Regio- and diastereoselective synthesis of 2-alkylidenetetrahydrofurans by domino SN/SN' and SN/SN reactions of 1,3-dicarbonyl dianions

The domino C,O-cyclodialkylation reaction of dilithiated 1,3-dicarbonyl compounds with 1,4-dibromo-2-butene resulted in regio- and diastereoselective formation of 2-alkylidene-5-vinyltetrahydrofurans. The cyclization of 1,3-dicarbonyl dianions with 1-bromo-2-chloroethane regio- and diastereoselectively afforded 2-alkylidenetetrahydrofurans under thermodynamic reaction control.     

Regio- and diastereoselective cyclization reactions of free and masked 1,3-dicarbonyl dianions with 1,2-dielectrophiles

Despite their simplicity and synthetic usefulness, cyclisation reactions of 1,3-dicarbonyl dianions with 1,2-dielectrophiles are problematic, since both dianions and 1,2-dielectrophiles are highly reactive compounds (low reactivity matching). In addition, 1,2-dielectrophiles are often rather labile, and reactions with nucleophiles can result in polymerisation, decomposition, formation of open-chained products, elimination or SET-reactions. These intrinsic limitations can be overcome by a proper reactivity tuning and by the use of electroneutral dianion equivalents (masked dianions) in Lewis acid catalysed reactions. The cyclisations reported herein allow for an efficient, regio- and stereoselective one-pot synthesis of biologically relevant ring systems.     

Synthesis of fluorinated 2,3-dihydropyran-4-ones by cyclocondensation of 1,3-dicarbonyl dianions with aldehydes

The reaction of the dianion of 1,1,1-trifluoro-pentane-2,4-dione with aldehydes and subsequent addition of hydrochloric acid afforded 2,3-dihydro-6-trifluoromethyl-pyran-4-ones. The reaction of the dianion of acetylacetone with fluorinated benzaldehydes gave the corresponding fluorinated 2-aryl-2,3-dihydro-6-methyl-pyran-4-ones. All reactions proceeded in very good yield and with very good regioselectivity.     

Regio- and stereoselective synthesis of novel tetraspiro-bispyrrolidine and bisoxindolopyrrolidine derivatives through 1,3-dipolar cycloaddition reaction

An efficient approach to the synthesis of a new class of tetraspiro-bispyrrolidines and tetraspiro-bisoxindolopyrrolidines has been accomplished through 1.3-dipolar cycloaddition reaction. The reported method is a one-pot, three component reaction, that is, run under solvent-free microwave conditions.     

Efficient and regioselective synthesis of functionalized pyrroles by cyclocondensation of 1,3-dicarbonyl dianions with alpha-azidoketones

The cyclocondensation of 1,3-dicarbonyl dianions with alpha-azidoketones regioselectively afforded 2-alkylidenepyrrolidines which were transformed into functionalized pyrroles by treatment with acid.     

Lewis acid mediated thienium cation diels-alder reaction: A new method for regio- and stereoselective functionalization of 1,3-dienes

Under the influence of aluminum chloride the β-ethylthionitroolefin results in the formation of the thienium cation, which reacts with a variety of 1,3-dienes in the Diels-Alder sense. The cleavage of the resulting ring provides in one pot the 1,4-functionalized olefins in regio- and stereoselective manner.     

Regio- and stereoselective synthesis of spiro-pyrrolidine/pyrrolizidine/thiazolidine-grafted macrocycles through intramolecular 1,3-dipolar cycloaddition reaction

Regioselective synthesis of spiropyrrolidine-grafted 11-membered macrocycle was accomplished through an intramolecular [3+2] cycloaddition of azomethine ylides. The key precursor alkenyl diketone (4a–b) was obtained from simple starting materials. The dipole generated from isatin tethered to O-alkyl enone (4a–b) was reacted intramolecularly to yield the spiropyrrolidine-grafted macrocycles (6a–b). The structures of the cycloadducts were assigned by 2D NMR and confirmed by single crystal analysis.     

