Substitution effects in intramolecular aziridine-allylsilane cyclizations

We report here the synthesis of an aziridine tethered to a substituted allylsilane via a substituted tether. These tether-substituted aziridine-allylsilanes cyclize differently upon treatment with BF₃·OEt₂ than tether-unsubstituted aziridine-allylsilanes and provide a 6-endo-type product. We show that steric interactions between the N-substituent of the aziridine and substitution on the tether can control the product distribution.     

Cu0-catalysed 1,3-dipolar cycloadditions of α-amino acid derived N,N-cyclic azomethine imines to ynones

A series of 20 CuAIAC reactions between eight 4-acylamino substituted pyrazolidine-3-one-1-azomethine imines and four terminal ynones were performed using Cu⁰ as catalyst. The corresponding fluorescent cycloadducts were obtained in very high yields upon simple workup. Thus, Cu-metal turned out to be a better catalyst than Cu^I in terms of yield and ease of isolation. Availability of azomethine imines, mild reaction conditions, and simple workup enable a “click” access to libraries of densely substituted 2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-ones. Reactivity of differently substituted dipoles was evaluated experimentally and by quantum chemical methods (DFT).     

4-Indolylbutanals from rhodium-catalyzed hydroformylation of allylindoles as precursors of benzofused indolizines

New 4-indolylbutanals have been prepared via a rhodium-catalyzed hydroformylation of differently substituted N-allylindoles. The aldehydes bearing an electron-donating group on the indole nucleus 3-position can evolve into benzofused indolizines via a one pot intramolecular cyclodehydration.     

Synthesis of perfragilin A, B and some analogues

Synthesis of the cytotoxic isoquinoline quinone perfragilin A, an improved synthesis of perfragilin B and preparation of some analogues of both these compounds are described. Cytotoxicity evaluation of a number of the products is reported. The regioselectivity in Diels-Alder reactions of differently substituted benzoquinones with 2-aza-1,3-bis(t-butyldimethylsilyloxy)-1,3-butadiene is described.     

Palladium mediated cycloisomerization of sugar alkynols: synthesis of cyclic enol-ethers and spiroketals

Functionalized bicyclic enol-ethers and spiroketals are prepared by Pd catalyzed cycloisomerization of 3-C-alkynylfuranosyl derivatives. Cycloisomerization of differently substituted alkyne derivatives revealed a preference for 6-endo-dig cyclization over 5-exo-dig if the substituent is not sufficiently electron withdrawing. The scope of these cycloisomerizations has been further extended by integrating with conjugate addition.     

Nickel-catalyzed, base-mediated amination/hydroamination reaction sequence for a modular synthesis of indoles

A catalytic system consisting of [Ni(cod)₂] and ligand dppf enabled an efficient synthesis of differently substituted indoles through a modular reaction sequence, which consists of intermolecular aminations and intramolecular hydroaminations with ortho-alkynylhaloarenes.     

Synthesis, electrochemical and photochromic behaviour of a series of (1,4-dithiafulven-6-yl)substituted 3H-naphtho[2,1-b]pyran derivatives

The synthesis and electrochemical and photochromic properties of new 3,3-diphenyl-8-(1,4-dithiafulven-6-yl)-[3H]-naphtho[2,1-b]pyran derivatives containing differently substituted dithiafulvenyl units are described. An example of electrochemical dimerization is shown which gives access to electroactive bichromophoric systems. Such systems could allow the study of the interplay of photochromic and electrochemical properties.     

Manganese-catalyzed cross-coupling reactions of aliphatic amines with aryl halides

An efficient and convenient protocol has been developed for the N-arylation of aliphatic amines with differently substituted aryl halides using a MnCl₂·4H₂O/l-proline catalyst and NaOt-Bu as the base in DMSO.     

