A novel access to disubstituted acetylenes

Reactions of organometallic reagents with 1-(substituted ethynyl)-1H-1,2,3-benzotriazoles 5 derived from a variety of benzotriazolylmethyl ketones 3 afforded disubstituted acetylenes in synthetically useful yields.     

Copper-catalyzed multicomponent reaction: facile access to novel phosphorus amidines

The synthesis of a novel class of phosphorus amidines via a copper-catalyzed multicomponent reaction of sulfonyl azides, alkynes and iminophosphoranes is described. The protocol is efficient and general.     

Green access to novel spiro pyranopyrazole derivatives

A catalyst-free multicomponent reaction (MCR) capable of affording a wide range of novel spiro pyranopyrazole derivatives from pyrazolone in situ formed from acetylenic esters with hydrazine hydrate at room temperature with isatin and malononitrile is reported. A plausible mechanism is suggested. Catalyst-free conditions along with green solvent system make the process ecofriendly as well as economical. Simple reaction conditions and easy work-up procedure that resulted into simple isolation and purification of products by non-chromatographic methods, that is, by simple recrystallization from methanol as well as novelty are the significant advantages of the present protocol.     

A novel 3,4-dihydroisoquinoline annulation: expedient access to isoquinoline heterocycles

3,4-Dihydroisoquinoline carboxylate 1 undergoes a smooth annulation with ω-bromopropionate, butyrate or ortho-bromomethyl benzoate 2 to afford the isoquinoline heterocycle 3 upon treatment with potassium tert-butoxide in DMF at −60 °C. This novel annulation constitutes a formal direct synthesis of cyclic Reissert equivalent compounds, thus offers an expedient access towards certain medicinally important isoquinoline heterocycles and relevant natural alkaloids, that is, of berberine and erythrina types.     

Fluorination in superacids: a novel access to biologically active compounds

In HF-SbF₅, reaction of various alkaloids with NBS, NCS, H₂O₂ yields fluoroderivatives: anti-addition is observed at the C6C7 double bond with tabersonine, but a more complex reaction is operative with vindoline, leading to 7-substituted (Br, Cl, OH)-20-fluoro derivatives. A completely different reaction pathway is observed with bis indole alkaloids (vinblastine, anhydrovinblastine, vinorelbine) in HF-SbF₅. In the presence of NBS (or better of CCl₄ or CHCl₃), 20′,20′-difluoroderivatives are obtained. Vinflunine (20′,20′-difluoro-3′,4′-dihydrovinorelbine) has been selected for its promising antitumor activity.     

Asymmetric Michael reaction: novel efficient access to chiral β-ketophosphonates

The asymmetric Michael reaction between chiral β-enaminophosphonates derived from (S)-1-phenylethylamine and various electrophilic alkenes furnished β,β-disubstituted ketophosphonates in good yields and with excellent enantioselectivity.     

Stille/Diels-Alder reaction sequences: diversity-oriented access to novel steroids

[reaction: see text] An efficient, diversity-oriented approach to novel steroid analogues possessing a C-5beta configuration begins with the Stille cross-coupling of enantiomerically pure cycloalkenylstannane trans-2 and enol triflate 3. The resulting diene trans-4 engages in Diels-Alder cycloaddition reactions with a range of dienophiles to give, after removal of protecting groups, biologically interesting 6,7-disubstituted steroid analogues.     

Intramolecular cyclization of alkoxyaminosugars: access to novel glycosidase inhibitor families

We report the synthesis of two novel families of iminosugars as glycosidase inhibitors involving an intramolecular cyclization between an N-alkoxyamino group and a latent aldehyde of a reducing sugar as the key step. Using this methodology we have prepared the hitherto unknown bicyclic polyhydroxylated N-(methoxy, benzyloxy)anhydroazepanes and N-benzyloxy-d-xylonojirimycin; all these novel compounds turned out to be moderate β-glucosidase inhibitors in a pH-dependent manner.     

