DAST mediated preparation of b-fluoro-a-aminophosphonates Marcin Kaz ´ mierczak, Henryk Koroniak * Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, 60-780 Poznan ´, Poland 1. Introduction Organophosphorus compounds are important substrates in biochemical processes. They are potent bioactive molecules used as agrochemicals and pharmaceuticals, as well as effective enzyme inhibitors [1]. It is also known, that the introduction of fluorine atom(s) into organic molecules may change their chemical, physical and biological properties [2]. These fundamental observa- tions are the conceptual base for studies on new organophospho- rus–fluorine containing compounds. For example, it has been shown that fluorinated aminophosphonates are useful inhibitors of many enzymes [3]. Cytotoxic and antibacterial activities has been reported for some of the fluorine-containing aminopho- sphonates [4]. To the best of our knowledge, there are only a few examples of synthesis of b-fluorinated a-aminoalkylphospho- nates, which have been found to be an inhibitor of alanine racemase (Scheme 1) [5]. Nucleophilic fluorination is one of the common methods of introduction of a fluorine atom into organic compounds [6]. It should be noted that fluorine-containing reagents are usually poor nucleophiles. Fluoride itself is the smallest anion which can form strong hydrogen bonds, however, its solvation can dramatically decrease its nucleophilicity by the formation of stable solvation shells [2]. One of the most common procedures to introduce fluorine atom to phosphonate system is the replacement of hydroxyl group with fluorine. The common and quite useful reagent (stable and commercially available) which can be used is DAST (diethylaminosulfur trifluoride) [7]. However, mechanism of fluorination with DAST in case of a-hydroxyphosphonates depends of the phosphonate system [8]. In this paper we would like to report, neighbouring group participation during DAST-mediated fluorination of series of simple b-amino-a-hydroxyphosphonates. We believe, this is the first example of direct access to various b-fluoro-a-aminopho- sphonates. 2. Results and discussion Our synthetic strategy was to synthesize series of N-protected a-hydroxyphosphonates (Scheme 2) and next, modify the mole- cule via introduction a fluorine atom into this system. As starting material a series of simple alkyl and aryl a-amino acids had been chosen. At first a-amino acids 1a–e (1a- Glycine, 1b- L-Alanine, 1c- L-Leucine, 1d- L-Phenylalanine, 1e- D-Phenylglycine) were trans- formed into N,N-dibenzylamino alcohols 2a–e in two step procedure with good yields. First benzylation with BnBr in presence of K 2 CO 3 in water at 80 8C and next reduction of obtained Journal of Fluorine Chemistry 139 (2012) 23–27 A R T I C L E I N F O Article history: Received 10 February 2012 Received in revised form 18 March 2012 Accepted 21 March 2012 Available online 6 April 2012 Keywords: Fluorination DAST Phosphonates Aminophophonates Aziridinium ion A B S T R A C T Herein, we report a new and convenient method for the synthesis of b-fluoro-a-aminophosphonates starting from naturally occurring L-amino acids. A key step in the synthetic protocol involves nucleophilic fluorination of N,N-dibenzylated-b-amino alcohols with diethylaminosulfur trifluoride (DAST). ß 2012 Elsevier B.V. All rights reserved. Scheme 1. * Corresponding author. Tel.: +48 618291303; fax: +48 618291505. E-mail address: koroniak@amu.edu.pl (H. Koroniak). Contents lists available at SciVerse ScienceDirect Journal of Fluorine Chemistry jo ur n al h o mep ag e: www .elsevier .c om /loc ate/f luo r 0022-1139/$ – see front matter ß 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jfluchem.2012.03.016