Conversion of 4-hydroxy-2-cyclopentenone derivatives into valuable fine chemicals

This thesis deals with the synthesis of valuable chemicals starting from renewable resources. All syntheses start from 4-hydroxy-2-cyclopentenone and its derivatives, which can be readily obtained from furfural, made from agricultural waste like bran or bagasse, via a straightforward reaction sequence. Reduction of furfural yields furfuryl alcohol, which is then efficiently converted to 4-hydroxy-2-cyclopentenone via a Piancatelli rearrangement in a microreactor. Therefore, 4-hydroxy-2-cyclopentenone and its derivatives represent the key building blocks used in this thesis. In the first chapter, various substituted 2-pyrones were synthesized from 4-hydroxy-2-cyclopentenone and its derivatives, utilizing the thermal rearrangement of cyclopentadienone epoxides to 2-pyrone as the key step.It was possible to obtain unsubstituted 2-pyrone via a short reaction sequence in multigram scale with high yield and purity. Using a similar reaction sequence allowed the synthesis of naturally occurring 6-substituted alkyl 2-pyrones 2 in excellent yields. Additionally, 4-hydroxy-2-cyclopentenone could be converted into various 6-substituted α-hydroxyalkyl 2-pyrones via a Baylis Hillman reaction with different aldehydes. The so obtained compounds bearing a α-hydroxyalkyl side chain allowed a plethora of transformations. The enzymatic resolution provided access to enantiomerically pure 2-pyrones. Alternatively, elimination of the α-hydroxy group gave access to naturally occurring Sibirinone and related natural products. Oxidation of the α-hydroxy group yielded the corresponding carbonyl compounds, which was used for the synthesis of naturally occurring Gibepyrone F after introducing a methyl substituent in 3-position. Using a different strategy, the synthesis for 5-substituted 2-pyrones yielded a mixture of 3- and 5-substituted 2-pyrones, which could be explained by a [1,5] sigmatropic H-shift. The second chapter deals with the sustainable oxidation of 4-hydroxy-2-cyclopentenone to dione, which was used for the synthesis of enol esters. Investigation of the reactivity of these enol esters revealed that they undergo an interesting rearrangement when subjected to FVT. The resulting γ-alkylidenebutenolides are highly interesting new compounds with high functional group density. After an intensive study of the reaction and its conditions, a plausible mechanism for the rearrangement was proposed. Additionally, a broad scope of esters was synthesized and rearranged to the corresponding γ-alkylidenebutenolides. The γ-alkylidenebutenolides were obtained in an E/Z mixture, which was separable by chromatography in about 30% combined yield.The final chapter concentrates on the ruthenium-catalyzed redox isomerization of different 4-hydroxy-2-cyclopentenones to 1,3-cyclopentanedione derivatives in water. These diketone derivatives are highly valuable compounds for the synthesis of various complex organic molecules and not many protocols are reported for their synthesis. The redox isomerization proved to be suitable for unsubstituted 4-hydroxy-2-cyclopentenone and for derivatives with a substitution in 5-position giving the corresponding diketones in up to 91% yield. However, the reaction proved to be dependent on the steric bulk of the substituent as smaller substituents gave the best results for the isomerization. In conclusion, an efficient synthetic strategy for various valuable compounds was developed, namely 2-pyrones, γ-alkylidenebutenolides and 1,3-cyclopentanedione derivatives. All compounds could be obtained from the same starting materials, 4-hydroxy-2-cyclopentenone and its derivatives, which are readily available from renewable resources. This underlines that 4-hydroxy-2-cyclopentenones are useful and reliable platform chemicals for fine chemical synthesis