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

Chapter 8 178addition of N-Mesyl-2-iodoaniline 46 (297.11 mg, 1 mmol), bistriphenylphosphinepalladium (II) dichloride ( 17.5 mg, 0.025 mmol),CuI (4.5mg, 0.025 mmol) and 1-phenyl-2-propyn-1-ol 58a ( 123.9 µl,1mmol). The mixture was stirred under Argon at 40°C for 4 whereby thecolor changed from pale yellow to red/brown. After cooling, the reactionmixture was diluted with 1N HCl solution and ethyl acetate. The organiclayer was separated and washed consecutively with water and saturatedNaCl solution and was finally dried over anhydrous Na 2 SO 4 . Afterevaporation of the solvent the crude resulting oil was purified by flashchromatography on silica gel to afford (±)-64a in 87% chemical yield.The same experimental procedure was applied to all of the racemicand enantiopure aryl propynols 58a-c,e,h-l. See chapter 6, table 6.7 forreaction times, chemical yields and enantiomeric excesses.8.35 Synthesis of (2'-Hydroxyphenyl)-2-propyn-1-phenyl-1-ol(±)-62.(±)-62 can be obtained as side product in the synthesis of 1-phenyl-2-benzo[b]furane carbinol (±)-27g using 1% of palladium catalyst andCuI (see Chapter 6.2.4.) or by using one equivalent of base (TMG,Chapter 6.3.1) The second procedure is described below.Argon was bubbled thruogh a solution of tetramethylguanidine(TMG, 125 µl, 1 mmol) in 2.5 ml of DMF for 15 min at 40°C before theaddition of 2-iodophenol (220.01 mg, 1 mmol), bis-triphenylphosphinepalladium (II) dichloride ( 7.5 mg, 0.010 mmol), CuI (1.8 mg, 0.010mmol) and 1-Phenyl-2-propyn-1-ol (±)-58a ( 123.9 µl, 1mmol). Themixture was stirred under argon at 40°C for 4 h, whereby the colorchanged from pale yellow to red/brown. After cooling, the reactionmixture was diluted with 1N HCl solution and ethyl acetate. The organiclayer was separated and washed with water, saturated NaCl solution andwas finally dried over anhydrous Na 2 SO 4 . After evaporation of thesolvent the resulting crude oil was purified by flash chromatography onsilica gel to afford (±)-62 in 90% chemical yield.8.36 Synthesis of racemic 1-Phenyl-3-(2'acetoxyphenyl)-2-propyn-1-ole (±)-71.