(−)-Sparteine-Mediated Asymmetric Cyclocarbolithiation of Alkenes Combined with a Stereospecific retro-[1,4]-Brook Rearrangement

A novel domino-type reaction sequence consisting of an enantioselective intramolecular carbolithiation of 6-phenylhex-5-enyl carbamates and a highly stereospecific retro-[1,4]-Brook rearrangement is reported. The carbocycles are formed with high enantiomeric (er >98 : 2) and diastereoisomer ratios (dr >99 : 1) in good yields (47 – 60%). On the basis of the absolute configuration of the cyclization products, a stereoretentive mechanism is proposed for the retro-[1,4]-Brook rearrangement.     

Solid-State Photocyclodimerization of 1-Thiocoumarin (= 2H-1-Benzothiopyran-2-one)

Irradiation (λ > 390 nm) of 2H-1-benzothiopyran-2-one ( 1 ) in the solid state affords selectively 6aα,6bα,12bα,12cα -tetrahydrocyclobuta[1,2-c:4,3-c′]bis[1]benzothiopyran -6,7-dione ( 2 ), the head-to-head (HH) cis-cisoid-cis-dimer, while irradiation of 1 in the solid state using shorter wavelengths (λ > 340 nm) affords a mixture of all four cis-fused tricyclic dimers 2 – 5 . These results represent a novel wavelength effect in solid-state photochemistry.     

1,5-Stereocontrol in reactions of 2,4-disubstituted alk-2-enylstannanes with aldehydes; an approach to the stereoselective synthesis of branched triols

2-(tert-Butyldimethylsilyloxymethyl)-4-(methoxymethoxy)pent-2-enyl(tributyl)stannane is transmetallated by tin(IV) chloride stereoselectively to give a pent-1-en-3-yltin trichloride that reacts with aldehydes with excellent (E)-1,5-syn-stereocontrol, e.g. (3E)-1,5-syn-3-(tert-butyldimethylsilyloxymethyl)-5-(methoxymethoxy)-1-phenylhex-3-en-1-ol was the dominant product with benzaldehyde. The products from these reactions were taken through to more complex 2-substituted alk-2-enyl(tributyl)stannanes but only very low yields of the expected products were obtained from tin(IV) chloride mediated reactions of these stannanes and aldehydes. Nevertheless a stereoselective synthesis of 2-substituted 4-[(E)-2-alkoxypropylidene]tetrahydrofurans was developed.     

Methyl and Phenylmethyl 2-Acetyl-3-{[2-(dimethylamino)-1-(methoxycarbonyl)ethenyl]amino}prop-2-enoate in the Synthesis of heterocyclic systems: Preparation of 3-amino-4H-pyrido-[1,2-a]pyrimidin-4-ones

Methyl 2-acetyl-3-{[2-(dimethylamino)-1-(methoxycarbonyl)ethenyl]amino}prop-2-enoate ( 4 ) and phenyl-methyl 2-acetyl-3-{[2-(dimethylamino)-1(methoxycarbonyl)ethenyl]amino}prop-2-enoate ( 5 ) were prepared in three steps from the corresponding acetoacetic esters, and used as reagents for the preparation of N³-protected 3-amino-4H-pyrido[1,2-a]pyrimidin-4-ones 10 – 12 , 5H-thiazolo[3,2-a]pyrimidin-5-one 13 , 4H-pyrido[1,2-a]-pyridin-4-one 19 and 2H-1-benzopyran-2-ones 20 – 23 . Free 3-amino-4H-pyrido[1,2-a]pyrimidin-4-ones 24 – 26 were prepared from 10 – 12 by removal of the 2-(methoxycarbonyl)-3-oxobut-1-enyl or 3-oxo-2-[(phenyl-methoxy)carbonyl]but-1-envl as N-protecting group by various methods.     

