An effective Heck-type cross-coupling reaction between halo-exo-glycals and endo-glycals to achieve C-glycosidic disaccharides has been developed. Using Pd(OAc)₂ as the catalyst, dppp as ligand and K₂CO₃ as base, the reactions gave C-glycosidic products in good to excellent yields with exclusive stereochemistry.     

endo-Mode cyclizations of vinylogous N-acyliminium ions as a route to the synthesis of condensed thiazolidines

endo-Mode cyclizations of vinylogous N-acyliminium ions incorporating heteroatom-based nucleophiles have been examined as a route to the synthesis of condensed thiazolidines. The scope of these reactions and stereochemical outcome are discussed and explained using quantum chemical calculations.     

Wittig olefination and thiol mediated 7-endo-trig radical cyclization: novel synthesis of oxepin derivatives

Thiophenol-mediated 7-endo radical cyclization for the synthesis of seven-membered cyclic ethers is described. This method can be successfully applied to synthesize various benzoxepin derivatives, which are present in many natural products as building blocks. Alkenyl radicals are generated from easily available terminal alkynes and thiophenol.     

A new synthesis of highly functionalized 2H-pyran derivatives

Ethyl oxo-(2-oxo-cycloalkyl)-ethanoates undergo a smooth reaction with triphenylphosphine and dialkyl acetylenedicarboxylates via intramolecular Wittig reaction to produce spiro-cyclobutene derivatives. These spiro systems undergo electrocyclic ring opening reaction to produce electron-deficient 1,3-dienes, which spontaneously cyclize to 2H-pyran derivatives.     

A facile synthesis of the novel thiazolo[3,2-a]pyrimidine derivatives

2-Bromomethyl- and 2-iodomethyl-2,3-dihydrothiazolo[3,2-a]pyrimidin-5-ones are prepared via the reaction of 3-allyl-2-thiouracil derivatives with bromine or iodine chloride, respectively. The 6-bromo and 6-nitro derivatives are synthesized by an electrophilic substitution at C-6 of the thiazolopyrimidine system. As a result, novel 2,3-dihydrothiazolo[3,2-a]pyrimidin-5-one derivatives are obtained. Hydrogen halide elimination from the 2-halomethyl-2,3-dihydrothiazolo[3,2-a]pyrimidin-5-ones is also reported.     

A novel and stereospecific synthesis of (+)-exo-brevicomin

A novel and stereospecific synthesis of (+)-exo-brevicomin is disclosed. The key step of the reaction sequence employs the sulfinyl moiety as an intramolecular nucleophile to functionalize an alkene π-complexed to a bromonium ion.     

Synthesis of 1H-pyrazolo[3,4-d]pyrimidines via solid-phase Aza-Wittig/electrocyclic ring closure reaction

An elegant solid-phase synthetic route of pyrazolo[3,4-d]pyrimidine derivatives via Aza-Wittig/electrocyclic ring closure reaction was developed and validated. By manipulating the R group from the primary amine building block, one can easily prepare the library of pyrazolo[3,4-d]pyrimidine derivatives.     

A novel method for the synthesis of aryl trihalomethyl sulfones and their derivatization: the search for new sulfone fungicides

A novel method for the preparation of bioactive aryl trihalomethyl sulfones is reported. An iodination reaction with iodine bromide is applied for the synthesis of difluoroiodomethyl aryl sulfones. A series of difluoroiodomethylsulfonyl group bearing derivatives is afforded, including nitroanilines and benzimidazoles. Biological studies show high fungicidal activity for a number of the synthesized sulfones.     

A new approach to the synthesis of lysophosphatidylcholines and related derivatives

A new stereospecific synthesis of lysophosphatidylcholines is reported. The sequence relies on orthogonal protection of hydroxyl groups derived from glyceric acid, using fluorenylmethylcarbonate versus tetrahydropyranyl ether functions, that allow regiospecific introduction of substituents to obtain the target phospholipid compound.     

