Dieter E. Kaufmann

2-(Het)aryl-Substituted 7-Azabicyclo[2.2.1]heptane Systems

Epibatidine (1) is a recently discovered trace alkaloid found in the skin of a Latin-Amencan poisonous frog. Its remarkably high analgetic activity is accompanied by high toxicity. Therefore, in order to tune its biological activity, a convergent and efficient synthetic pathway was sought to synthesize epibatidine derivatives with different (het)aryl substituents. The hydro(het)arylation of the key intermediate 7-azabicycloheptene (10) represents such an approach. The synthesis of 10 by a Diels-Alder reaction of an N-activated pyrrole (7) with ethynyl p-tolyl sulfone (6) and subsequent steps has been optimized. The crucial last step, the reductive cleavage of the vinyl sulfone 9, has been replaced by a high-yield fluoride-induced degradation of the s-silylated sulfone 12 to give 10. A number of structurally different racemic epibatidine analogs (16b-e) can be prepared by palladium-catalyzed hydro(het)arylation of 10 with iodo(het)arenes 15b-e in good yields.

Epibatidine Alkaloid Chemistry: 5. Domino-Heck Reactions of Azabicyclic and Tricyclic Systems †

Palladium-catalyzed hydroarylations and additional domino reactions of aza-bicyclic and tricyclic norbornene derivatives were investigated and a series of new epibatidine analogues were synthesized.

Suzuki Coupling of Chiral 1,1′‐Binaphthyl Systems − New Synthetic Routes to Functionalize the 2‐ and 2,2′‐Positions

1,1′-Binaphthyl derivatives 1-5, substituted in the 2- or 2,2′-positions are used in palladium-catalyzed Suzuki coupling reactions. The mono- and bis-borylated coupling components 2, 4 and 5 can easily be prepared and purified, are air-stable and are therefore interesting starting materials for Suzuki coupling reactions with several aryl halides. Thus a variety of new axially-chiral 2- and 2,2′-arylated 1,1′-binaphthyls can be synthesized. Selective monoarylation of 3, 4 and 5 can be performed. Subsequent and stepwise arylation offers general access to unsymmetrically substituted binaphthyls. Moreover, interesting atropisomeric complex molecules, such as 4,4′-bis[2-(1,1′-binaphthyl)]-1,1′-biphenyl (18a), are accessible. Compounds of type 18, which can be obtained by twofold Pd-catalyzed coupling reactions, are of high potential value as ligands or promoters in catalytic, asymmetric processes or as chiral precursor molecules for host-guest interactions.

Chemistry of polyhalogenated nitrobutadienes, 8: Nitropolychlorobutadienes—Precursors for insecticidal neonicotinoids

Nitropolychlorobutadienes are valuable precursors for highly functionalized acyclic or (hetero)cyclic compounds. In this 8th part of our synthetically oriented series we focus on the application of these versatile starting materials in the synthesis of analogs of the heterocyclic insecticides imidacloprid and thiacloprid, and the acyclic counterpart clothianidin. In addition to the main synthetic part, leading to imidazolidines or oxazolidines, further promising types of compounds derived by subsequent chemical modifications, are introduced. Most of the new compounds show high insecticidal activity.

The Hydroarylation Reaction—Scope and Limitations

The synthetic potential of stereoselective, palladium-catalyzed hydro(het)arylation reactions of bi-, tri- and tetracyclic (hetero)alkenes in the presence of phospines and arsines as highly efficient ligands was studied. The mechanism of this reductive Heck reaction becomes more complex in the case of benzonorbornenes. Hydroarylation of diazabicyclo-[2.2.1]heptenes provides a stereoselective access to aryldiaminocyclopentanes. Electron-deficient arylpalladium complexes shift the reaction towards the product of a formal 1,2-hydrazidoarylation reaction of 1,3-cyclopentadiene by a stereoselective C-N cleavage. Due to steric reasons, rigid bicyclo[2.2.2]octenes react slower in hydroarylation reactions than the corresponding bicyclo[2.2.1]heptenes. The more flexible bicyclo[4.2.2]decene system already tends to undergo domino-Heck reactions, even under reductive conditions. When a tetracyclic cis-allylcyclopropane is carbopalladated in the presence of formates, the neighboring cyclopropane ring is attacked in the first reported example of a π,σ domino-Heck reaction.