Alkylation of Imidazolidinone Dipeptide Derivatives: Preparation of Enantiomerically Pure Di- and Tripeptides by ‘Chirality Transfer’ via a Pivalaldehyde N,N-Acetal Center. Preliminary Communication

Glycylglycine, glycyl-(S)-alanine, and (S)-alanylglycine esters are cyclized through pivalaldehyde imines to give dipeptide-derived 3-(benzyloxycarbonyl)-2-(tert-butyl)-5-oxoimidazolidine-1-acetates 1 – 3 . These are alkylated diastereoselectively by Li-enolate formation and addition of alkyl bromides or iodides (products 4 – 6 ). Starting from (S)-alanine and glycine, (S)-alanyl-(S)-alanine or (R)-alanyl-(R)-alanine, and (R)-alanyl-(R)alanyl-(S)-alanine- have thus been prepared, with the (tert-butyl)-substituted N,N-acetal center playing the role of a pivot or lever for diastereoselective formation of new stereogenic centers under kinetic or thermodynamic control.     

Enantioselective Preparation of γ-Amino Acids and γ-Lactams from Nitro Olefins and Carboxylic Acids,with the Valine-Derived 4-Isopropyl-5,5-diphenyl-1,3-oxazolidin-2-one as an Auxiliary

Titanium enolates of acyl-oxazolidinones 1 , derived from acetic, propanoic, 3-methylbutanoic, and 4-methylpentanoic acids and 4-isopropyl-5,5-diphenyl-1,3-oxazolidin-2-one, are added to aliphatic and aromatic nitro olefins in the presence of TiCl₄ (Schemes 2 – 4). The products, 4-nitro carboxylic-acid derivatives 2 , are formed in high diastereoselectivities (ds 80 to >99%) and in good yields (50 – 75% of purified samples of ds >98%). Hydrogenation over Raney-Ni of the NO₂ group in the adducts leads directly to the corresponding γ-lactams ( 3 and 8 ; 80 – 92%), with recovery of the insoluble auxiliary (ca. 95%). Ring opening is achieved through the N-Boc-lactams ( 4 ), which are converted to N-Boc-protected γ-amino acids 5 or to their benzyl and methyl esters ( 6 and 7 ; Scheme 5). The configuration of the products (containing up to three new stereogenic centers; Scheme 1) is assigned by comparison with literature data, by X-ray crystal-structure analysis (for 2c , g , f , 8 , Fig.), and by analogy. Thus, the (S)-auxiliary gives rise to combination of the trigonal centers of enolate and nitro olefin with Si/Si topicity (relative topicity all-lk; cf. A ).     

Formation of Cyclic Ketals from Hydroxyalkyl Enol Ethers,a stereoelectronically controlled endo-trig-cyclization process

Acid-catalyzed cyclic ketal formation vs. hydrolysis of a series of hydroxyalkyl cyclic enol ethers in the presence of 1 equiv. of H₂O, and acid-catalyzed cyclic-ketal formation (same ketals as above) vs. methanolysis of a series of mixed pent-4-enyl hydroxyalkyl ketals with N-bromosuccinimide in the presence of 4 equiv. of MeOH led to the same result: the intramolecular cyclization processes occur at similar rates as the intermolecular H₂O or MeOH attacks independently of the size of the rings formed (five-, six-, or seven-membered), by cyclizations. These results can be explained by the facts that, due to stereoelectronic effects which impose a torsional strain to the sp² hybridized O-atom, the cyclization activation enthalpy decreases, as the length of the hydroxyalkyl chain increase (ease of cyclization: 7 > 6 > 5), whereas the entropy factor favors the cyclization in the reverse fashion (ease of cyclization: 5 > 6 > 7). The various reaction pathways have been examined using the semi-empirical Hamiltonian AM1, and the results obtained confirm that large-ring formation is enthalpically much favored over the cyclization processes leading to small rings (ease of cyclization: 7 > 6 > 5).     

Synthesis of Novel 1,3,5-Trisubstituted Pyrazoles as Potential Hypoglycemic Agents

A novel series of 1,3,5-trisubstituted pyrazoles was synthesized. Thus, ethyl 2,4-dioxo-6-phenylhex-5-enoate (I) was condensed with phenylhydrazine to afford 3-ethoxycarbonyl-1-phenyl-5-styrylpyrazole (II) which on fusion with hydrazine hydrate gave the corresponding acid hydrazide (III). Reaction of III with the appropriate isothiocyanate yielded the disubstituted thiosemicarbazides (IVa-e) which were cyclized into thiotriazoles (Va-e), thiadiazoles (Vla-e) and oxadiazoles (VIIa-). The structure of the newly synthesized compounds was elucidated by elemental analyses, IR and ¹H NMR spectra.     

