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

Chapter 5 1145. Synthesis of Aryl propargylic alcohols of highenantiomeric purity via Lipase catalysedresolution.The aim of this part of the thesis was the synthesis of aryl propargylicalcohols in enantiopure form, useful building blocks for the synthesis of aryl2benzo[b]furane methanoles 27 and the Menarini imidazole derivative 18 inenantiopure form.5.1 Synthesis of racemic 1-Aryl 2-propyne-2-ols (±)-58.Several methods are described in the literature 1a,b,c for the synthesisof racemic ethynyl carbinoles. The most useful procedure is the additionof various nucleophilic reagents to aldehydes or ketones, monolithiumacetylide being one example. Several methods for the preparation of thisreagent 2a,b are reported in literature. One of the procedures involves theaddition of n-butyl lithium to acetylen in dry THF at -78°C followed bythe addition of aldehydes or ketones 3a,b . The reported yields of ethynylcarbinoles are high, but the experimental procedure is very complex.Furthermore, the use of acetylene bottles in chemistry departments isregulated by very restricted laws. Lithium acetylide is commerciallyavailable as 0,1 N THF solution, and this was used as nucleophile for theaddition to the benzaldehyde. In the second procedure, ethylenediaminewas used to stabilize the acetylide 3b . Both experiments gave very poorresults, only 45% and 42% yield of 1-Phenyl-2-propyn-1-ol (±)-58a,respectively were obtained (Scheme 5.1).RH1)H SiMe 3nBuLidry THF -78 0 CRSiMe 3O2) dry THF -78/0 0 COH(±)-59 a-gScheme 5.1:Synthesis of 1 Phenyl-2-propyn-1-ol (±)-58a.The biggest problem encountered with lithium acetylide is itsdisproportionation to form dilithium acetylide and acetylene 3b . In order