Alternative Strategies for Synthesis of Compounds Based on C-Alkynyl Furan Derivatives

2 Alternative Strategies for Synthesis of Compounds 130 to 133 Based on C-Alkynyl Furan Derivatives 

the four stereoisomeric tetrahydrofuran derivatives (130 to 133) were prepared by following this flexible approach employing (S)- and (/ )-glyceraldehyde derivatives and Sharpless asymmetric epoxidation and double elimination of substituted epichlorohydrin as the key steps. 

Our next concern was to affix the side chain at C2 position via a Lewis acid-mediated nucleophilic addition to A-acyliminium ion diastereoselectively using Ley s phenyl sulfone protocol. However, conversion of the hemiaminal (223) using PhSOjH 

The sulfone derivative (225), when treated with dialkyl zinc reagent prepared in situ from ZnBr2 and 4-tetrahydropyranyloxy-l-butyl magnesium bromide in THF for lOh, reacted smoothly with the substrate to provide homopropargyl pyrrolidine derivative 

It was interesting to note that the HPLC analysis of the final compound showed only one peak with both reverse phase and chiral column, indicating that the minor cis isomer might have been removed from the mixture during purification. There was no NOE enhancement observed during the irradiation of protons at C2 and C5, which suggested that these protons are not in close proximity, thus establishing the trans stereochemistry. 

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