text: K. C. Nicolaous group successfully synthesized endiandric acid, 1, in 1982 as a test of Blacks biosynthetic conjecture, using a biomimetic strategy involving series of stereocontrolled electrocyclic reactions. Specifically, they observed that the natural products endiandric acids A and C could have arisen from a common precursor, via slightly different 6π [4s+2s] cycloaddition (Diels-Alder) reactions. This key precursor was in turn accessible biosynthetically via two further thermally allowed sequential 6π electron and 8π electron electrocyclizations.
  The Nicolaou group therefore sought to synthesize endiandric acid C from an acyclic symmetric diacetylenic diol precursor, 14 (as shown); they began with "mild hydrogenation" in the presence of Lindlar catalyst and quinoline, anticipating tetraene diol 15, cyclooctatriene 16, or the fully cyclized bicyclo[4.2.0]octadiene (bicyclic diol) 17. Remarkably, following this 3-6 hour, 25 °C process, a 45-55% yield of bicyclic diol 17 could be isolated. Hence, it was not necessary to do anything specific to promote the required sequence of 8π conrotatory and 6π disrotatory cyclizations (further highlighted in supplementary image); they occurred spontaneously on generation of tetraene-diol 15.  Protection of a single alcohol moiety (as TBDPS) was accomplished using the silyl chloride via the corresponding tricyclic iodoether intermediate (not shown), with the internally masked remaining hydroxyl group being released on treatment with zinc dust in acetic acid (giving 18 in 70-80% yield). Bromination of the alcohol under Appel conditions followed by its displacement on treatment with sodium cyanide in HMPA gave nitrile 20, the key intermediate in all of this groups endiandric acid syntheses.'
  The title compound was then pursued via DIBAL reduction of the nitrile at low temperature, followed by mild acidic hydrolysis to release aldehyde 21. A series of 7 further steps—condensation to form trans-butenoate 22, thermal intramolecular Diels-Alder reaction to create the tetracyclic endiantric core structure 23, desilylation to unmask alcohol  24, bromination and nitrile formation (as described above) to give  25 and  26, respectively, then hydrolysis of the methyl ester and repeat of the earlier DIBAL/acid hydrolysis sequence—generated the endiantric core structure with pendant aldehyde, 28, that was poised for the final step.  Its treatment with diethyl cinnamylphosphonate and LDA at low temperature in THF (generating en route the anionic olefination reagent) formed the desired diene in good yield in a "geometrically controlled manner", thus providing the desired endiandric acid C product.