Chemical improvement of surfaces: Part 1: Novel functional modification of wood with covalently bound organoboron compounds

Abstract A novel type of chemical modification of wood was developed and applied to functionalise wood permanently with organoboron compounds. The covalent attachment of metalloid substituents via a benzotriazolyl-activated benzoic acid to wood hydroxy groups was in focus. Thus, standard modification procedures in wood chemistry – such as the acetylation – are improved by avoiding either the loss of half the reagent in the case of acid anhydrides or the release of corrosive hydrochloric acid in the case of carboxylic acid chlorides. The introduced boron moiety could be a contribution to solve a long-lasting problem in the field of wood protection: chemical fixation of an organoboron compound by means of a well-defined covalent bond. Accordingly, the hitherto insufficient long-term availability of conventionally spread boron compounds as wood protecting agents caused by leaching can now be avoided. The investigation was also extended to arylsilyl compounds, as a second type of organometal substances, which potentially allow for subsequent chemical modifications by ipso-substitution. The presented wood modification reactions yielded weight percent gain values from 14% to 31% on beech wood, spruce wood, and pine sapwood meal (approximately 500 μm in diameter) or pine sapwood veneer chips. The modified meals and chips were analysed by IR spectroscopy.

A DFT Study on the Mechanism of the Annulation Reaction of Trichloronitroethylene with Aniline in the Synthesis of Quinoxalinone-N-oxides

The new annulation reaction of trichloronitroethylene with aniline results in the formation of a quinoxalinone-N-oxide derivative. The mechanism of this one-pot annulation reaction between trichloronitroethylene (TCNiE) and anilines has been extensively investigated with B3LYP/6-31+G** methodology. Five different paths (1-5) were proposed and modeled by using this method. These paths were compared in terms of the activation energies of their rate-determining steps and in regard to the experimental findings. Paths 3 and 5, proceeding via four-membered heterocyclic rings, were found to be the most plausible paths with activation energies of 32 and 29 kcal/mol for the rate-determining steps, respectively. The effects of substituent, solvent, temperature, and computational method on these steps were also investigated. The results showed that path 5 is the most plausible mechanism for the annulation reaction of trichloronitroethylene with aniline.

Chemistry of polyhalogenated nitrobutadienes, 10: Synthesis of highly functionalized heterocycles with a rigid 6-amino-3-azabicyclo[3.1.0]hexane moiety

Summary The nitropolychlorobutadienes 3, 4 are valuable building blocks for various amination and successive heterocyclization products. Nucleophilic substitution reactions of the partially protected, bioactive amines 1, 2 with either vinyl, imidoyl or carbonyl chlorides result in the formation of the enamines 11, 12, 13, 16, 25, the amidine 6, and the amides 20, 21, respectively. In the following, cyclization to the highly functionalized pyrazoles 27, 28, pyrimidine 26 and pyridopyrimidine 24 succeeded. Deprotection of 21, 12 and 28 proved to be only partially feasible.

Chemical improvement of surfaces. Part 2: Permanent hydrophobization of wood by covalently bonded fluoroorganyl substituents

Abstract A recently developed esterification method in our laboratory was applied to permanent hydrophobization of wood surfaces. Specifically, the covalent attachment of fluoroorganyl substituents to wood hydroxy groups via benzotriazolyl-activated, substituted benzoic acids was in focus. Weight percent gain values from 10% to 28% were obtained on Scots pine (Pinus sylvestris) sapwood veneer chips. It proved feasible to lower the temperature for wood modification from 150°C to 120°C, or even to 70°C so that thermal decomposition of wood during modification can be neglected. The modified chips were analyzed by attenuated total reflection – infrared and X-ray photoelectron spectroscopy. Covalent attachment of the fluorobenzoic acids led to a very high, permanent hydrophobicity of the wood surface, documented by outstanding contact angles of up to 143°.

Reductive Heck Reactions of N-Methyl-substituted Tricyclic Imides

The palladium-catalyzed hydroarylation of N-methyl-substituted tricyclic imides was studied in order to find a new stereoselective access to a series of new exo-aryl(hetaryl)-substituted tricyclic N-methylimides.