Imidazo[1,5-a]pyridine-3-ylidenes—pyridine derived N-heterocyclic carbene ligands

The ready synthesis of differently substituted 2H-imidazo[1,5-a]pyridin-4-ium bromides is reported. These salts are precursors for a new class of N-heterocyclic carbene ligands. As a consequence of their bicyclic geometry, these ligands are capable of influencing the coordination sphere of a carbene bound metal. The usefulness of these ligands was demonstrated in the palladium-catalyzed Suzuki-Miyaura cross-coupling of sterically hindered aryl chlorides.     

Functionalized dihydropyridines do reduce alkoxycarbene complexes of chromium and give access to polycyclic butenolides

The dihydropyridine-induced reduction of alkoxycarbene complexes of chromium has been generalized to differently substituted dihydropyridines, e.g. N-benzyl dihydropyridine and N-methyl-N’N’-diethyldihydronicotinamide. In all the cases examined, alkoxyalkynyl carbene complexes lead, upon cascade insertions, to butenolides, the diastereomeric excesses being dependent on the structure of the dihydropyridines.     

Pd(II)-catalyzed intramolecular C–H activation/C–C cross coupling for the synthesis of carbazoles from diaryl acetamides

Pd(II)-catalyzed intramolecular C–H activation/C–C cross coupling within N,N-diphenyl-acetamides allows the efficient formation of differently substituted carbazoles. In this cross-dehydrogenative coupling, many different functional groups are tolerated and the starting material N,N-diphenyl-acetamides can be easily prepared in one step from commercially available acetanilides and iodobenzenes.     

Palladium-catalyzed amination and cyclization to heteroannellated indoles and carbazoles

New ortho-bromodiarylamines in the benzo[b]thiophene series were prepared by palladium-catalyzed amination, either in the benzene or in the thiophene ring. These were submitted to palladium-catalyzed cyclization, under different required conditions, to give several differently substituted thieno[3,2-c] or [2,3-b]carbazoles and indolo[3,2-b]benzo[b]thiophenes. This constitutes a novel synthetic route to both tetracyclic systems.     

The asymmetric synthesis of β-lactams: HETPHOX/Cu(I) mediated synthesis via the Kinugasa reaction

The reactions of nitrones with terminal alkynes, catalysed by a range of HETPHOX ligands afforded β-lactams in moderate to good conversions with ees up to 55%. High levels of diastereoselectivity, dependent on the alkyne, were obtained. For example, the reaction is highly cis-diastereoselective with phenylacetylene (>9:1), while an unexpected reversal of diastereoselectivity is observed with the 3,5-trifluoromethyl phenylacetylene, which is highly trans selective (1:9) with an ee of 53%. The reaction scope with differently substituted nitrones and phenylacetylenes was also studied.     

Cautions regarding the physical interpretation of statistically based separation of the ortho substituent effect into inductive,mesomeric, and steric components—II : Acid catalysed esterification of benzoic acids by methanol and cyclohexanol

In order to attain a better insight into the composition of Taft E_s^o, constants the rate data of hydrion catalysed esterification of both m,p-substituted and o-substiluted benzoic acids by cyclohexanol and methanol were submitted to a statistical analysis using inductive mesomeric and steric substituent constants and various dummy variables differently structured. Furthermore a principal component analysis with subsequent identification of the first principal component via multiple regression analysis was applied. It has been demonstrated that in the reactions of m,p substituted compounds some substituents capable of exerting strong mesomeric effects show peculiar characteristics deviating from the general trend. Since the same result was obtained in the correlations of ortho substituted benzoic acids this effect was taken into account using an appropriate dummy variable which in all cases improved the multiple coefficient of determination. It is concluded that the esterification rates of the ortho substituted compounds depend essentially upon inductive and steric effects (taken away OMe OEt and NO₂) as proposed by Taft. While generally the E_s^o values may be regarded as some measure of a steric effect, this is not true for the methoxy and ethoxy groups.     

