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

Chapter 6 1406.3 Cyclization of racemic and enantiopure 1-Aryl-2-propyn-1-ols 58-a-c,e,h-l to Aryl-benzo[b]furane methanols 27-g,l,hand 63-a-d.The optimal reaction conditions described in paragraph 6.2.3 wereapplied to racemic and enantiopure 1-Aryl-2-propyn-1-ols 58-a-c,e,h-lin order to explore the application of this reaction for the synthesis ofenantiopure Aryl-benzo[b]furane methanols 27-g,l,h and 63-a-d. Thereaction was always applied first to the racemic compound and then to theenantiopure substrate (scheme 6.8).HOH58-a-c,e,h-lRPdCl 2 [P(Ph) 3 ] 2 ; CuITMG, Ar, 40°2-IodophenolOOH27-g,l,h,63-a-dRScheme 6.8: Cyclization of racemic and enantiopure 1-Aryl-2-propyn-1-ols 58-a-c,e,hlto Aryl-benzo[b]furane methanols 27 g,l,h and 63a-d.The results were very satisfactory indeed as reported in table 6.5.Yields were calculated following flash chromatography. This purificationcan be considered a mere filtration through silica since after work up theproducts were always quite pure as judged by NMR and TLC. They were,however, still colored yellow/brown. The enantiomeric excess wasdetermined by chiral HPLC of the crude materials (after the reactionwork up) prior to purification. It is interesting to note that the e.e. did notchange from the chiral starting material to the product before and afterpurification.This method gave very reproducible results both in terms ofchemical yields and enantiomeric excess. From the results shown in table6.5 it is clear that different substituents on the aromatic ring did not leadto any modification of the results.They were also not influenced by the position of the substituent onthe aromatic ring (see entries 3,4,8,9,12,13; table 5.6) nor bystereoelectronic effects (see entries 1,2,3,4,5,6; table 5.6).