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

Chapter 5 1302) the hydrolysis of aryl propynol acetates and chloroacetates inpresence of SAMII can be considered a method to obtain Aryl propargylicalcohols of high enantiomeric purity. The use of chloroacetate esters isrecommended due to the higher reaction rates as compared to the acetates.In the case of (±)-61e a higher selectivity (E=50) was also achieved incomparison to the corresponding acetate (±)-60e (E=6);3) it is possible to obtain a SAR (Structure Activity Relationship) forthis class of compounds even if the observed selectivities expressed as Evalues were proven to be strongly dependent on the substitution pattern ofthe benzene moiety, both regarding the type of substituents and theirposition on the aromatic ring. The best position for a substitution of thearomatic ring is the meta position. Higher E values were observed in allcompounds having a meta substituent. No significant differences betweenortho and para position and the E values were detectable. At present thevariety of the substituents is still too small in order to obtain a completeoverview of the stereoelectronic effects. Apparently electrondonors suchas OMe (C.Waldinger's results) decrease dramatically theenantioselectivity, while electronwithdrawing groups increase theenantioselectivity (F and CN). Also a small aliphatic group can increasethe enantioselectivity.5.6 Hydrolysis of enantiopure Acetates (-)-(S)-60a,b,e andchloroacetates (-)-(S)-61b,c,e,h-l resulting from theenzymatic hydrolysis in presence of the lipase SAMII.Acetates (-)-(S)-60a,b,e and chloroacetates (-)-(S)-61b,c,e,h-lresulting from the enzymatic hydrolysis with lipase SAMII had a higherenantiomeric excess as compared to the corresponding alcohols because ofthe extended conversion rates. It was required to use very mild conditionsfor the chemical hydrolysis. A saturated solution of potassium carbonatein methanol at 0°C for 30 min was found to provide the best conditions(Scheme 5.14).