Triphenylphosphine promoted addition of acetylenic esters to benzofuran-2,3-dione: one-pot synthesis of Novel γ-Spirolactones

The reaction of the zwitterionic intermediates generated from dialkyl acetylene dicarboxylates and triphenylphosphine with benzofuran-2,3-diones provides a one-pot route to new highly functionalized γ-spirolactones in good yield.


Introduction
The 2,5-dihydrofuran-2-one moiety is an integral part of many natural and unnatural products.2][3][4] For example 2,5-dihydrofuran-2-one derivatives 1 and 2 have antimicrobial activities. 58][9] They offer significant advantages over conventional linear syntheses by reducing time and by saving money, energy, and raw materials, thus providing both economic and environmental benefits.At the same time, diversity can be achieved from building up libraries by simply varying each component.

Results and Discussion
In this type of two-component reaction catalyzed by nucleophiles, triphenylphosphine (Ph3P) has been the most often studied nucleophilic species.As early as 1961, Tebby observed that the addition of Ph3P to various activated alkynes like DMAD, dicyanoacetylene, and dibenzoylacetylene generates zwitterionic intermediates. 21,22he reactions were initiated by the addition of a solution of dimethyl acetylenedicarboxylate (3) (1.1 equiv in 3 ml CH2Cl2) to a solution of benzofuran-2,3-dione derivatives 4 (1 equiv.)and Ph3P in CH2Cl2 (5 ml) at -10 °C.The mixture was stirred for 1 h.Distillation of the solvent in vacuum followed by addition of cold Et2O or EtOH led to a crystalline product 5 in 45-85% yield (Scheme 2).
The products 5a-f were characterized on the basis of their analytical and spectroscopic data.For example, the IR spectrum of 5a displayed characteristic ester C=O absorptions at 1760, 1750 and 1720 cm -1 respectively.In the 1 H NMR spectrum, the two aromatic Me groups appeared as sharp singlets at δ 2.37 and δ 2.65 and the MeO groups resonated at δ 3.89 and δ 4.27.The 13 C NMR spectrum of 5a displayed sixteen distinct signals in agreement with the proposed structure.Partial assignment of these resonances is given in the Experimental Section.The characteristic signal of the spiro carbon atom was discernable at 89.36.Finally, the -spirolactone formation can be rationalized as shown in Scheme 3.

Conclusions
In summary, we have succeeded in synthesizing -spirolactones of potential synthetic interest via a one-pot reaction between dialkyl acetylenedicarboxylates and benzofuran-2,3dione in the presence of triphenylphosphine.High yields of the products, relatively short reaction times, and use of simple starting materials are the main advantages of this method.The reactions were performed under neutral and mild conditions, and the starting materials and reagents can be reacted without any activation or modification.

Experimental Section
Melting points were measured on an Electrothermal 9100 apparatus and are uncorrected.Elemental analyses for C, H, and N were performed using a Heraeus CHN-O-Rapid analyzer.IR spectra were measured on a Perkin-Elmer 783 Infrared spectrophotometer. 1 H and 13 C NMR spectra were measured with a BRUKER DRX-500 AVANCE spectrometer at 500 and 125.77MHz.Mass spectra were recorded on a SHIMADZU GCMS-QP5050 mass spectrometer operating at an ionization potential of 70 eV.Triphenylphosphine, and acetylenic esters 3 were obtained from Fluka (Buchs, Switzerland) and were used without purification.

Table 1 .
The