Sequential one-pot five-component synthesis of tetrazole-based spirotetrahydro-β-carbolines

A one-pot five-component two-step sequential synthesis of tetrazole-based tetrahydrospiro[indene-2,1′-pyrido[3,4-b]indole]-1,3-diones in moderate to good yields is described. The reaction consists of four-component condensation of aromatic aldehydes with tryptamine, trimethylsilyl azide (TMSN₃) and isocyanides, followed by addition of ninhydrin. These reactions presumably proceeded through Ugi-azide/Pictet–Spengler processes, respectively.     

Studies on isocyanides and related compounds. A convenient synthesis of 2,3-disubstituted spiroimidazolones

The four-component condensation between cycloketones 1 , ammonium formate, and isocyanides 2 afforded formamides 3 , which were dehydrated to the corresponding isocyanides 4 . Upon treatment with n-butyllithium, compounds 4 cyclized to spiroimidazolones 6 , via the carbanions 5 . A series of 2,3-disubstituted spiroimidazolones 8 was obtained by reacting 5 with aldehydes 7 .     

Designing a sequential Ugi/Ullmann type reaction for the synthesis of indolo[1,2-a]quinoxalinones catalyzed by CuI/l-proline

An efficient strategy for the one-pot syntheses of indolo[1,2-a]quinoxalinones catalyzed by CuI have been developed. The procedures combine the Ugi four-component reaction of aldehydes, 2-iodoaniline, 2-indole carboxylic acid, and isocyanides followed by the copper-catalyzed intramolecular N-arylation of the Ugi product in one-pot procedure, which afford the desired products in good to very good yields.     

Isocyanide-based four-component synthesis of 1,3-indandionylamidinium betaines

An efficient approach for the synthesis of novel 1,3-indandionylamidinium betaines via four-component reaction of 1,3-indandione, aldehydes, amines, and isocyanides, without assistance of any catalyst and under mild reaction conditions has been reported. The structures of these compounds were confirmed by IR, mass spectroscopic, ¹H NMR, ¹³C NMR, and single-crystal X-ray diffraction studies.     

A novel one-pot synthesis of highly diverse indole scaffolds by the Ugi/Heck reaction

A novel one-pot two-step multi component reaction of acrylic aldehydes, bromoanilines, acids and isocyanides yielding polysubstituted indoles is described. The reaction is based on the combination of an Ugi four-component reaction followed by an intramolecular Heck-reaction. The simultaneous use of formic acid and cinnamaldehydes affords in situ generation of 1H-indoles. Convertible isocyanides can also be used with success in this Ugi/Heck strategy and enable synthesis of 1H-indole-2-carboxylic acid building blocks.     

The site of radical attack at the furan ring from MNDO calculations

The semi-empirical SCF MNDO method has been used to calculate the radical reactivities for each reaction site in some neutral furan molecules as the average of the HOMO and LUMO probabilities both in 2p_z atomic orbitals 1

1 SCF: Self-consistent field; MNDO: modified neglect of differential overlap; HOMO: highest occupied molecular orbital; LUMO: lowest unoccupied molecular orbital.

. The carbon atoms C⁵ and C² of of the furan ring are the most favoured sites except for the furan derivatives holding a double bond in the substituent group. Also the SOMO 2

2 SOMO: Single occupied molecular orbital.

probabilities of the radicals formed by addition of a hydrogen atom or a vinyl acetate model radical were calculated. Thus, once a radical is added to the C⁵ position the resulting radical can be partially localized on the carbon C². Furthermore, the enthalpy of reaction for several radicals was estimated by using the calculated heats of formation of the neutral furan molecules and their radicals. The radical addition to the carbon C ⁵ resulted in the most exothermic reaction in comparison with other reaction sites of the molecule. However, no correlation was found between the calculated enthalpies and the degradative-transfer kinetic constants experimentally determined for the radical polymerization of vinyl acetate in the presence of the furan compounds under study.     

Methods for the Synthesis of μ-Hydrocarbon Transition Metal Complexes without Metal–Metal Bonds

Transition metal complexes in which hydrocarbons serve as σ,σ-, σ,π- or π,π-bound bridging ligands are currently of great interest. This review presents efficient and directed syntheses for such compounds, which often have very aesthetic structures. These reactions are among the most important reaction types in modern organometallic chemistry. They can be a useful aid for the synthesis of tailor-made compounds, for example, for models of catalytic processes and, specifically, for the construction of heterometallic compounds. We will discuss reactions of electrophilic complexes with nucleophilic ones, numerous transformations of (functionalized) hydrocarbons with metal complexes, the currently very topical complexes with bridging acetylide and carbide ligands, and organometallic polymers, which can be expected to have interesting and novel materials properties. Chisholm

1 M. H. Chisholm, Polyhedron 1988 , 7, 757–1077.

has described the importance of these complexes as follows: “Central to the development of polynuclear and cluster chemistry are bridging ligands and central to organometallic chemistry are metal–carbon bonds. Thus bridging ligands hold a pivotal role ins the development of Binuclear and polynuclear organometallic chemistry”.     

