Stereoselective Synthesis of trans-Olefins by the Copper-Mediated S(N)2' Reaction of Vinyl Oxazines with Grignard Reagents. Asymmetric Synthesis of D-threo-Sphingosines

The S_N2′ reaction of 6-vinyl-5,6-dihydro-4H-[1,3]oxazines with Grignard reagents in the presence of CuCN was studied, and high trans selectivity for the formation of double bond was observed with a variety of RMgX. The S_N2′ reaction, coupled with regioselective asymmetric aminohydroxylation reaction, provided a highly efficient route for the asymmetric synthesis of d-threo-N-acetylsphingosine.     

A new convergent and stereoselective synthesis of 2,5-disubstituted N-acylpyrrolidines

A new synthesis of 2,5-disubstituted N-acylpyrrolidines through an S_N2′ reaction promoted by the nitrogen anion of a secondary amide onto an allylic bromide is reported. A moderate stereoselectivity, in favour of the trans heterocycle, was observed during the cyclization of a chiral precursor, while a good stereoselectivity, this time in favour of the cis one, was obtained when the second stereocentre was introduced after the cyclization step to give the same product.     

Highly regio- and stereocontrolled brominations of gem-difluorinated vinyloxiranes

gem-Difluorinated vinyloxiranes, which are useful synthetic intermediates for difluorinated compounds, were brominated regio- and stereoselectively. Introduction of bromide at the allylic epoxide carbon with inversion of stereochemistry was realized by MgBr₂·Et₂O to furnish an anti vic-bromohydrine, whereas the reaction with LiBr/AcOH afforded the other diastereomer selectively. Moreover, both reactions at high temperature allowed to obtain, the thermodynamically favored products, E-allylic alcohols dominantly.     

Synthesis and metal-ion binding properties of new N2S4- and N2S5-donor macrocycles

Synthetic procedures for new N₂S₄- and N₂S₅-donor macrocycles (2 and 4) were given. The ligands were prepared by the reaction of NaBH₄ with the appropriate macrocyclic diamide in the presence of boron trifluoride ethyl etherate in dry tetrahydrofuran (THF). Solvent extraction method was used to evaluate metal-ion binding properties of the new ligands. The solvent extraction experiments suggested that the reduced macrocycles have Ag⁺ and Hg²⁺ selectivities compared to Pb²⁺, Co²⁺, Zn²⁺, Ni²⁺, Cu²⁺, Mn²⁺ and Cd²⁺ ions. The extraction constants (log K _ex) and complex compositions were determined for Ag⁺ and Hg²⁺ complex of compound (4).     

Highly regio- and stereocontrolled SN2′ reactions of gem-difluorinated vinyloxiranes with monoalkylcopper reagents

Reaction of gem-difluorinated vinyloxiranes with RCu(X)Li allowed us to introduce the R group regioselectively at the fluorine-attached terminal carbon atom in an S_N2′ manner to afford (E)-allylic alcohols exclusively, while homoallylic alcohols with anti stereochemical relationship were found to be obtained selectively from higher-ordered cuprates derived from CuCl and RMgBr in a ratio of 1:3.     

Interesting transformations of naturally occurring cassane diterpenoids and bioevaluation of the products

Two cassane diterpenoids, pulcharrin G (1) and 6β-cinnamoyl-7β-hydroxy-voucapen-5-α-ol (2), the constituents of Caesalpinia pulcherrima, were treated with BF₃·OEt₂ to furnish two olefinic products 3 and 4, respectively. The products were formed by elimination of water and migration of a methyl group from C-4 to C-5. The cytotoxic and antimicrobial activities of 3 and 4 were examined.     

Complex formation equilibria between Ag(I) and thioureas in n-propanol

Complex formation equilibria between Ag(I) and thiourea or N-alkyl-substituted thioureas have been investigated in n-propanol by potentiometry at 10 °C intervals from 5 to 50 °C. Stepwise formation of tris-coordinated AgL_n (n = 1-3) complexes has been found for the majority of the ligands. ΔH and ΔS values for the complex formation reactions have been evaluated from the dependence of ln β_n on temperature. The alkyl-substituents affect the ligand affinities in different ways in relation with the coordination level n.The reactions are exothermic with few exceptions. Enthalpy favoured complex formation with negative dependence of ΔG on temperature (ΔS > 0) have been found.The enthalpy and entropy changes for the stepwise complex formation equilibria are correlated by two linear compensative relationships with the same isoequilibrium temperature 50-51 °C.     