Regio- and stereoselective nickel-catalyzed homoallylation of aldehydes with 1,3-dienes

Ni(acac)(2) catalyzes homoallylation of aldehydes with 1,3-dienes in the presence of triethylborane. Triethylborane serves as a reducing agent delivering a formal hydride to the C2 position of 1,3-dienes, thus generating a formal homoallyl anion species and enabling the novel homoallylation of aldehydes. The reaction proceeds smoothly at room temperature in the absence of any phosphane or nitrogen ligands and is highly regioselective and stereoselective for a wide variety combination of aldehydes and 1,3-dienes: e.g., isoprene and benzaldehyde combine to give a mixture of anti- and syn-1-phenyl-3-methyl-4-penten-1-ol (2.2) in a ratio of 15:1 in 90% yield. Under the conditions, sterically congested aliphatic aldehydes and ketones show low yields. In such cases, diethylzinc serves as a substitute for triethylborane and yields the expected products in good yields with similarly high regio- and stereoselectivity. 1,3-Cyclohexadiene is one exception among 24 kinds of dienes examined and undergoes allylation (not homoallylation) selectively.     

Synthesis of 2-alkylidenepyrrolidines and pyrroles by condensation of 1,3-dicarbonyl dianions with alpha-azidoketones and subsequent intramolecular Staudinger-aza-Wittig reaction

The condensation of 1,3-dicarbonyl dianions with alpha-azidoketones afforded open-chained condensation products that were transformed into pyrroles by Staudinger-aza-Wittig reactions and the subsequent treatment with trifluoroacetic acid.     

Regioselective synthesis of functionalized ferrocenylphenols based on cyclocondensation reactions of free and masked 1,3-dicarbonyl dianions

Highly functionalized ferrocenyl-substituted phenols were prepared by cyclization of masked or free dianions with 1,3-dielectrophilic 1-η5-ferrocenyl-3,3-bis(methylthio)prop-2-en-1-ones. While the cyclizations of 1,3-bis(silyloxy)-1,3-butadienes (masked dianions) proceed by initial 1,2-addition, the reactions of free 1,3-dicarbonyl dianions proceed by initial 1,4-addition. Therefore, both regioisomeric ferrocenylphenols are available from one and the same electrophile dependent on the type of nucleophile and reaction conditions employed. The reactions reported represent the first examples of the application of formal [3 + 3] cyclizations to the synthesis of organometallic compounds.     

Regio- and stereoselective Ferrier reaction of O-1,3-dienyl acetals promoted by organoaluminum complexes

The Ferrier reaction of O-1,3-dienyl acetals promoted by organoaluminum complexes such as methylaluminum bis(2,6-di-tert-butyl-4-methylphenoxide) (MAD) is shown to proceed with a high degree of regio- and stereoselectivity to afford the corresponding alpha-alkenyl-substituted beta-alkoxy aldehydes in good yields. The mechanistic origin of the high regiocontrolling ability of MAD is elucidated. This method, coupled with the easy availability of the requisite substrates, expands the synthetic scope of the Ferrier reaction. [reaction: see text].     

Lewis acid mediated reactions of aldehydes with styrene derivatives: synthesis of 1,3-dihalo-1,3-diarylpropanes and 3-chloro-1,3-diarylpropanols

[reaction: see text] The reactions of aryl aldehydes with styrene derivatives, mediated by various boron Lewis acids, were investigated. 1,3-Dihalo-1,3-diarylpropanes were obtained in high yields with boron trihalides, while 3-chloro-1,3-diarylpropanols were obtained in good to excellent yields with phenylboron dichloride. Reactions involving nonenolizable aliphatic aldehydes, trans-cinnamaldehyde, and beta-substituted styrenes were also investigated for the first time.     