Studying competitive lithiations at alpha-, ortho-, and benzylic positions in various N-protected aniline derivatives

The directing effects of the t-BuOCONH- (NHBoc) and the t-BuCONH- (NH-pivaloyl) groups have been investigated on a series of differently substituted anilines. Depending on the nature of the directing group and the substrate, lithiation either occurred in the ortho-, benzylic-, or alpha-position. In general, it was observed that ortho-lithiation is the least facile process and alpha-lithiation slightly favored compared to lithiation in the benzylic position. However, it was found that minor changes in the starting materials led to different regioselectivity in the metalation process. For example, changing substituents from methyl to ethyl can result in completely different regioselectivity. As final conclusion, a graphical guideline for lithiation experiments is presented.     

Efficient synthesis and solid state analysis of 3-(1H-pyrrol-2-yl)quinoxalin-2(1H)-one and 2-(1H-pyrrol-2-yl)-1H-benzo[d]imidazole from pyrrolo-2-ylglyoxyl acid

The synthesis of new pyrrole-functionalized quinoxalines and benzimidazole is described. Our methodology involves the condensation between 2-oxo-2-(1H-pyrrol-2-yl)acetic acid and differently substituted 1,2-phenylene diamines. Depending on the substitution and on the reaction conditions, the synthesis leads to either the pyrrolyl-quinoxaline or -benzimidazole heterocycles. Further insights concerning the structural arrangement of the pyrrolyl-quinoxaline were obtained by solid state analysis, revealing an inverted pyrrole similar to that observed for 2,3-dipyrrolyl quinoxalines. This observation accounts for the fact that strong dipolar interactions or intermolecular H-bonds may govern the structural arrangement in the solid state.     

Stereoselective synthesis of constrained norbornane-derived spiro-β-lactams

New enantiopure polycyclic norbornane-derived spiro-β-lactams were synthesized by means of a Staudinger ketene–imine reaction between unsymmetrical bicyclic chiral ketenes, generated from differently substituted norbornane carboxylic acids, and (E)-N-benzyl-N-(phenylmethylene)amine, with high yields and moderate to good stereoselectivities. The diastereoisomeric results were rationalized taking into account the increasing steric encumbrance present on the norbornane skeleton and the stability of the products. The configurations of the newly formed stereocenters of spiro-β-lactams were assigned on the basis of 2D NMR experiments and X-ray analysis. Spiro-β-lactams were subjected to acid hydrolysis obtaining the corresponding norbornane-derived β-amino acids.     

Dispersion-corrected energy barriers for silylene addition to white phosphorus, a density functional investigation into substituent effects

A density functional investigation into differently substituted silylenes with respect to the first step in the addition to white phosphorus is presented. The investigations include dispersion corrections in the density functional treatment. They become sizable for the transition state geometries for the silylenes as they become increasingly substituted by bulky groups. Hence, dispersion corrections are essential for a quantum chemical treatment of real molecules using density functional theory. The different singlet–triplet energy separations of differently substituted silylenes were also investigated and compared with calculated activation barriers for the first step in the addition reaction.     

Kinetik der Bromierung von Phenolen und phenolischen Mekrkernverbindungen

The bromination of 15 dinuclear phenolic compounds (dihydroxydiphenylmethanes, methylene bisphenols) by molecular bromine in acetic acid was studied kinetically at 22°C. In all compounds the electrophilic substitution occurred inortho-position to the phenolic hydroxy group of the methyl phenol unit while the non reacting neighboring unit was differently substituted by H, CH₃,t-Bu and NO₂. A decrease in the reaction rate was observed in 2,2′-dihydroxydiphenylmethanes, where the +M-effect of the hydroxy group is diminished by an intramolecular hydrogen bond. The strength of this hydrogen bond may be influenced mainly by steric factors. Strong electron withdrawing substituents like NO₂ show a rate decreasing influence on the reactivity of the neighboring unit also in 2,4′- and 4,4′-dihydroxydiphenylmethanes.