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

Chapter 6 1386.2.4. Optimization of catalyst (Pd) amount and CuI.The last attempt of optimization was aimed at the reduction of theamount of Pd catalyst and copper iodide. Five experiments were carriedout to find the best molar ratio (Table 6.4; scheme 6.7).HOH(±)-58aPdCl 2 [P(Ph) 3 ] 2 /CuITMG, Ar, 40°2-IodophenolOOH(±)-27gScheme 6.7: Optimization of Pd catalyst/ CuI ratio.In the first experiment the ratio reported in the original publication wasused where Pd catalyst and CuI were present in 0.035 and 0.13 Mol% inrespect to the 2-iodophenole. The chemical yield was very high (table 6.4;entry 1). In the second experiment the amount of CuI was reduced inorder to have an equimolar ratio betweeen Pd catalyst and CuI (entry 2,Table 6.7).Entry Substrate Molar ratio Pd/CuI Time h Product Yield1 (±)-58a 0.035:0.13 4< (±)-27g 90.02 (±)-58a 0.035:0.035 4< (±)-27g 90.03 (±)-58a 0.025:0.025 4< (±)-27g 90.04 (±)-58a 0.010:0.025 40 (±)-27g 40.3Table 6.4: Optimization of catalyst (Pd) amount and CuI.Again the chemical yield was identical to the previous experimentand proved that an excess of CuI is unnecessary.In the third experimentthe amounts of Pd and CuI were reduced to 2.5 Mol% (entry 3, table 6.4).Again an identical result was obtained. In the last experiment only 1% ofPd catalyst and CuI were used (entry 4, Table 6.4), leading to (±)-27g in40% yield. The observation that both 2-iodophenol and the startingmaterial (±)-58a were completely consumed during the reaction led tothe discovery of a very polar side product which, after isolation andcharacterization, was identified to be the uncyclized product (±)-62.