A new flexible strategy for the synthesis of gem-difluoro-bisarylic derivatives and heterocyclic analogues

A new strategy has been designed for the preparation of gem-difluoro-bisarylic derivatives. It starts from easily accessible and reactive gem-difluoro-propargylic intermediates and elaborates the aromatic rings by a Diels-Alder-aromatization sequence. Heterocyclic systems can be also obtained by 1,3 dipolar cycloadditions, affording mixed aromatic/heteroaromatic derivatives with CF₂ as a linker. Since this motif is a bioisostere of O and CO, corresponding bisarylic scaffolds could be of use to prepare chemical libraries of fluorinated analogues of bioactive natural products and/or drugs.     

One-pot synthesis of N-alkyl purine and pyrimidine derivatives from alcohols using TsIm: a rapid entry into carboacyclic nucleoside synthesis

A convenient and efficient one-pot N-alkylation of nucleobases from alcohols using N-(p-toluenesulfonyl)imidazole (TsIm) is described. In this method, treatment of alcohols with a mixture of purine or pyrimidine nucleobase, TsIm, K₂CO₃, and triethylamine in refluxing DMF regioselectively furnishes the corresponding N-alkyl nucleobases in good yields. This methodology is highly efficient for various structurally diverse primary alcohols.     

A convenient synthesis of ortho-ortho disubstituted biphenyls containing an eight-membered lactam ring using radical chemistry

Compound 4 prepared from Isatin in two steps underwent an unusual radical-induced rearrangement reaction to yield 9 as the major product and 10 as the minor component. Compound 9 shows structural similarities to the antimitotic agent rhazinilam and the gamma secretase inhibitor LY411575. The scope of the reaction has been studied by changing the substitutions on the aromatic rings and the mechanism for the formation of 9 and 10 from 4 is suggested.     

Domino Vilsmeier-Haack/ring closure sequences: a facile synthesis of 3-chlorobenzo[b]thiophene-2-carbaldehydes

Vilsmeier’s reagent treatment of substituted diphenacyl sulfides or diphenacyl disulfides has led to the formation of a series of benzfused 3-chlorothiophene-2-carbaldehydes by a Domino Vilsmeier-Haack reaction/ring closure sequence, opening a new route for the synthesis of 3-chlorobenzo[b]thiophene-2-carbaldehydes and their benzfused analogues. A plausible mechanism has been proposed.     

A new synthesis of benzo[b]thiophenes utilizing an interrupted Pummerer reaction

A convenient synthesis of 3-arylbenzo[b]thiophenes utilizing an interrupted Pummerer reaction of 2-(1-arylvinyl)phenyl ethyl sulfoxides is described. Thus, treatment of these sulfoxides, which were readily prepared from 2-sulfanylphenyl ketones or 2-fluoro-5-methoxybenzaldehyde, with acetic anhydride at 100 °C afforded 3-arylbenzo[b]thiophenes in reasonable yields.     

General entries to C-aryl glycosides. Formal synthesis of galtamycinone

Utilizing a general entry we had developed for the synthesis of C-aryl glycosides, we have prepared the juglone derivatives 18-20 as well as the juglone precursor 13. Because 19 had been previously converted in two steps by Suzuki into galtamycinone (1), its preparation constitutes a total synthesis of 1.     

Novel generation and ring closure of 1,3-thiaza-1,3-butadiene S-oxides through thermal cycloreversion of 6H-1,3,5-oxathiazine S-oxides

Heating of 6H-1,3,5-oxathiazine S-oxides efficiently afforded 1,2,4-oxathiazoles through the mechanism involving thermal cycloreversion of the substrates and the subsequent ring closure of the intermediary 1,3-thiaza-1,3-butadiene S-oxides.     

A new entry to functionalized cycloalkylamines: diastereoselective intramolecular amidoalkylation of N,O-acetal TMS ether possessing allylsilane

Highly diastereoselective cyclization (>20:1) as a new entry to functionalized cycloalkylamines has been conducted with acyclic N,O-acetal TMS ethers possessing an allylsilane moiety.     

Remarkably mild and efficient catalytic Sakurai reaction of N-alkoxycarbonylamino sulfones with allyltrimethylsilane using indium(III) chloride

The Sakurai reaction of N-alkoxycarbonylamino sulfones with allyltrimethylsilane in the presence of a catalytic amount of indium(III) chloride at room temperature produces the corresponding protected homoallylic amines in high yields.