Regio- and stereoselective synthesis of methyl 5-methylenetetrahydropyran-3-carboxylates from Baylis-Hillman adducts via allyltributylstannane-mediated radical cyclization

Two types of regioisomeric methyl 5-methylenetetrahydropyran-3-carboxylate derivatives 3a-c and 6a-c were synthesized stereoselectively starting from the Baylis-Hillman adducts via the allyltributylstannane-mediated vinyl radical cyclization as the key step.     

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.     

The stereoselective syntheses of 1-aryl-1,6-dideoxyinositol derivatives

This Letter describes the first report of a highly stereoselective synthesis of triethereal cyclohexanones via copper(I) mediated 1,4-addition of organometallic reagents to glucose-derived triethereal cyclohexenone. The cyclohexanones generated can be reduced with modest stereoselectivity to afford a variety of substituted inositol derivatives as potential pyranose sugar mimetics. The protocol generated a range of substituted cyclohexanones in good yield as single stereoisomers.     

Regio- and stereo-selective synthesis of multi-substituted 3-pyrrolines

A regio-and stereo-selective synthesis of multi-substituted 3-pyrrolines has been developed.The multi-substituted 3-pyrrolines were synthesized in good yields by 1,3-dipolar cycloaddition of methyl 2-(phenylselanyl)acrylate with azomethine ylides,followed by N-acylation and oxidation-elimination of phenylseleno group.     

Suzuki-Miyaura cross-coupling reaction of monohalopyridines and l-aspartic acid derivative

Suzuki-Miyaura cross-coupling reaction of halogenated pyridines and a borated l-aspartic acid derivative was conducted. The reactivity of chloro-, bromo-, and iodo-pyridines with substituents at the C2, C3, and C4 positions was investigated. Electron density of halogenated pyridines was also estimated by density functional theory (DFT) calculations. The order of experimental yield of halogen substituents was Br?>?I?>>?Cl and C3?>?C2, C4 whereas the DFT results indicated the reactivity order as I?>>?Br, Cl and C4?>?C2, C3. Optimized experimental conditions (3-bromopyridine) afforded the coupling product quantitatively.     

Regio- and Stereoselective Hydroelementation of SF5-Alkynes and Further Functionalizations.

Herein is described a fully regio- and stereoselective hydroelementation reaction of SF₅-alkynes with N, O and S-nucleophiles and further functionalization of the corresponding Z-(hetero)vinyl-SF₅ intermediates, a suitable platform to access α-SF₅ ketones and esters, β-SF₅ amines and alcohols under mild reaction conditions. Experimental and computational comparative studies between SF₅- and CF₃-alkynes have been performed to highlight and explain the difference of reactivity and selectivity observed between these two fluorinated motifs.     

Cu-catalyzed regio- and stereoselective sulfonylation of multi-substituted allenes

Regio- and stereoselective sulfonylation of allenes under Cu catalysis is described. Allenyl sp carbons exclusively react with TsCN to give the corresponding alkenyl sulfones. The reaction is initiated by addition of tosyl radical to form benzyl radical intermediates, which determines the reaction pathway. The structure of the products is highly dependent on the substituents on allenes.     

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 syntheses of piperidine derivatives via ruthenium-catalyzed coupling of propargylic amides and allylic alcohols

Intermolecular selective coupling of linear allylic alcohols and propargylic amides occurs in the presence of a catalytic amount of the cationic ruthenium complex [Cp*Ru(NCCH(3))(3)]PF(6) followed by condensation to generate six-membered cyclic enamides or hemiaminal ethers with water as the only side product.     

Regio- and stereoselective annelation of phenanthridines with α,β-acetylenic γ-hydroxyacid nitriles

Phenanthridines (3,4-, 7,8-benzoquinolines and methyloctahydrophenanthridine) are annelated regio- and stereoselectively with α,β-acetylenic γ-hydroxyacid nitriles to form new polyfunctional condensed systems, 4-cyanomethylene-1,3-oxazolidino-1,2-dihydrophenanthridines.     

Looking for high‐energy density compounds among hexaazaadamantane derivatives with ?CN, ?NC,and ?ONO2 groups

Density functional theory (DFT) was employed to evaluate the heats of formation (HOFs) for hexaazaadamantane (HAA) derivatives with ? CN, ? NC, and ? ONO₂ groups, respectively. This was done by designing isodesmic reactions at the B3LYP/6‐31G* level of theory, where the HAA cage skeletons were kept unbroken to produce more accurate results, and all HOFs for the required reference compounds, NH₂CN, NH₂NC, NH₂ONO₂, and (CH₂NH)₃, were derived from the G₃ theory calculation based on the atomization energies. The calculation results show that the HOFs of HAA derivatives are mainly affected by the number and the position of substituent groups, all the obtained HOFs are positive, and the ? NC derivatives have the most HOFs among the three types of derivatives with the same number of substituent groups. The detonation velocity (D) and detonation pressure (P) were obtained from the empirical Kamlet–Jacobs equations. All the ? NC and ? CN derivatives of HAA have lower densities (ρ), heats of explosion (Q), D, and P. However, these properties of ? ONO₂ derivatives are rather high and vary with the number of ? ONO₂ groups. Considering the easiness for synthesis and relative stability, 2,4,6,8‐hexaazaadamantanenitrate is finally recommended as a potential candidate of a high‐energy density compound (HEDC). © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006     