Simulation of free radical addition reactions modified by the presence of cobalt macrocycles

Free radical addition reactions in the presence of cobaloximes and related compounds have been modelled. Several mechanisms are presented and similarities with the “persistent radical effect” noted by Daikh and Finke are discussed. Cobaloximes and salophen

1 System. name: N-acetyl-p-aminophenyl salicylate.

derivatives are widely used in organic synthesis to build carbon-carbon bonds, whereas in polymer synthesis they are used as catalytic chain transfer agents in the production of oligomers. This work shows that these reactions are closely related and also demonstrates the influence that an external radical source has on the overall reaction kinetics.     

An efficient one-pot method for the synthesis of novel ferrocene-triamide conjugates via pseudo five-component reaction

A simple and efficient one-pot synthesis of novel ferrocene-triamide conjugates from the reaction of ferrocenecarboxaldehyde with Meldrum’s acid and isocyanides in the presence of NH-containing compounds is described. This transformation proceeds through the creation of two CC bonds, two CN bonds, and one CO bond, leading to three peptide bonds, and presumably occurs via a domino sequence involving Knoevenagel condensation, [1+4] cycloaddition, deacetonation, and aminolysis reactions.     

Novel,Simple, and Efficient Synthesis of 3-(2-(5-(Benzylideneamino)-3-phenyl-1H-pyrazol-1-yl)thiazol-4-yl)-4-hydroxy-6-methyl-2H-pyran-2-one Derivatives via a One-Pot,Four-Component Condensation Reaction

The synthesis of 3-(2-(5-(benzylideneamino)-3-phenyl-1H-pyrazol-1-yl)thiazol-4-yl)-4-hydroxy-6-methyl-2H-pyran-2-one derivatives was achieved through a one-pot, four-component reaction involving condensation of 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one, thiosemicarbazide, phenacylcyanaide, and various aryl aldehydes in dry alcohol and few drops of acetic acid under reflux condition. This four-component reaction has some advantages such as ease of handling, good yields, and easy workup. All structures of newly prepared compounds were confirmed by analytical and spectral data.     

Studies on isocyanides: synthesis of tetrazolyl-isoindolinones via tandem Ugi four-component condensation/intramolecular amidation

The Ugi four-component condensation between methyl o-formylbenzoates 1, anilines 2a-c, isocyanides 3, and trimethylsilyl azide (4) afforded the expected Ugi adducts 5a-d, which were cyclized to the title compounds 6a-d upon treatment with sodium ethoxide in ethanol. Starting from aralkyl- or alkylamines 2d-g the Ugi adducts underwent a spontaneous cyclization to tetrazolyl-isoindolinones 6e-j.     

Quantum semiempirical studies on the formation of aromatic polyamides, 1. Effect of structural parameters of diamines on the polyamidation reaction

A semiempirical quantum-mechanical study of structural and electronic parameters of aromatic diamines was performed using the method AM1. The diamines have been considered as condensation monomers, and the reactivities of both amino groups against acyl chlorides have been computed. The study shows that the amidation reaction is controlled mainly by the global charge on the amino group and, in a much smaller extent, by the frontier orbitals. This behaviour is consistent with the large energy gap between the HOMO 1

1 HOMO: highest occupied molecular orbital.

of the diamine and the LUMO 2

2 LUMO: lowest unoccupied molecular orbital.

of the acyl chloride. It has been found also that the electronic nature of the substituents, affecting the charge of the amino groups, greatly affects the carbons directly joined to these groups. This permits to correlate the reactivities with the calculated charges on these carbons:     

“Isocyanide-less” Ugi/Intramolecular Diels-Alder reaction of 5-hydroxymethylfurfural

The one-pot, three-step, four-component Ugi-IMDAF reaction with 5-hydroxymethylfurfural provides simple access to hydroxymethyl-substituted epoxyisoindolones in a diastereoselective and stereospecific manner. The protocol avoids the transfer or isolation of isocyanides, and the broad scope was illustrated by the synthesis of 22 different compounds bearing various substituents on the heterocyclic core.     

