General Papers ARKIVOC 2011 (ix) 354-366 Page 354 © ARKAT-USA, Inc. Addition reaction of benzylbenzylidenenamine to lithium enolates of 1,3-dioxolan-4-one: synthesis of 2-phenylisoserines Lizbeth Juárez-Guerra, Susana Rojas-Lima,* and Heraclio López-Ruiz Área Adémica de Química,Universidad Autónoma del Estado de Hidalgo, Carretera Pachuca- Tulancingo Km. 4.5, Ciudad Universitaria, 42184, Mineral de la Reforma Hidalgo, México E-mail: lima@uaeh.edu.mx Abstract The synthesis of two new 2-phenylisoserines, each bearing a quaternary stereocenter is described. These compounds, which are analogs of the amino acid side chain found in taxol and taxotere, were obtained by addition of the lithium enolates of (2S,5S)-2-isopropyl-5-phenyl-1,3- dioxolan-4-one and (2S,5S)-2-tert -butyl-2-methyl-5-phenyl-1,3-dioxolan-4-one to benzylbenzylideneamine in the presence of BF3 . O(Et)2. The diastereomeric mixtures were separated in each case and the absolute configurations thereof were determined by X-ray analysis. Keywords: 2-Phenylisoserines, 1,3-dioxolan-4-one, Mannich reaction, benzylbenzyliden- enamine Introduction The Mannich reaction and transformations involving nucleophilic addition to the C=N of imine derivatives are of significant importance in organic synthesis. 1 Isoserines (α-hydroxy-β-amino acids) are key molecules present in important bioactive substances such as the anticancer agents paclitaxel 1, docetaxel 2 and bestatin 3 (Figure 1). 2 Because of their importance, several efficient methods to synthesize isoserines have been developed. Catalytic asymmetric synthesis and especially asymmetric aminohydroxylation have been applied to the synthesis of the analogs of the docetaxel side chain. 3 Recently, Hu reported an efficient synthesis of α-hydroxy-β-aminoesters containing quaternary stereocenters by trapping imines and diazo compound with oxonium ylide generated in situ from rhodium carbenoids and an alcohol. 4 Most notably, certain catalytic Mannich-type reactions have considerable precedent for the preparation of α -hydroxy-β-amino acids derivatives. 5 Bataglia has developed syntheses of chiral α-substituted isoserines, using cis/trans mixtures of cyclic 1,3- dioxolan-4-one that were not enatiomerically pure. 6 In order to widen the scope of the 1,3-