Electrochemical Intramolecular Aminooxygenation of Unactivated Alkenes

An electrochemical approach to the intramolecular aminooxygenation of unactivated alkenes has been developed. This process is based on the addition of nitrogen‐centered radicals, generated through electrochemical oxidation, to alkenes followed by trapping of the cyclized radical intermediate with 2,2,6,6‐tetramethylpiperidine‐N‐oxyl radical (TEMPO). Difunctionalization of a variety of alkenes with easily available carbamates/amides and TEMPO affords aminooxygenation products in high yields and with excellent trans selectivity for cyclic systems (d.r. up to>20:1). The approach provides a much‐needed complementary route to existing cis‐selective methods.     

Imidazo[2,1-b]thiazole carbamates and acylureas as potential insect control agents

Imidazo[2,1-b]thiazole carbamates and acylureas were prepared by reaction of 5-hydroxymethylimidazo-[2,1-b]thiazole and imidazo[2,1-b]thiazole-5-carboxyamide with arylisocyanates. The products formed depend from the substituent bonded at the 6 position of the imidazothiazole moiety, and from the reaction conditions.     

Oxidation of N-acyl-2-(cycloalk-1-enyl)anilines with ozone and hydrogen peroxide

Treatment of the ozonization products from N-acetyl- or 2-methyl-N-trifluoroacetyl-6-(cyclopent-1-enyl)anilines with NaBH₄ gives 6-methyl-2-tetrahydropyranylaniline. When treated with Me₂S, the ozonization products yield the corresponding oxoaldehyde dimethyl acetals. The oxidation of N-acetyl-2-(cyclopent-1-enyl)- or -(cyclohex-1-enyl)anilines with H₂O₂ in HCOOH affords -(2-acetamidophenyl)-5-oxopentanoic or -6-oxohexanoic acid, respectively. The reaction of N-acetyl-2-(cyclopent-1-enyl)aniline with H₂O₂ in the presence of Na₂WO₄ and H₃PO₄ gives 3,1-benzooxazine in high yield.     

Synthesis of Condensed and Uncondensed Tetrazolo[1,5-<Emphasis Type="Italic">b</Emphasis>][1,2,4]triazines as Potential Antimicrobial Agents

Summary. Reactions of two cyclic amidrazones, the 6-methyl and 6-phenyl derivatives of 7-hydrazinotetrazolo[1,5-b][1,2,4]triazines with mono- and dicarbonyl compounds afforded various heterocyclic systems. Thus, acetic acid, benzoyl chloride, or ethyl chloroformate reacted with the former cyclic amidrazones to yield the corresponding [1,2,4]triazolo[4,3-d]tetrazolo[1,5-b][1,2,4]triazines. With pyruvic acid or ethyl pyruvate the corresponding hydrazone derivatives were obtained, which then cyclized to tetrazolo[1′,5′:2,3][1,2,4]triazino[5,4-c][1,2,4]triazines. The 9,10-dioxotetrazolo-triazinotriazine structures were synthesized by condensative cyclization of the cyclic amidrazones with diethyl oxalate, whereas the reaction of these amidrazones with acetylacetone or ethyl acetoacetate furnished pyrazolyltetrazolo[1,5-b][1,2,4]triazines through the isolable hydrazone intermediates. Some of the representative members of the prepared compounds were screened for antimicrobial activity.     

Synthesis of substituted 3-amino-4-cyano-1-oxo-1,2,5,10-tetrahydroazepino [3,4-b]indoles

The preparation of 3-amino- and 3-dialkylamino-4-cyanoazepino[3,4-fc]indoles bearing substituents on the aromatic nucleus and N¹⁰ is outlined. Starting from suitable substituted ethyl 3-formylindole-2-carboxy-latcs 2 , condensation with malononitrile ( 3 ) and subsequent sodium borohydride-reduction yielded ethyl 3-(2,2-dicyanoethyl)indole-2-carboxylates 5 and 19 , respectively, which were cyclized in boiling alkoxides to 3-alkoxy-4-cyanoazepino[3,4-b]indoles 10,11,20 and 21 . This sequence constitutes a novel and flexible route to functional azepino[3,4-b>]indoles. The aminolysis of 10,11,20 and 21 with different amines and ammonia yielded the title compounds which were screened for their possible biological activity.     