One-pot regioselective synthesis of β-lactams by a tandem Ugi 4CC/SN cyclization

β-Lactam scaffold was fabricated regioselectively by a facile one-pot base-mediated synthesis. The reactions of bromoacetic acid 1, primary amines 2, isocyanides 3, and arylglyoxals 4 produced 2-aroyl-4-oxoazetidine-2-carboxamides 6 in good yields via a one-pot tandem Ugi condensation and intramolecular C-alkylation at room temperature in the presence of Cs₂CO₃.     

Directed Aldol Condensations

The present article describes the discovery of a new procedure for aldol condensations for the preparation of α,β-unsaturated carbonyl compounds

1 G. Wittig, H. Pommer, and W. Stilz, German Patent 1199252 (April 5, 1963), BASF; Chem. Abstr. 63, P 1739c (1965).

. The scope of this process is demonstrated by many examples, including some from the natural products sector; at the same time, however, these examples also mark its limitations. The metalated Schiff's bases may be classified as ambident anions; this also explains acylations on the nitrogen. A comparison of the new directed aldol condensation with the formation of unsaturated carbonyl compounds through olefination via phosphorylids shows that the latter method fails when a ketone is used as the substrate. This is where the described procedure using metalated Schiff's bases proves its value.     

Synthesis of diverse phenylglycine derivatives via transformation of Ugi four-component condensation primary adducts

3-(N-Substituted)amino-4-arylamino-1H-isochromenones (isocoumarins) which can be regarded as the enediamine tautomers of the Ugi four-component condensation primary adducts between 2-formylbenzoic acids, arylamines, and isocyanides undergo a facile ring cleavage with amines to give a series of phenylglycine derivatives. Thus, a synthetically useful post-condensation transformation of Ugi four-component condensation primary adducts is described for the first time.     

Isolierung,Struktur und Synthese des Metaboliten von Azapropazon-dihydrat

The renal excretion of AZAPROPAZONE-DIHYDRATE (X)

1 Handelsname: PROLIXAN®. Hersteller: Siegfried AG, Zofingen.

by humans was investigated. Following oral administration a new substance was detected in the urine besides X by TLC. Both compounds were separated by preparative layer chromatography and shown to be unchanged X and its hydroxylated metabolite VIII. The structure of VIII was established by chemical and spectroscopic methods (IR., NMR.) and confirmed by synthesis (Scheme 1).     

Novel Porphyrinoids for Chemistry and Medicine by Biomimetic Syntheses

In 1926 Hans Fischer and Bruno Walach synthesized the first porphyrins.

1 H. Fischer, B. Walach, Justus Liebigs Ann. Chem. 1926 , 450, 164–181.

Currently more than 1400 new articles concerning the synthesis and uses of porphyrins are published every year.

2 CAS Online search for 1994 .

However, the strong interest in these compounds indicated by this is in sharp contrast to their restricted availability. This is reflected in the current price of up to 500 DM for 5 mg of the most important porphyrins used in research and other applications (see Scheme 3). Biomimetic syntheses offer possibilities for an improved approach to porphyrins. By following the example set by nature it is also possible to obtain novel porphyrinoids which are different from naturally occurring porphyrins. This is exemplified by N,N′-bridged porphyrinogens, which have cage structures, inverted porphyrinoids (N atoms in the outer periphery) and, in particular, porphyrins with expanded systems. Among the family of expanded porphyrins are superarenes with up to 34 π electrons. Their pronounced aromaticity is indicated by ¹H NMR spectra, bond length equivalence, planar structures, and electrophilic substitution. With their strong absorption bands, the strongest of which have ? values of > 1000000, a value which exceeds the absorption intensity of all other organic pigments observed until now, and their ability to act as efficient photosensitizers, the expanded porphyrins open interesting perspectives in the fields of photochemistry and photomedicine.     

Isocyanide-based four-component synthesis of ferrocenyl 1,5-disubstituted tetrazoles

A convenient four-component synthesis of ferrocenyl tetrazoles by the reaction of ferrocenecarboxaldehyde, isocyanides, azidotrimethylsilane and alkyl or aryl amines in CH₂Cl₂ at room temperature is reported.     

Copper-catalyzed four-component synthesis of imidazo[1,2-a]pyridines via sequential reductive amination,condensation, and cyclization

A novel and efficient four-component approach for the synthesis of 2,3-disubstituted imidazo[1,2-a]pyridines is described. The copper-catalyzed reductive amination of 2-bromopyridine by sodium azide followed by sequential condensation and cyclization with aldehydes and isocyanides afforded the corresponding imidazo[1,2-a]pyridines in good yields.