Stepwise, Stereocontrolled Total Synthesis Of Endiandric Acids A-D and E-G

1 Stepwise, Stereocontrolled Total Synthesis of Endiandric Acids A-D (and E-G) 

The key intermediate 25 was prepared efficiently from aldehyde 23, obtained by reduction of nitrile 22 with Dibal-H. Treatment of 23 with the lithium salt of frans-diethyl cinnamylphosphonate furnishes compound 24 in 75 % yield and with a 20 1 ratio of E Z olefin stereoisomers. The stage is now set for the final and crucial operations to complete the molecular skeletons of endiandric acids A and B. 

Gratifyingly, when compound 24 is refluxed in a solution of toluene at 110°C, it undergoes quantitative [4+2] cycloaddition to polycyclic system 25. The indicated stereochemistry of 25 was anticipated on the basis of the trans,trans geometry of the phenyl-diene system in precursor 24 and the presumed preference for an exo transition state geometry. These assumptions were vindicated by the eventual conversion of 25 to endiandric acids A (1) and B (2). 

With the demonstration of the pathways described above it became abundantly clear that the formation of endiandric acids in nature from polyunsaturated achiral precursors is quite feasible without the participation of enzymes, as Black had so insightfully suggested in 1980. 

The thermally induced reactions of endiandric acids F and G methyl esters (59 and 60) were followed in a similar fashion 

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