SYNTHESIS OF STABILIZED PHOSPHORUS YLIDES FROM ELECTRON-POOR ALCOHOLS AND THEIR APPLICATIONS IN THE PREPARATION OF 2 , 5-DIHYDROFURAN DERIVATIVES

Protonation of the highly reactive 1:1 intermediates, produced in the reaction between triphenylphosphine and dialkyl acetylenedicarboxylates, by alcohols (2-methanol thiophen, 3-methanol thiophen, 1,1,1,3,3,3-hexafluoro-2-propanol and [4-(trifluoromethyl)-phenyl]methanol) leads to vinyltriphenylphosphonium salts, which undergo Michael addition reaction with conjugate base to produce the corresponding stabilized phosphorus ylides. Wittig reaction of the stabilized phosphorus ylides with ninhydrin leads to the corresponding densely functionalized 2H-indeno[2,1-b]furans in fairly good yields.

Compounds with [2,1-b]furan skeleton have attracted interest in bio-organic, natural products and medicinal chemistry.They show pharmaceutical and biological activities including antimicrobial and anti-fungal effects [17][18][19][20].Since years acetylenic esters have attracted the attention of organic chemists, mostly as Michael acceptors [2].In recent years, there has been increasing interest on the applications of acetylenic esters in multi-component syntheses [2], specially for preparing stabilized phosphorus ylides [2].Due to atom economy, convergent character and simplicity of one-pot procedures, multi-component condensation reactions (MCRs) have great potentials in synthesis.The development of novel MCRs is also receiving growing interest from industrial chemistry research groups and represents a challenge for organic chemists [21,22].Few methods have been reported in the literature for the synthesis of indeno[2,1-b]furans [18,19].These protocols are multi-step in nature.

RESULTS AND DISCUSSION
Reactions are known in which an α,β-unsaturated carbonyl compound is produced from a phosphorane and a carbonyl compound such as an aldehyde or ketone [7,16].Thus, compounds 10a-h may be regarded as the product of an intramolecular Wittig reaction.Such additionolefination products may result from an initial addition of triphenylphosphine 1 to the acetylenic ester 2 and concomitant protonation of the 1:1 adduct, followed by attack of the anion 4 of electron-poor alcohol 3 on the vinylphosphonium ion to form the stabilized phosphorane 5.It seems that the compounds 4 and 5 are in equilibrium in CH 2 Cl 2 at room temperature.Addition of 4 to the highly electron-deficient carbonyl group of indane-1,2,3-trione (7) leads to the formation of the vinyltriphenylphosphonium salt 8 that converts to phosphorus ylide 9.
Intramolecular Wittig reaction of the phosphorus ylide 9 will then lead to the formation of corresponding 2H-indeno[2,1-b]furan derivatives 10a-h and triphenylphosphine oxide (Scheme 1 and Table 1).TLC results indicated that the reactions are completed after 24 h in CH 2 Cl 2 at room temperature.The reactions proceed smoothly and cleanly under mild conditions and no side reactions were observed.The mechanism of the reaction has not been established experimentally.However, the reaction sequences proposed in Scheme 1 are plausible.

CONCLUSIONS
In conclusion, the reported method offers a mild, simple, and efficient route for the diastereoselective synthesis of dihydrofuran derivatives 10a-h.The ease of work-up, good yields and fairly mild reaction conditions make it a useful addition to modern synthetic methodologies.Other aspects of this process are under investigation.

EXPERIMENTAL
Melting points were measured on an Electrothermal 9100 apparatus and are uncorrected.IR spectra were recorded on a Shimadzu IR-460 spectrometer. 1 H and 13 C NMR spectra were measured with a Bruker Spectrospin spectrometer at 250 and 62.5 MHz, respectively.
a Isolated yields.