Advances in the stereoselective synthesis of antifungal agents and ...

Chapter 6 150between aryliodide and copper acetylide and not in the final cyclizationstep. A third attempt was made by using the normal cyclization conditionsfor the synthesis of benzofurans (±)-27g using palladium catalysis. (±)-62 as expected cyclized in less than three hours to the benzofuranes (±)-27g in 89% yield (Scheme 6.24)OHOHPdCl 2 [P(Ph) 3 ] 2 , TMG(±)-62 CuI, 40°C,DMF(±)-27gOOHScheme 6.24: Cyclization of (±)-62 under the optimized conditions for the synthesis ofaryl benzofuran carbinols.A final attempt was made by adding CuI and TMG to a solution of(±)-62 in DMF at 40°C under argon. Here in less than one hour (±)-62was converted completely to the benzofurane (±)-27g. The result provedagain that cyclization takes place only in presence of CuI in basic media.OHOHCuI, TMG(±)-62 40°C,DMF(±)-27gOOHScheme 6.25: Cyclization of (±)-62 to aryl benzofuran carbinol (±)-27g by copperiodide.The process is clearly copper mediated as hypothesized in Castro'spublications (Scheme 6.25).The four different experiments decribed above clearly indicate thatthe palladium catalyst is involved only in the crosscoupling between aryliodide and the acetylenic compound to form compounds such as (±)-62but not in the final cyclization step to benzo[b]furane. Theheteroannulation is not working by simple organic base catalysis asproven in the first experiment where tetramethyl guanidine was used asbase to cyclize (±)-62. In reality it is mediated by the copper iodide in