The allylic nucleophilic substitution of Morita-Baylis-Hillman acetates with isocyanides: a facile synthesis of trisubstituted olefins

Morita-Baylis-Hillman acetates undergo smooth allylic nucleophilic substitution (S_N2′) with tosylmethyl isocyanide (TosMIC) in the presence of a catalytic amount of BF₃·OEt₂ under mild conditions to furnish trisubstituted olefins in high yields with (E)-stereoselectivity.     

Sulfoxide-controlled SN2′ displacements between cuprates and vinyl and alkynyl epoxy sulfoxides

The S_N2′ displacement of readily available vinyl epoxy sulfoxides with organocopper reagents takes place in good yields with high anti selectivity and a good degree of E/Z stereocontrol to produce enantiopure α-hydroxy vinyl sulfoxides. A second allylic displacement on the related mesyloxy vinyl sulfoxides allows for the asymmetric construction of two adjacent chiral centers. In addition, cuprate mediated S_N2′ addition to alkynyl epoxy sulfoxides affords α-hydroxy allenyl sulfoxides in good yields.     

Indium-mediated alkynylation of Baylis-Hillman acetates: a novel route to 1,4-enynes

Baylis-Hillman acetates undergo smooth alkynylation with aryl-susbstituted iodoalkynes in the presence of indium metal in refluxing dichloromethane to furnish 1,4-enynes in high yields with (E)-stereoselectivity. In the absence of Lewis acid, the reaction follows both S_N2 and S_N2′ pathways affording 1:1 mixtures of 1,4-enynes. Upon addition of 10 mol % of InBr₃, the reaction proceeds preferably in the S_N2′ manner. In the case of adducts derived from acrylonitrile, the corresponding products are obtained in fairly good yields and with (Z)-stereoselectivity.     

Concise synthesis of trans- and cis-3,4-disubstituted piperidines based on regio- and stereoselective allylation of cyclopentenyl esters

3,4-Disubstituted piperidines were synthesized through anti S_N2′ allylation of 4-substituted 2-cyclopentenyl esters with reagents based on RMgX and CuX, thus allowing equal access to both trans- and cis-isomers. As an application, the paroxetine intermediate was synthesized efficiently. During the investigation, the MeOCH₂CO₂ group was found to show high reactivity in the pivotal anti S_N2′ type reaction using the reagent derived from (i-PrO)Me₂SiCH₂MgCl and CuCN.     

An efficient oxidation of 2-aryl-1,2,3,4-tetrahydro-4-quinolones employing ferric chloride hexahydrate-methanol: synthesis of naturally occurring 4-alkoxy-2-arylquinolines

A simple, inexpensive and efficient oxidation of 2-aryl-1,2,3,4-tetrahydro-4-quinolones has been carried out by employing FeCl₃·6H₂O-methanol under mild conditions. This method has been investigated for the synthesis of an endothelin receptor antagonist, benzofuro[3,2-b]pyridine core structure.     

Sequential alkylation/cyclization/isomerization of ethyl 3-(o-trifluoroacetamidoaryl)-1-propargylic esters: a new route to 2-acyl- and 2-ethoxycarbonyl-3-alkenyl indoles

The reaction of ethyl 3-(o-trifluoroacetamidoaryl)-1-propargylic esters with ethyl iodoacetate or α-bromoacetophenone in the presence of K₂CO₃ in DMSO provides a new simple access to 2-acyl- and 2-ethoxycarbonyl-3-alkenyl indoles.     

Regio- and stereoselective reactions between cyclic Baylis-Hillman type adducts and N-nucleophiles and P-nucleophile

New important organic compounds multifunctionalized cyclic 6-membered and 7-membered allylic amines, azide and phosphonates have been obtained via regio- and diastereoselective reactions of cyclic Baylis-Hillman type adducts 1 with N-nucleophiles and P-nucleophile. We have found that the reactions proceed by S_N2 or S_N2′ processes exclusively, or by both processes simultaneously. The S_N2′ process occurs with anti stereochemistry.     

