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

Chapter 4 8933a-m were hydrolysed to the dicarboxylic acid derivatives 34a-m withNaOH and finally 34a-m were converted via a decarboxylation step into thefinal imidazole products 35a-m (Scheme 4.2).OHCNNNH32R 1 R 2NCNDEAD PPh 3CNNR 1 R 2CN31a-i,27a-c,g,m33 a-mHydrolysisCO 2 HNNDecarboxylationNNCO 2 HR 1 R 235a-mR 1 R 234a-mScheme 4.2: Synthetic pathway, Mitsunobu reaction-Hydrolysis-Decarboxylation.The racemic and enantiopure alcohols 31a-f and 27a-c,g,m were usedas alkylating agents in order to establish the stereochemical outcome of theMitsunobu reaction with 4,5 dicyanoimidazole 32. Alcohols 31 a-f arecommercially available both in racemic and enantiopure form. Alcohols27a-c,g,m (entries 11-19 tab 4.1) were synthesized as reported in chapter 3.Results are summarized in Tab. 4.1.31a-f and 27a-c,e,g,m were chosen in order to obtain a completepicture of the potential and limits of this methodology; the substrates areprimary, secondary, aliphatic, homobenzylic, benzylic, and benzyhydrilicalcohols. Tertiary alcohols such as t-butanol are unreactive. The resultswere very interesting indeed because it was now possible to understand thereal limits of the methodology. Special attention was dedicated to thestereochemical control rather than the chemical yield.