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

Chapter 3 76NCBr 2 ; CH 2 Cl 2NCBrOA2OScheme 3.6: Bromination of 4-Cyano acetophenone .The crude reaction product was used directly without any furtherpurification in the following Rap-Stormer synthesis leading to thecorresponding 4-cyano-2-benzo[b]furanone 26b.In table 3.2 the different ω-bromoacetophenones used as substratesfor the condensation to aryl-benzo[b]furan ketones 26a-e are listed,together with reaction times and obtained chemical yields.Substrate X R Time h ProductYield (%)A1 Br H 12 26a (56)A2 Br 4-CN 16 26b (66)A3 Cl 2,4-Cl 16 26c (88)A4 Br 4-F 14 26d (68)A5 Br 4-Cl 15 26e (72)Table 3.2: Synthesis of aryl-benzo[b]furan ketones 26a-e by the Rap Storner procedure.The chemical yields are moderate. In the case of ω-bromo-4-cyanoacetophenone A2 the chemical yield was calculated based on thecorresponding 4-cyano acetophenone.All compounds 26a-e are precursors for the most active MenariniAromatase inhibitors (see table 1.1, chapter 1 for the activities of thecorresponding compounds). It is interesting to point out that in the literatureno examples for their asymmetric reduction are reported.3.3. Reduction of Prochiral Ketones 25a-f and 26a-e toRacemic Alcohols (±) 27a-m using NaBH 4 .NaBH 4 is one of the most useful reducing agents for ketones. It is easyto handle, generally reacts under mild conditions, does not require