Dithionite adducts of pyridinium salts: regioselectivity of formation and mechanisms of decomposition

¹H and ¹³C NMR spectroscopy has been used to detect and to characterize the adducts formed, in alkaline solutions, by the attack of dithionite anion on 3-carbamoyl or 3-cyano substituted pyridinium salts. In all studied cases, only 1,4-dihydropyridine-4-sulfinates, formed by attack of dithionite oxyanion on the carbon 4 of pyridinium ring, were found. This absolute regioselectivity seems to suggest a very specific interaction between the pyridinium cation and the dithionite through the formation of a rigidly oriented ion pair, determining the position of attack. In weak alkaline solution, the adducts decompose according to two mechanisms S_Ni and S_Ni′: the S_Ni path is operative in all studied cases and preserves the 1,4-dihydro structure yielding the corresponding 1,4-dihydropyridines, whereas the S_Ni′ path involves the shift of 2,3 or 5,6 double bonds yielding 1,2- or 1,6-dihydropyridines, respectively. The formation of 1,2- or 1,6-dihydropyridines, in addition to 1,4-dihydro isomers, depends on their respective thermodynamic stabilities.     

Efficient construction of bicyclic systems by an internal SN2′ enolate alkylation/ring-closing metathesis (RCM) strategy: a concise synthesis of the trans-hydrindane nucleus

A concise and efficient synthesis of the trans-hydrindane system has been achieved by a novel intramolecular S_N2′ enolate alkylation/ring-closing metathesis (RCM) strategy with a good degree of stereocontrol.     

Synthesis of substituted 3-methylene-2-pyridones from Baylis-Hillman derivatives and its application for the generation of 2-pyridone substituted spiroisoxazolines

The synthesis of substituted 3-methylene-2-pyridones via S_N2 displacement reaction of nucleophiles bearing a keto group on the acetyl derivative of Baylis-Hillman adducts of acrylonitrile followed by TFA/H₂SO₄-mediated intramolecular cyclization is described. The utility of these pyridone derivatives for the synthesis of new spiroisoxazolines in highly regio- and stereo-selective fashion is also illustrated. The structure of the spiroisoxazolines has been secured via X-ray crystallographic analysis.     

Efficient and Convenient Protocol for the Synthesis of 3,5-Disubstituted 1,2,4-Oxadiazoles Using HClO4-SiO2 as a Heterogeneous Recyclable Catalyst

Silica-supported perchloric acid (HClO₄-SiO₂) was found to be a new, highly efficient, inexpensive, and reusable catalyst for a rapid and efficient synthesis of various 1,2,4-oxadiazoles with good to excellent yields under solvent-free conditions. The present methodology has been effectively utilized for the synthesis of oxolamine, an anti-inflammatory drug.     

Synthesis of a solvent-sensitive highly fluorescent derivative of perfluorocyclopentene

A solvent-sensitive highly fluorescent compound, N-[2-(1′,3′,4′,4′,5′,5′-hexafluorocyclopentenyl)]-4-(5-methoxy-thiazolyl)pyridine (1D) was synthesized as an unexpected product of the reaction of 4-bromo-5-methoxy-2-(4-pyridyl)thiazole (1B) with perfluorocyclopentene in the presence of n-BuLi. Primary mechanism of this reaction was proposed, and the photophysical properties of 1D in different solvents were studied.     

Vibrational frequencies and force constants of N2O4 in complexes with molecules of different solvents determined by Raman spectra andAb initio calculation

The Raman spectra of N₂O₄ solutions in organic solvents have been recorded. The frequencies ofv ₁,v ₂, andv ₃ bands of N₂O₄ increase with increasing solvent electron-donor properties. Especially large changes ofv ₃ N-N stretching band have been observed (254.5 cm^–1 in n-hexane, 276.5 cm^–1 in 1,4-dioxane). The ab initio calculations have shown that the interaction between N₂O₄ and electron-donor molecules causes an increase of N-N and N-O stretching and O-N-O bending force constants of N₂O₄ in agreement with the results of Raman study.