Reactions of cyclohexyl isocyanide , dialkyl acetylenedicarboxylates and 1-aryl-2-ene-3-acetyl-1 , 4-diketones : one-pot synthesis of highly functionalized 5-cyclohexylimino-2 , 5-dihydrofurans

Dihydrofurans are important intermediates in organic synthesis, and are also important starting materials used in syntheses of a number of natural products. A facile synthesis of highly functionalized 5cyclohexylimino-2,5-dihydrofuran derivatives by the multi-component reaction of cyclohexyl isocyanide, dialkyl acetylenedicarboxylates and 1-aryl-2-ene-3-acetyl-1,4-diketones is described.


Introduction
The Michael addition of isocyanides to activated carbon-carbon multiple bonds produces reactive zwitterionic intermediates which may be trapped by carbon or hydrogen proton electrophiles to afford a wide range of carbocyclic or heterocyclic organic compounds.It has been reported that isocyanides attack dialkyl acetylenedicarboxylates (DAADs), yielding zwitterionic species which could be trapped by the carbonyl group of aldehydes, 1 ketones, 2 esters, 3 isocyanates, 4 acyl chlorides 5 , and even carbon dioxide 6 , to afford five-to seven-membered oxygen and nitrogen heterocyclic compounds.
Multi-component reactions of arylglyoxals have recently attracted much attention for the synthesis of a wide range of important heterocyclic compounds.The application of arylglyoxals for the preparation of threeto six-membered heterocyclic compounds has been recently reviewed. 7ihydrofurans are important intermediates in organic synthesis and have been attracting much attention in synthetic studies 8,9 .1][12][13][14][15][16][17] 2,5-Disubstituted dihydrofuran-3,4-dicarboxylates are important starting materials which have been used for the synthesis of some natural products. 18Thus, developing new, simple and efficient syntheses of dihydrofuran derivatives have been an area of interest.
In recent years, we have been focusing our attention on the applicability of multi-component reactions of isocyanides 19,20 and arylglyoxals 21,22 for the synthesis of heterocyclic compounds.In continuation of our studies in this area, we wish to report, herein, the reaction of 1-aryl-2-ene-3-acetyl-1,4-diketone derivatives, prepared by Knoevenagel condensation of arylglyoxals with acetylacetone, 22 with isocyanides and DAADs to produce 5-imino-2,5-dihydrofuran derivatives in good yields.
To investigate the scope of the reaction, different DAADs were treated with cyclohexyl isocyanide and different 1-aryl-2-ene-3-acetyl-1,4-diketones.The corresponding 5-cyclohexylimino-2,5-dihydrofuran derivatives 4a-i were obtained in good yields (Scheme 1).The structures of compounds 4a-i were deduced from their elemental analyses and their infrared (IR), 1 H NMR, and 13 C NMR spectral data.The 400-MHz 1 H NMR spectrum of 4a exhibited five sharp signals at δ 2.34, 2.39, 2.42, 3.80 and 3.96 ppm for the three methyl and two methoxy groups.The cyclohexyl protons resonated as multiplets at 1.22-1.85(5 CH 2 ) and at 3.51 (CH) ppm.The aromatic protons resonated as a multiplet at 7.25 ppm and the olefinic CH was observed at 7.44 ppm as a singlet.The 13 C NMR spectrum of compound 4a showed twenty-five distinct resonances in agreement with the proposed structure.The structural assignment for compound 4a, made on the basis of the NMR spectra, were supported by its IR spectrum as the ester carbonyl groups exhibited strong absorption bands at about 1755 and 1724cm -1 , respectively.The ketone carbonyls were observed as strong absorptions at 1684 and 1669 cm -1 , respectively.
In conclusion, we have developed a simple and efficient method for preparation of functionalized 5cyclohexylimino-2,5-dihydrofuran derivatives by a three-component reaction of cyclohexyl isocyanide, dialkyl acetylenedicarboxylates and 1-aryl-2-ene-3-acetyl-1,4-diketone derivatives.This method has the advantages that the reactions can be performed under neutral conditions with readily available starting materials which require no modification or preparation.

Experimental Section
General.All of the utilized arylglyoxals were prepared by the SeO 2 -oxidation of the related aryl methyl ketones on the basis of the reported procedure and used as their monohydrates. 24Elemental analyses were performed using a Heraeus CHN-O-Rapidanalyzer. IR spectra were recorded on a Shimadzu IR-470 spectrometer. 1 H and 13 C NMR spectra were recorded on a Bruker DRX-400 Avance spectrometer at 400 and 100 MH Z , respectively.
The chemicals used in this work were purchased from Merck and used without further purification.