Regio- and stereoselective synthesis of novel (E)-1-alkenyl carbamate via carbocupration reaction

The stereoselective carbocupration and copper-catalyzed carbomagnesiation reactions of alkynyl carbamates are described as a new and straightforward method for the preparation of (E)-alkenyl enol carbamates. [reaction: see text]     

Regio- and stereoselective synthesis of (E)-1-bromo-2-iodoalkenes through iodobromination of internal alkynes

One-step synthesis of (E)-1-bromo-2-iodoalkenes from internal alkynes through IBr addition is described. The IBr was generated in situ from commercially available TMSBr and NIS. This simple protocol enables highly efficient regio- and stereoselective iodobromination of the triple bond on a gram scale in anti-mode, and provides a potentially diverse scaffold for preparation of differentially all-carbon tetrasubstituted olefins.     

Regio- and stereoselective synthesis of the enantiomers of monoterpene-based β-amino acid derivatives

The regio- and stereospecific addition of chlorosulfonyl isocyanate to cis-δ-pinene enantiomers has furnished monoterpene-fused β-lactams. The observed regioselectivity can be explained by ab initio DFT modeling of transition state structures. In contrast with the less reactive α-pinane-fused β-lactam 4, the resulting β-lactams 5 and 13 containing an amino group connected to a secondary carbon possess similar reactivity to the cycloalkane-fused analogues and can be easily converted to the β-amino acid and its protected derivatives. The base-catalyzed isomerization of the cis-amino ester afforded the corresponding trans-amino ester in moderate yield.     

Samarium dienolate mediated stereoselective synthesis of anti-1,3-diol monoesters via aldol-Tishchenko reaction

The reaction of an (E)-samarium dienolate, generated by the regioselective reductive cleavage of a phenylsulfonyl activated cyclopropyl ketone with samarium(II) iodide, with aliphatic and aromatic aldehydes gives the 2-substituted anti-1,3-diol monoester derivatives, stereoselectively, in good to excellent yields. The results represent the first report of a dienolate in the aldol-Tishchenko reaction and also provide an optically active polyol with (R)-glyceraldehyde.     

Regio- and stereoselective synthesis of isoindolin-1-ones via electrophilic cyclization

[reaction: see text] A variety of substituted isoindolin-1-ones are readily prepared in good to excellent yields under very mild reaction conditions by the reaction of o-(1-alkynyl)benzamides with ICl, I(2), and NBS. In a few cases, substituted isoquinolin-1-ones were obtained as the major product instead. This methodology accommodates various alkynyl amides and functional groups and has been successfully extended to heterocyclic starting materials. This chemistry has been successfully applied to the synthesis of a biologically interesting alkaloid, cepharanone B.     

Regio- and stereoselective synthesis of functionalized oxazolidin-2-ones from the reaction of α-epoxyketones with urea

A regio- and stereoselective synthesis of functionalized 4,5-disubstituted oxazolidin-2-ones is reported with moderate to good yields from the reaction of α-epoxyketones with urea in the presence of p-toluenesulfonic acid as the catalyst.     

Regio- and stereoselective synthesis of functionalized oxazolidin-2-ones from the reaction of α-epoxyketones with urea

A regio- and stereoselective synthesis of functionalized 4,5-disubstituted oxazolidin-2-ones is reported with moderate to good yields from the reaction of α-epoxyketones with urea in the presence of p-toluenesulfonic acid as the catalyst. Correspondence: Farzad Nikpour, Department of Chemistry, Faculty of Sciences, University of Kurdistan, P.O. Box 66315-416, Sanandaj, Iran.     

Tetrabutylammonium hydrogen sulfate mediated domino reaction: synthesis of novel benzopyran-annulated pyrano[2,3-c]pyrazoles

A tetrabutylammonium hydrogen sulfate (TBA-HS) mediated procedure for one pot synthesis of novel benzopyran-annulated pyrano[2,3-c]pyrazoles via domino/Knoevenagel-hetero-Diels-Alder reaction has been demonstrated.