Anhydrodihydroartemisinin and its 10-trifluoromethyl analogue: access to novel d-ring-contracted artemisinin trifluoromethyl ketones

The preparation of the 10-trifluoromethyl hydroartemisinin, followed by dehydration, afforded the trifluoromethyl analogue 2 of anhydrodihydroartemisinin 1. The reactivity of these two glycals of artemisinin were compared in epoxidation and halogenation reactions. Iodination of glycal 1 in water and the further rearrangement of the produced iodo hemiacetal provided the new D-ring-contracted aldehyde 8alpha, where the methyl at C-9 is beta. Epoxidation of 10-trifluoromethyl anhydrodihydroartemisinin 2 stereoselectively provided the beta-epoxy ether 11 in high yield. When treated with hexafluoro-2-propanol or trifluoroethanol, 11 readily underwent a rearrangement yielding to the D-ring-contracted trifluoromethyl ketone 9alpha with retention of configuration at C-9.     

Synthesis and reactivity of N-sugar-maleimides: an access to novel highly substituted enantiopure pyrazolines

Two diastereomeric isoxazolines were synthesized in a stereoselective manner with 6.64–20.36% diastereoisomeric excess. The cycloaddition of N-sugar-maleimide in the presence of MgBr₂ afforded isoxazolines with high diasterioselectivities (76–84% de). The 1,3-dipolar cycloaddition reaction was diastereospecific and enantiomerically pure (3R,4S,5S,6S,3aR,6aS)-pyrazolines were obtained from N-sugar-maleimides via 1,3-proton migration.     

General access to a novel class of silyl heterocycles

2-Trimethylsilyl-substituted five-membered heterocycles can be accessed through the reaction of bromo(methoxy)methyltrimethylsilane with 1,2-dithiols, 1,2-mercapto alcohols, 1,2-mercapto amines, and 1,2-hydroxy amines, leading to the formation of several 2-silylated 1,3-dithiolanes,-oxathiolanes,-thiazolidines, and-oxazolidines. Dedicated to Prof. Edmunds Lukevics on the occasion of his 70th birthday __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1838–1844, December, 2006.     

A novel access to 3-aryl-2-norbornyl cation

A novel access to a 2-norbornyl cation under mild, non acidic conditions is found in the addition of photochemically generated 4-dimethylaminophenyl cation to 2-norbornene. Deprotonation to nortricyclene or nucleophile addition ensue depending on the solvent characteristics.     

Simple access to novel β-hydroxy-β-trifluoromethyl imines

Selected imines reacted with three different trifluoromethyl group-containing ketones in a non-catalyzed manner at ambient temperature to give the corresponding β-hydroxy-β-trifluoromethyl imines in good to excellent yields. With 1,1,1-trifluoroacetone a 1:1 and a 2:1 reaction product was obtained. The reduction of 2-isopropylimino-4-phenyl-5,5,5-trifluoropentan-4-ol led to a 5:1 diastereomeric mixture of the corresponding amine, whose dominant form was found to be (2S, 4R) 4-isopropylamino-4-phenyl-2-trifluoromethyl-butan-2-ol in the solid state. Hydrolysis in one case gave the respective β-hydroxy ketone.     

A novel heterobifunctional linker for facile access to bioconjugates

A convenient synthesis of a novel heterobifunctional linker molecule is described. The linker contains a thiol-reactive nitropyridyl disulfide group (Npys) and an aldehyde-reactive aminooxy group with a propensity to form disulfide and oxime linkages. The utility of the linker molecule to cross-link different biomolecules has been demonstrated by employing it in the efficient preparation of a peptide-oligonucleotide conjugate. The linker reported herein could be a useful tool for cross-coupling of different but appropriately functionalised biomolecules.     

The reaction of decaborane with hydrazoic acid: A novel access to azaboranes

The reaction of B₁₀H₁₂(SMe₂)₂ ( 1 ) with HN₃ yields arachno-B₁₀H₁₂(N₃)(NH₂) ( 2 ), a product with a μ-NH₂ group. Compound 2 can be hydrolysed to give the known arachno-B₉H₁₃(NH₃) ( 3 ). nido-NB₉H₁₁(N₃) ( 4 ) is formed from 2 by a deprotonation/protonation sequence. The azaborane nido-NB₁₀H₁₃ ( 5 ) is a product of the thermolysis of 2 . The structures of 2–5 are elucidated by 2-D COSY ¹¹B–¹¹B NMR spectra; the structure of 2 is also elucidated by an X-ray structure analysis.     

