Hans-Georg Henning

Advances in Tetramic Acid Chemistry

Publisher Summary The derivatives of tetramic acid are found in a number of natural substances. One example is tenuazonic acid 3 that was isolated from a culture filtrate of Alternaria tenius . Much work on the isolation of tenauzonic acid from plant is now being reported, owing to its interesting pharmaceutical properties. For this reason, numerous partial and total syntheses are described for tenuazonic acid in this chapter, as well as for the more complex tetramic acid derivatives tirandamycin 4 and streptolydigin 5. Much synthetic work to be reported in the chapter is approached with the goal of providing new biologically effective compounds. The majority of syntheses for tetramic acids described in the literature follows a strategy that is derived from the retrosynthetic analysis of tetramic acid derivatives. The chapter provides an overview of the chemistry of the 3-acyl-4-amino-1,5-dihydro-2-pyrrolones. The C-5 carbon atom of the pyrrolone ring is a stereo center that can be provided by natural derivatives of amino acids.

Stereoselective photocyclization to 2-aminocyclopropanols by photolysis of β-aminoketones and oxidative ring opening to enaminones

Abstract Irradiation of β-aminopropiophenones 1 leads to the formation of 2-aminocyclopropanols 2 which can undergo oxidative ring opening to give enaminones 3. The regioselectivity of cyclopropanol formation of the α-benzyl substituted 1 is determined by the preferred charge transfer interaction between the photoexcited benzoyl chromophore and the amino group. The photocyclizations of the α- or β-substituted 1 proceed stereoselectively. No photoracemization of the pure enantiomers of 1m, independent of the solvent polarity was observed. Aryl or alkyl substituents at the C(3)- or C(2)-ring atom stabilize the cyclopropanol derivatives. The formation of 3 indicates regioselective C(1)–C(2) ring opening of 2 probably by localization of the excitation energy.

Effect of substituents on the T1 energy of trans-stilbenes

Abstract Oxygen-induced singlet—triplet absorption and electrochemiluminescence quenching experiments with substituted stilbenes indicate a small influence of monosubstitution or donor—acceptor disubstitution on the triplet energy. This implies a decrease of the S 1 T 1 energy difference particularly in the case of donor—acceptor substituted stilbenes.

The influence of substituents on the photochemical generation and stability of 2-morpholinocyclopropanols

Abstract By irradiation in oxygen-free ether α- or β-substituted β-morpholinopropiophenones 1a-c form the corresponding cyclopropanols 2 with 1-aryl and 2-morpholino group in a relative cis-configuration in high yields. The photocyclization of pure 1a-c enantiomers proceeds enantioselectively under these conditions. In methanol and presence of oxygen electronically excited 1c-h are converted to enaminones 3c-h via oxidation of intermediate cyclopropanols 2c-h. In the presence of electron-acceptor molecules this reaction apparently follows a SET mechanism.

Photochemie von Aminoketonen, 12. Mitt.: Zum Verhalten rotamerer N-Acylglycinester in der photochemischen Glycin → Prolin-Umwandlung

SummaryThe rate of the diastereoselective generation of methyl 3r,2t-N-acyl-3-hydroxy-3-phenyl-prolinates5 from n,π*-excited methyl N-acyl-N-(β-benzoylethyl)-glycinates4 depends on the height of the barrier ΔGc≠ of amide rotation in the educts. Exclusively that rotamer cyclizes, which in the excited state is favoured sterically and by assistance of the amide or ester group for the transfer of the δ-H radical. The progress of the proline formation is determined by the rate of reproducing the favoured rotamer by the isomerization of the unfavoured.

[2+2]-Photocycloaddition von Cyclohexen an 2-Acetyl-5,5-dimethyl-1,3-cyclohexandion und 3-Acetyl-1,5,5-trimethyl-2,4-pyrrolidindion

SummaryIrradiation of solutions of excess cyclohexene and 2-acetyl-5,5-dimethyl-1,3-cyclohexanedione (1), and 3-acetyl-1,5,5-trimethyl-2,4-pyrrolidinedione (4) results mainly in the formation of 1,5-diones2 and5. These originate from intermediate cycloadducts of cyclohexene and theexo-enols of the cyclic 1,3-diketones. The yields decrease with increasing polarity of the solvent. In solution2 and5 are in equilibrium with the cyclic hemiacetales3 and6.

Reactions of cyclic 1,3-dicarbonyl compounds with 1,2(1,4)-dihydro-1-methyl-2(4)-methylene-N-heterocycles. A new access to 6,12-methano-dibenz[d,g]-[1,3]oxazocinones

SummaryThe enamine-type methylene-N-heterocycles1–5 react with cyclic 2-ethoxymethylene-1,3-dicarbonyl compounds6 to give 2-[2-(hetarylidene)ethylidene]-1,3-dicarbonyl compounds7–14. The result of the reactions between 1,2-dihydro-1-methyl-2-methylene-quinoline (1a) and cyclic 1,3-dicarbonyl compounds depends on the nature of the dihydro intermediatesA/B. Dehydrogenation of keton intermediatesA results in 2-(1,2-dimethyl-4(1H)-quinolylidene)-1,3-dicarbonyl compounds17–21. Enol intermediatesB with 6-membered dicarbonyl ring form 6,12-methano-dibenz-[d,g][1,3]oxazocinones22–25.1H NMR spectra and X-ray structure analysis prove the structure of23.ZusammenfassungAufgrund ihres Enamincharakters reagieren die Methylen-N-heterocyclen1–5 mit cyclischen 2-Ethoxymethylen-1,3-dicarbonylverbindungen6 zu den 2-[2-(Hetaryliden)ethyliden]-1,3-dicarbonylverbindungen7–14. Das Ergebnis der Reaktionen zwischen 1,2-Dihydro-1-methyl-2-methylen-chinolin (1a) und cyclischen 1,3-Dicarbonylverbindungen hängt von der Natur der zwischenzeitlich entstehenden DihydroverbindungenA/B ab. Die Intermediat-KetoneA gehen durch Dehydrierung während der Reaktion in die 2-(1,2-Dimethyl-4(1H)chinolyliden)-1,3-dicarbonylverbindungen17–21 über. Die Intermediat-EnoleB mit sechsgliedrigem Dicarbonylring bilden in intramolekularer Reaktion die 6,12-Methano-dibenz[d,g][1,3]oxazocinone22–25, deren Struktur am Beispiel der Verbindung23 durch1H-NMR sowie durch Röntgenkristallstrukturanalyse bewiesen wird.

Heterocyclensynthesen mit 5-Phenyl-isoxazoliumsalzen, 3. Mitt.: Synthese von Pyrrolo[1,2-a]chinazolin-5-onen

Refluxing of ethanol-acetic acid solutions of N-aroyl-N-methyl-benzoylacetamides3 causes elimination of acetophenone and generation of N(1)-substituted N(3)-methyl-1H,3H-quinazoline-2,4-diones5. In contrast, at room temperature in acetanhydride3 eliminate water yielding 2-benzoylmethylene-quinazolinones4, which at 60 °C cyclize to pyrrolo[1,2-a] quinazolin-5-ones6. The transformation4 →6 may be explained in terms of a “normal”Knorr reaction. A “anomalous”Knorr reaction was observed in the case of the more rigid4 d leading to a mixture of diasteromere7 dcis and7 dtrans in kinetically controlled reaction. Favoured by intramolecular hydrogen bonding7 dcis converts to the thermodynamically more stable6 d by warming of the ethanolic solution for 3 hours.