Improved red dopants for organic electroluminescent devices

A t-butyl substituted red fluorescent dye, 4-(dicyanomethylene)-2-t-butyl-6-(1,1,7,7-tetramethyljulolidyl-9-enyl)-4H-pyran (DCJTB), has been found to be an excellent dopant in AIQ₃ which produces a highly efficient organic EL device with improved red chromaticity. Unlike 4-(dicyanomethylene)-2-methyl-6-(1,1,7,7-tetramethyljulolidyl-9-enyl)-4H-pyran (DCJT), DCJTB can be synthesized in a pure form directly from the unsymmetrical 4-(dicyanomethylene)-2-(t-butyl)-6-methyl-4H-pyran without the contamination of the non-fluorescent bis-condensation byproduct which is prevalent in the DCJT preparation. Both photoluminescence and electroluminescence in the solid films of DCJTB in AlQ₃ are modestly enhanced by the extra t-butyl substitution as a result of a reduction in the effect of concentration quenching. The operation stability of the DCJTB doped EL device is superior, having a half-life of over 5,000 h driven at an initial brightness > 400 cd/m².     

Synthesis of Acyclic Aliphatic Amides with Contiguous Stereogenic Centers via Palladium-Catalyzed Enantio-, Chemo- and Diastereoselective Methylene C(sp3)−H arylation

The enantioselective desymmetrizing C−H activation of α-gem-dialkyl acyclic amides remains challenging because the availability of four chemically identical unbiased methylene C(sp³)−H bonds and increased rotational freedoms of the acyclic systems add tremendous difficulties for chemo- and stereocontrol. We have developed a method for the synthesis of acyclic aliphatic amides with α,β-contiguous stereogenic centers via Pd^II-catalyzed asymmetric arylation of unbiased methylene C(sp³)−H, in good yields and with high levels of enantio-, chemo- and diastereoselectivity (up to >99 % ee and >20:1 d.r.). Successive application of this method enables the sequential arylation of the gem-dialkyl groups with two different aryl iodides, giving a range of β-Ar¹-β′-Ar²-aliphatic acyclic amides containing three contiguous stereogenic centers with excellent diastereoselectivity.     

Order of Reactivity of OH/NH Groups of Glucosamine Hydrochloride and N-Acetyl Glucosamine Toward Benzylation Using NaH/BnBr in DMF

The order of reactivity of OH and NH groups of glucosamine hydrochloride (GlcNH₂^.HCl) and N-acetyl glucosamine (GlcNAc) toward benzylation with NaH/BnBr in DMF was investigated. For GlcNH₂^.HCl, benzyl groups were introduced in the order of N-Bn > N-Bn₂ > 1-O-Bn > 6-O-Bn > 4-O-Bn > 3-O-Bn; for GlcNAc, benzyl groups were introduced in the order of 1-O-Bn > 6-O-Bn > 4-O-Bn > 3-O-Bn > N-Bn. A range of partially benzylated 2-N,N′-dibenzyl glucopyranosides and GlcNAc derivatives were obtained in a single step.     

Dual catalytic performance of arene-ruthenium amine complexes for norbornene ring-opening metathesis and methyl methacrylate atom-transfer radical polymerizations

Arene ruthenium(II) complexes bearing the cyclic amines RuCl₂(η⁶-p-cymene)(pyrrolidine)] ( 1 ), [RuCl₂(η⁶-p-cymene)(piperidine)] ( 2 ), and [RuCl₂(η⁶-p-cymene)(peridroazepine)] ( 3 ) were successfully synthesized. Complexes 1 – 3 were fully characterized by means of Fourier transform infrared, UV–visible, and NMR spectroscopy, elemental analysis, cyclic voltammetry, computational methods, and one of the complexes was further studied by single crystal X-ray crystallography. These compounds were evaluated as catalytic precursors for ring-opening metathesis polymerization (ROMP) of norbornene (NBE) and atom-transfer radical polymerization (ATRP) of methyl methacrylate (MMA). NBE polymerization via ROMP was evaluated using complexes 1 – 3 as precatalysts in the presence of ethyl diazoacetate (EDA) under different [NBE]/[EDA]/[Ru] ratios, temperatures (25 and 50°C), and reaction times (5–60 min). The highest yields of polyNBE were obtained with [NBE]/[EDA]/[Ru] = 5000/28/1 for 60 min at 50°C. MMA polymerization via ATRP was conducted using 1 – 3 as catalysts in the presence of ethyl-α-bromoisobutyrate (EBiB) as initiator. The catalytic tests were evaluated as a function of the reaction time using the initial molar ratio of [MMA]/[EBiB]/[Ru] = 1000/2/1 at 95°C. The increase in molecular weight as function of time indicates that complexes 1–3 were able to mediate the MMA polymerization with an acceptable rate and some level of control. Differences in the rate of polymerization were observed in the order 3 > 2 > 1 for the ROMP and ATRP.     