Formation and reactivity of novel pyranosidic nicholas oxocarbenium ions: access to C-ketosides and branched-chain C-ketosides

[Structure: see text] Dicobalt hexacarbonyl propargyl complexes, prepared from alkynyl ketoses, display an unexpected reactivity when treated with Lewis acids in the presence of nucleophiles and furnish C-ketosides, branched-chain C-ketosides, or branched-chain C-glycals depending on the nucleophile and the carbohydrate starting material.     

An efficient access to novel enantiomerically pure steroidal delta-amino acids

A highly chemoselective sequence of Stille and Heck couplings on the heterocyclic bromoenol triflates 2 a-c with the bicycloalkenylstannanes cis-3 and trans-3 furnished the intermediate bromobutadienes 4 a-c in good yields ranging from 73-94 %. A modified Heck coupling protocol employing the palladacycle 8 and an additional bidentate ligand such as 1,4-bis(diphenylphosphinyl)butane allowed a significant reduction in catalyst loading while still obtaining the heterocyclic 1,3,5-hexatrienes 5 a-c in good yields (71-94 %). The unsymmetrically substituted 1,3,5-hexatrienes 5 a-c in solution underwent 6pi-electrocyclizations following an optimized microwave-heating protocol to yield the steroidal tetracycles cis-7 a-c and trans-7 b (59-69 %). Tetracycles cis-7 a-c are the products of a subsequent 1,5-hydrogen shift to the thermodynamically more stable, more highly substituted diene units. Removal of the tert-butyl groups provided the novel steroidal delta-amino acid 9 a and the delta-amino acid derivatives 9 b, c in good yields (76-86 %).     

A novel and concise synthetic access to chiral 2-substituted-4-piperidone

A novel and concise synthetic access to enantiopure chiral 2-aryl/alkyl substituted 4-piperidone has been demonstrated.This new route features two key steps:the highly diastereoselective conjugate addition of homochiral lithium amides to trans-β-substituted-α,β-unsaturated methyl esters guaranteed the enantiopurity at 2 position(de19:1)and the intramolecular attacking of carbanions to methyl esters led to the formation of the piperidone ring.A wide range of substrates,including chiral2-aryl and 2-alkyl-4-piperidones,were successfully synthesized with modest to high yield.Moreover,some non-chiral3-substituted-4-piperidones were also synthesized with enhanced ring-formation yield,implicating the versatility of this method in construction of various piperidine rings.     

Photochemical generation of radical anions. An access to novel structures

The preparation of the radical anions of tetrabenzocyclooctatetraene (TBCOT) and fluorene (FLH) by photochemical methods leads to the observation of novel structures.     

Tetradecanuclear polycarbonatolanthanoid clusters: Diverse coordination modes of carbonate providing access to novel core geometries

The synthesis of two high nuclearity lanthanoid clusters demonstrates the versatility of the carbonate anion as a robust cluster forming agent, potentially allowing for the formation of otherwise inaccessible core topologies. The complexes, [Gd(14)(CO(3))(13)(ccnm)(9)(OH)(H(2)O)(6)(phen)(13)(NO(3))](CO(3))(2.5)·(phen)(0.5) () and [Dy(14)(CO(3))(13)(ccnm)(10)(OH)(H(2)O)(6)(phen)(13)](CO(3))(2.5)·(phen)(0.5) () (ccnm = carbamoylcyanonitrosomethanide, phen = 1,10-phenanthroline), contain a [Ln(14)(CO(3))(13)(OH)] core in which the carbonate anions display four unique coordination modes. The complexes are chiral, and the ccnm ligands also display four unique coordination modes. Extensive intra- and intermolecular π-π stacking between phen ligands leads to the formation of 1D chains in the crystal structure. Both complexes display magnetic properties that are indicative of antiferromagnetic coupling, with complex displaying behaviour consistent with possible single molecule magnet properties.