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

Chapter 8 1708.23.2 Synthesis of 1-aryl-(2-propyn-3-trimethylsilyl)-1-ols 59a-g: general procedure.To a solution of trimethylsilyl acetylene (10 mmol) in dry THF at -78°C n-butyl lithium (10.5 mmol) was added dropwise over 15 min. Thismixture was transferred via a needle to a solution of arylaldehyde in dryTHF at -78°C. The mixture was stirred without further cooling and thetemperature was allowed to raise to 0°C. The reaction was quenched witha saturated solution of NH 4 Cl and diluted with CH 2 Cl 2 and water. Theorganic phase was separated and washed consecutively with saturatedNaCl solution and dried over anhydrous Na 2 SO 4 . The product waspurified by flash chromatography on silica gel.See chapter 5, table 5-1 for products (±)-59a-g and chemical yields.8.23.3 Desilylation of 1-aryl-(2-propyn-3-trimethylsilyl)-1-ols59a-g:8.23.3.1 Desilylation using KF:The (±)-1-aryl-(2-propyn-3-trimethylsilyl)-1-ol (±)-59(10 mmol)was dissolved in 3 ml of DMF, KF (11 mmol) was added, and the mixturewas heated to 60°C for 3 h. It was then cooled to rt and diluted withCH 2 Cl 2 and 1N HCl. The organic phase was separated and washedconsecutively with 1N HCl, water and saturated NaCl solution. It wasfinally dried over anhydrous Na 2 SO 4 . The crude oil was purified by flashchromatography on a silica gel column.See Table 5-2, chapter 5 for products (±)-58a-g and chemicalyields.8.23.3.2 Desilylation using TBAF in dry THF:1-aryl-(2-propyn-3-trimethylsilyl)-1-ol ( 59 ) (10 mmol) wasdissolved in 5 ml of dry THF, the solution was cooled to -20°C and a 1 Nsolution of TBAF in dry THF (11 mmol) was added. The cooling bathwas removed after 1 h and the reaction mixture was stirred at roomtemperature for 4 h. The solvent was evaporated, the crude oil dissolved