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

Chapter 5 129OClOSAM IIPH=7; R.T.OH O Cl HO HR R RH H H+(±)-61b,c,e,h-l(-)-(S)-61b,c,e,h-l(-)-(R)- 58b,c,e,h-lScheme 5.13: Hydrolysis of Chloroacetates (±)-61b,c,e,h-l by lipase SAM II.The observed reaction rates were much faster as compared to thecorresponding hydrolyses of the acetates. In some cases also the selectivitywas increased. All chloroacetate esters (±)-61 were oils in the reactionmixture. This led to homogeneous reactions and all problems previouslyencountered with the acetate (±)-60e were overcome. Table 5.12 showsthe results.Entry Substrate R C % Time h Product e.e% Yield E1 (±)-61b 4Me 56.4 10 (-)-(S)-61b 97.8 40.69 362 (-)-(R)-58b 75.7 51.03 (±)-61c 4F 53.8 11 (-)-(S)-61c 96.8 44.9 454 (-)-(R)-58c 83.2 53.15 (±)-61e 4CN 53.0 5.5 (-)-(S)-61e 96.6 44.5 506 (-)-(R)-58e 85.5 49.57 (±)-61h 3Me 51.8 4.5 (-)-(S)-61h 99.2 43.5 >1408 (-)-(R)-58h 92.1 46.19 (±)-61i 3F 52.1 2.8 (-)-(S)-61i 99.4 46.2 12710 (-)-(R)-58i 91.5 46.311 (±)-61l 2Me 53.9 22.0 (-)-(S)-61l 94.0 45.1 3912 (-)-(R)-58l 80.4 46.9Table 5.12: Enzymatic resolution of Chloroacetates (±)-61b,c,e,h-l by lipase SAM IIFrom the comparison of the results obtained in this work and takingin account the preliminary results from the master thesis of ClaudiaWaldinger, it is possible to draw some general conclusions:1) the esterification of aryl propynoles by SAMII cannot beconsidered a good process because of the lack of enantioselectivity and theincredibly low rate;