Regio- and stereoselective microwave-assisted synthesis of 5-alkyl-4-alkenyl-4-phenyl-1,3-oxazolidin-2-ones Marta Amador a , Xavier Ariza a, * , Jérémie Boyer a , Lucia D’Andrea b , Jordi Garcia a, * , Jaume Granell b a Departament de Química Orgànica and IBUB, Universitat de Barcelona, C/Martí i Franquès 1-11, E-08028-Barcelona, Spain b Departament de Química Inorgànica and IBUB, Universitat de Barcelona, C/Martí i Franquès 1-11, E-08028-Barcelona, Spain article info Article history: Received 17 November 2009 Revised 3 December 2009 Accepted 8 December 2009 Available online 16 December 2009 Keywords: Palladium catalysts Nickel catalysts Microwave-assisted synthesis 1,4-Diols Quaternary a-amino acids abstract Chiral symmetrical alk-2-yne-1,4-diols have been stereoselectively transformed into 5-alkyl-4-alkenyl-4- phenyl-1,3-oxazolidin-2-ones, which are precursors of quaternary a-amino b-hydroxy acids. The key step was the cyclization of the bis(tosylcarbamates) of 2-phenylalk-2-yne-1,4-diols, easily obtained from the starting chiral diols. These cyclizations were accomplished with complete regioselectivity and up to 92:8 dr in the presence of catalytic amounts of Ni(0) or Pd (II) derivatives under microwave heating. Ó 2009 Elsevier Ltd. All rights reserved. Enantioenriched 1,4-diols have been shown to be versatile syn- thons for asymmetric synthesis. 1 In the course of a project aimed to develop synthetic applications of unsaturated 1,4-diols, 2 we have recently reported the preparation of both erythro and threo b-hy- droxy a-amino acids from a common precursor, namely a C 2 -sym- metrical alk-2-yne-1,4-diol (1)(Scheme 1). 3 The key step of our approach was a stereoselective Pd(0)-catalyzed intramolecular N- alkylation of the allylic (Z)- or (E)-1,4-dicarbamates (2) derived from 1. 4 It should be noted that due to the C 2 -symmetrical proper- ties of the starting materials, only one regioisomer was possible in such processes. Herein, we extend the scope of our work to allylic 1,4-dicarba- mates 3, in which symmetry is broken by an additional substituent R 0 on the double bond. Cyclization on 3 is a challenging issue since two regioisomers, 4 and 5 are possible (Scheme 2). We were inter- ested in the preferential formation of carbamates 4, potential pre- cursors of quaternary amino acids after the oxidative cleavage of the double bond. In particular, we envisaged that when R 0 = Ph in 3, the ionization of the carbamate group on C(4) leading to 4, will be favored for steric and electronic reasons. Thus, the Ph group could better extend the conjugation of the transient p-allylic cat- ions in a Pd(0)-catalyzed process. Thus, we embarked on a study aimed to obtain compounds 3 (with R 0 = Ph) and their further transformation into the quaternary carbamates 4. We wish to report herein our findings in this connection. As expected starting chiral diols 1 were readily desymmetrized by reaction with phenylboronic acid in the presence of [Pd(PPh 3 ) 4 ]. 5 As observed in Scheme 3, diols 6a–d were isolated in 50–78% yield with complete Z selectivity using 2 mol % of Pd cat- alyst and 10 mol % of AcOH in dioxane. 6 Diols 6 were quantitatively transformed into dicarbamates 3 by treatment with tosyl isocya- nate (2 equiv) in CH 2 Cl 2 . We chose 3b as a representative model to test the cyclization step. We first applied the experimental conditions used for the Pd(0)-catalyzed intramolecular N-alkylation of 2. 3a Unfortunately, the expected quaternary compound 4b was not observed or ap- peared just as a minor component in a mixture (Table 1, entries 1 and 2). A series of experiments were then undertaken in which 0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2009.12.036 * Corresponding authors. Tel.: +34 934034819; fax: +34 933397878 (J.G.). E-mail addresses: xariza@ub.edu (X. Ariza), jordigarciagomez@ub.edu (J. Garcia). R R OH OH R R O O NHTs TsHN O O O N R O Ts R R CO 2 – OH NH 3 + R CO 2 – OH NH 3 + Pd(0) cat. erythro threo 1 2 or Scheme 1. Reported synthesis of erythro and threo b-hydroxy a-amino acids. Tetrahedron Letters 51 (2010) 935–938 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet