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

Chapter 8 16145 min, the mixture was cooled to -15 °C and a solution of 2-bromo-4'-phenylbenzophenone 25c (8.43 g, 25 mmol) in 30 ml of Et 2 O was slowlyadded during 2 h under stirring. After a further 15 min, the reactionmixture was quenched with 1 N NaOH (20 ml). The organic phase wassuccessively washed with 1 N HCl (2 x 100 ml) and 1 N NaOH (2 x 100ml), then with water to neutral pH. Concentration of the dried extractsafforded a crude oil, which was purified by flash chromatography(CHCl 3 /hexane 8:2) to give the title compound.Identical synthetic procedures were used to reduce ketones 25a-dand 26a,c. See chapter 3, table 3.4 for chemical yields and opticalpurities (% e.e.) for 25a-d and chapter 3, table 3.5 for 26a,c.8.6 Dehalogenation of (±)-27c, (+)-27c and (±)-27i:8.6.1 Dehalogenation with Raney Nickel: general procedure.Excess Ra-Ni (50% slurry in water) was added to a solution ofalcohol 27 (2.0 mmol) in 10 ml of MeOH. The mixture was heated toreflux for 30 min. After cooling the reaction mixture was filteredthrough celite and the filtrate was diluted with CHCl 3 , washed with brineand dried. Evaporation of the solvent afforded a residue which waspurified by column chromatography .4-phenyl benzhydrole (±)-27a was recovered in 35% yield and 28n 35%yield.(±)-27i decomposed under identical reaction conditions.8.6.2 Dehalogenation with LiAlH 4 : general procedure.LiAlH 4 (1M THF solution, 2 mmol) was added to a solution of (±)-27c (1 mmol) in dry THF. The reaction mixture was refluxed for 6 h,then cooled to RT and the 1N HCl solution was added to quench thereaction. The product was extracted with CHCl 3 (2x50 ml), the organicphase was dried over anhydrous Na 2 SO 4 . The crude product was purifiedby flash chromatography. 4-Phenyl benzhydrole (±)-27a was recoveredin 89% yield. Identical reactions were carried out with the enantiopure(+)-27c leading to enantiopure (+)-27a in 85 % yield.