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

Chapter 5 119Entry R T °C Product Yield1 4H 0 (±)-58a 992 4Me -15 (±)-58b 983 4F 0 (±)-58c 894 4CN -78 (±)-58e 905 3Me 0 (±)-58h 916 3F 0 (±)-58i 787 2Me 0 (±)-58l 988 2,4Cl 0 (±)-58m 98Table 5.4: Reaction conditions and chemical yields for the synthisis of aryl-propynols(±)-58a-c,e,h-m.The chemical yields were very high, the reaction conditions mild andall products could be purified by easy filtration over silica gel. In orderto obtain a colorless liquid it was necessary to distill the crude productsunder high vacuum. The cyano group present in 4-cyano benzaldehydeproved to be unreactive with the Grignard reagent also in presence of aslight excess.5.3 Enzymatic resolution of 2-substituted-2-propynyl-1-oles(±)-58.In the literature several methods for the enzymatic resolution ofacetylenic alcohols by hydrolysis or esterification are reported. O'Hagan 8has reported a very good study of the resolution of tertiary acetyleneacetate esters in presence of a lipase from Candida cylindracea. However,the enantiomeric excesses usually are very low. Much more efficient is theesterification of secondary acetylenic alcohols in presence of Pseudomonas(A.K.) in hexane with vinyl acetate 9 . In these cases e.e.'s higher than 95%were reported both for the alcohol and the acetate. E values are higherthan 200. Unfortunately, the paper describes only one kinetic resolutionof a secondary propynyl alcohol with an internal triple bond. Only oneexample describes a terminal triple bond and this was the worst substrate,leading to only very low enantiomeric excess. In the master thesis ofClaudia Waldinger 6 preliminary results were reported concerning theenzymatic resolution of four different terminal aryl propynoles byhydrolysis or esterification in presence of a lipase from Pseudomonas