Strong Ligand Stabilization Based on π-Extension in a Series of Ruthenium Terpyridine Water Oxidation Catalysts

The substitution behavior of the monodentate Cl ligand of a series of ruthenium(II) terpyridine complexes (terpyridine (tpy)=2,2′:6′,2′′-terpyridine) has been investigated. ¹H NMR kinetic experiments of the dissociation of the chloro ligand in D₂O for the complexes [Ru(tpy)(bpy)Cl]Cl ( 1 , bpy=2,2’-bipyridine) and [Ru(tpy)(dppz)Cl]Cl ( 2 , dppz=dipyrido[3,2-a:2′,3′-c]phenazine) as well as the binuclear complex [Ru(bpy)₂(tpphz)Ru(tpy)Cl]Cl₃ ( 3 b , tpphz=tetrapyrido[3,2-a:2′,3′-c:3′′,2′′-h:2′′′,3′′′-j]phenazine) were conducted, showing increased stability of the chloride ligand for compounds 2 and 3 due to the extended π-system. Compounds 1 – 5 ( 4 =[Ru(tbbpy)₂(tpphz)Ru(tpy)Cl](PF₆)₃, 5 =[Ru(bpy)₂(tpphz)Ru(tpy)(C₃H₈OS)/(H₂O)](PF₆)₃, tbbpy=4,4′-di-tert-butyl-2,2′-bipyridine) are tested for their ability to run water oxidation catalysis (WOC) using cerium(IV) as sacrificial oxidant. The WOC experiments suggest that the stability of monodentate (chloride) ligand strongly correlates to catalytic performance, which follows the trend 1 > 2 > 5 ≥ 3 > 4 . This is also substantiated by quantum chemical calculations, which indicate a stronger binding for the chloride ligand based on the extended π-systems in compounds 2 and 3 . Additionally, a theoretical model of the mechanism of the oxygen evolution of compounds 1 and 2 is presented; this suggests no differences in the elementary steps of the catalytic cycle within the bpy to the dppz complex, thus suggesting that differences in the catalytic performance are indeed based on ligand stability. Due to the presence of a photosensitizer and a catalytic unit, binuclear complexes 3 and 4 were tested for photocatalytic water oxidation. The bridging ligand architecture, however, inhibits the effective electron-transfer cascade that would allow photocatalysis to run efficiently. The findings of this study can elucidate critical factors in catalyst design.     

Peripherally Hexasulfanylated Subporphyrins

Peripherally hexachlorinated meso‐triphenyl subporphyrin 4 was prepared by chlorination of meso‐triphenyl subporphyrin 1 with N‐chlorosuccinimide and was effectively transformed to hexasulfanylated subporphyrins 5 – 8 via nucleophilic aromatic substitution (S_NAr) reactions with the corresponding thiols under basic conditions. The structures of 5 – 8 have been all well characterized by single‐crystal X‐ray analysis. ¹H NMR studies indicated that the meso‐phenyl substituents undergo restricted rotation for 5 – 8 , while the β‐sulfanyl substituents are conformationally flexible in 5 , 6 , and 8 , and are strictly regulated to an anti‐conformation in 7 . Judging from the absorption spectra, the oxidation and reduction potentials, and the DFT calculations, the substituent effects decrease in the order of 5 > 6 > 7 > 8 . Subporphyrin 8 effectively captures C₆₀ in a 1:1 manner in [D₈]toluene solution.