Asymmetric Synthesis of 2-Aryl-5-oxotetrahydrofuran-2-carboxylic Acids

Abstract

A s y m m e t r i c S y n t h e s i s o f 2 -A r y l -5 -o x o t e t r a h y d r o f u r a n -2 -c a r b o x y l i c A c i d sAbstract: 3-Aryl-2-hydroxycyclopent-2-en-1-ones, when subjected to asymmetric oxidation, result in enantiomerically enriched 2-aryl-5-oxotetrahydrofuran-2-carboxylic acids. Electron-donating substituents in the para position of the phenyl ring increase the yield and decrease the enantioselectivity of the process.Various substituted tertiary lactones are valuable precursors for bioactive compounds. 1 On the other hand, these structures themselves bear different biological activities; 2 for example, the derivatives of the title compound -2-aryl-5-oxotetrahydrofuran-2-carboxylic acids -exhibit depressive action on the central nervous system. 3There are limited methods for the synthesis of 2-aryl-5-oxotetrahydrofuran-2-carboxylic acids. 3,4 No convenient methods for the asymmetric synthesis of these compounds have been described. The aim of the present study was to elaborate a method for the asymmetric synthesis of 2-aryl-5-oxotetrahydrofuran-2-carboxylic acids from achiral 3-aryl-2-hydroxycyclopent-2-en-1-ones.We have recently developed a short and highly enantioselective method for the synthesis of 2-alkyl-substituted 2-hydroxyglutaric acid g-lactones from 3-alkylcyclopentane-1,2-diones by asymmetric oxidation using the Ti(Oi-Pr) 4 /diethyl tartrate/t-BuOOH complex. 5 We expected that achiral 3-aryl-2-hydroxycyclopent-2-en-1-ones 1 (enol tautomers of 3-arylcyclopentane-1,2-diones) might also be substrates for the asymmetric oxidation complex and afford 2-aryl-5-oxotetrahydrofuran-2-carboxylic acids 2 (Scheme 1).For the synthesis of the starting compounds, aryl-substituted cyclopentane-1,2-diones, we used the coupling of benzaldehydes with 1-acetoxybut-3-en-2-one (6) (according to the Stetter reaction 6 ), followed by an intramolecular base-induced cyclization. Thus, 3-aryl-2-hydroxycyclopent-2-en-1-ones 1a-d were prepared from the corresponding benzaldehydes 7a-d and 1-acetoxybut-3-en-2-one (6) [prepared in a 53% yield from but-2-yne-1,4-diacetate (5) 7 ] (Scheme 2).In order to find appropriate asymmetric oxidation conditions, the reaction was carried out with 1a (X = H) as a model compound at different molar ratios of 1a, Ti(Oi-Pr) 4 , (+)-diethyl tartrate and t-BuOOH. The results obtained are presented in Table 1.According to the data obtained, unsubstituted 2-hydroxy-3-phenyl-2-cyclopenten-1-one (1a) gets oxidized like alkyl-substituted substrates -the main isolated reaction product (after lactonization) was lactone acid 2a. In all of the cases, the yield of the lactone acid was lower (32-43%) than that for alkyl substituted substrates (up to 83%). 5 Also, the enantioselectivity of the asymmetric oxidation was considerably lower than that for alkyl-substituted substrates (ee ≥95%). The best yield (43%, ee 78%) was obtained at the molar ratio of 1.0:1.0:1.6:2.5 of the components of the 1a and Ti complex when a dilute reaction mixture was used (Table 1, entry 4). The best enantioselectivi...