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

Chapter 3 75literature as the best substrate for this kind of asymmetric reduction.2-Bromo-4'-phenyl benzophenone 25c can be considered asprecursor of bifonazole. The ortho substituent is required for goodenantioselectivity during the Brown asymmetric reduction, while thepara phenyl group is required for the bifonazole structure. The paraphenyl group on the aromatic moiety of the molecule does notinterfere with the process of chiral recognition by the chiral LAHcomplex.The Friedel-Craft's acylation of the biphenyl moiety with all aroylchlorides Aa-f proceded with high regioselectivity, biphenyl was onlymonoacylated in the para position with respect to the second aromatic ring.Reactions were followed by both GC-MS and 1 H-NMR after work upwithout any purification.The chemical yields were always very high.3.2. Synthesis of Aryl-2-Benzo-[b]-Furanones 26 a-e: ProchiralKetones for the Menarini Anticancer Drugs 18 via theRap Stormer procedure.The synthesis of Aryl-2-benzo-[b]-furan ketones 26a-e was achievedvia the Rap Stormer procedure. For this the ω-bromo-acetophenones A 1-5 were condensed with salicyl aldehyde B under basic conditions (scheme3.5) leading to the ketones 26a-e.XOHEtO - Na +RO+HOEtOH 60°CROOA 1-5X = Cl, Br.B26 a-eScheme 3.5: Synthesis of Aryl-Benzo[b]furan Ketones 26 a-e.The required ω-Bromo-acetophenones A1,3-5 were commerciallyavailable, while A2 was prepared from the corresponding 4-cyanoacetophenone by bromination with molecular bromine in chloroformat room temperature in high (88%) yield (Scheme3.6).