CuI/l-proline catalyzed click reaction in glycerol for the synthesis of 1,2,3-triazoles

Despite the apparent simplicity of the copper(I) iodide catalyzed CuAAC reaction, the conversion of the catalytic species, i.e. Cu(I) to thermodynamically more stable Cu(II), via aerial oxidation or disproportionation is a major issue. To stabilize the Cu(I) species, the reaction is ideally carried out under an inert atmosphere in the presence of additives such as alcohols, amines, thiols, and aldehydes. Herein, we report the first CuI catalyzed click reaction without an inert atmosphere by employing the CuI/l-proline system in glycerol. The method showed remarkable stability towards sensitive functional groups such as acetonides and 1,2,4-trioxanes.     

Novel chiral bifunctional l-thiazoline-amide derivatives: design and application in the direct enantioselective aldol reactions

Several novel chiral bifunctional l-thiazoline-amide derivatives were simply synthesized from commercially available l-cysteine and l-proline in high yield. These catalysts were subsequently applied to the direct enantioselective aldol reactions of various aldehydes, which are rarely reported in the literature. The products with anti configuration were obtained up to 97% ee and 99% dr when the l-thiazoline-amide derivatives were used. A plausible transition state model was proposed to explain the observed enantio and diastereoselectivities.     

Building carbohydrates on the dioxanone scaffold: stereoselective synthesis of d-glycero-d-manno-2-octulose

The title compound has been synthesized via two proline-catalyzed aldol addition reactions of 2,2-dialkyl-1,3-dioxan-5-ones: the first addition to 1,3-dithiane-2-carboxaldehyde, followed by reduction to the corresponding diol, protection of the OH groups and dithiane hydrolysis afforded a protected d-ribose that was used in the second aldol addition reaction.     

Facile and practical synthesis of a cannabinoid-1 antagonist via regio- and stereoselective ring-opening of an aziridinium ion

A scalable synthetic strategy of a chiral, trisubstituted imidazolidinone (1), a novel cannabinoid-1 antagonist, starting from a commercially available mandelic acid (5) is described. The key step involves a regio- and stereoselective ring-opening of an aziridinium ion by an aniline nucleophile (3). A mechanistic study revealed the insight into rate amplification at a lower temperature for vicinal diamine 12 formation via a aziridinium ion 14. Although most intermediates are not isolable by crystallization due to their intrinsic physical properties (oil or foamy solid), the reported synthesis furnished pure 1 without any chromatography purification throughout the entire synthesis. Employing green chemistry principles, this novel synthesis appears to be highly efficient for the manufacturing of multi-kilogram quantities of an optically-pure active pharmaceutical ingredient.     

Organocatalyzed stereoselective construction of N-formylpiperidines via a Michael-aza-Henry-hemiaminalization reaction cascade

An efficient asymmetric synthesis of N-formylpiperidines via an organocatalytic Michael-aza-Henry-hemiaminalization reaction cascade of an aldehyde, a nitroalkene, and an N-arylideneformamide is reported. The reaction is triggered by diphenylprolinol trimethylsilyl ether and creates two C-C and one C-N bonds leading to the formation of highly enantio-enriched N-formylpiperidines with five contiguous chiral centers in a one-pot operation.     

A total synthesis of (+)-oxybiotin from d-arabinose

A novel ten-step synthesis of (+)-oxybiotin, a biologically active analogue of (+)-biotin, has been achieved starting from d-arabinose.     

Unusual anomeric rearrangement of para-nitrobenzoylxanthate d-glycosides: a new direct stereoselective access to α-thioglycosides from pyranose sugars

A mild and general procedure for the synthesis of α-thioglycosides from glycopyranoses is described. The method involves the treatment of pyranose reductive sugar with sodium hydride, carbon disulfide, and p-nitrobenzoyl chloride, as a key step, to yield p-nitrobenzoyl-α-d-thioglycopyranose intermediates with high stereoselectivity, in a one-pot-two-step process. The interest of the strategy highlights a direct stereoselective access to ether-protected 1-thiol-α-d-glycopyranose derivatives (Gal, Glc, and Man) from pyranoses in the absence of anomeric ‘Lewis acid’ promoters.     

Synthesis of hybrids of d-glucose and d-galactose with 1-deoxynojirimycin analogues using ring-closing metathesis

Four hybrids of azasugars with d-glucose and d-galactose have been synthesized from 3-nitro-2,3-unsaturated-O-glycosides. All the hybrid molecules showed moderate activity against β-galactosidase, the one derived from d-glucose and 1,4-dideoxygulonojirimycin 18, and 26, which is a hybrid of d-glucose and 1,4-dideoxymannohomonojrimycin, showed selectivity toward α-glucosidase and β-galactosidase, respectively.