Long range phosphorus–phosphorus coupling constants in bis(phosphorylhydroxymethyl)benzene derivatives Marek Doskocz, Barbara Malinowska * , Piotr Młynarz, Barbara Lejczak, Paweł Kafarski Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wybrze _ ze Wyspian ´skiego 27, 50-370 Wrocław, Poland article info Article history: Received 23 March 2010 Revised 14 April 2010 Accepted 23 April 2010 Available online 28 April 2010 abstract Long range spin–spin couplings found between two phosphorus atoms are quite rare phenomena. A new example of such a coupling through seven bonds is described for 1-[(diethoxyphosphoryl)butyryloxym- ethyl]-4-[(diethoxyphosphoryl)hydroxymethyl]benzene and 1,4-bis[phosphorylhydroxymethyl]benzene and through six bonds for tetraethyl phenylene-1,3-(bishydroxymethylphosphonate). Coupling constants in this system are also well predicted by theoretical studies. Published by Elsevier Ltd. 1. Introduction Nuclear Magnetic Resonance (NMR) is a useful technique for the characterization of the three dimensional structure of chemical and biological systems ranging from small molecules 1,2 to complex biological polymers such as nucleic acids and proteins. Coupling constants are one of the most important parameters here since they supply information on the geometry and dynamics of individ- ual moieties in a molecule, leading to the determination of its con- formation. 3 In phosphorus organic chemistry, the NMR technique is based on the magnetic properties of phosphorus nuclei. 1,3 Coupling constants across more than four bonds have been named ‘Long Range Couplings’ (LR). In phosphorus compounds the LR between 31 P and 1 H( n J PH ) and 31 P and 13 C atoms ( n J PC ) have been studied by many researchers. 4 Khaleeluddin, Scott, Gordon, and Griffin reported such couplings via five to seven bonds. 5–7 The origin of LR lies in that fragments of the molecule are rich in p-elec- trons (aromatic rings, double or triple bonds). Another type of coupling interaction between phosphorus atoms involves spin– spin interactions across hydrogen bonds ( nh J XY , where n is the number of bonds between coupled atoms (X,Y) and couplings via hydrogen bond denoted as h), for example, in phosphazene sponges ( 4h J PP P@NH + ÁÁÁN@P), 8,9 N–HÁÁÁO@P, and O–HÁÁÁO@P( 3h J PN , 2h J PH ) in Desulfovibrio vulgaris flavodoxin, 10–14 C–HÁÁÁO@P( 3h J PC , 2h J PH ) in model phosphate-guanine, and bishydroxybisphosphonates. 15,16 LR couplings may also occur via ‘through-space’ interactions ( ts J XY ), for example, in tetraphosphine ferrocenyl derivatives, as a result of overlapping of lone pairs of orbitals in two close elements. 17 Repre- sentative examples of structures exemplifying each of these types of couplings are collected in Table 1. Long range couplings between two phosphorus atoms are quite rarely observed (Table 1). In many cases the mechanism of spin–spin transfer interactions between atoms is a cumulative effect of several factors, which are impossible to define precisely. In this Letter, we report a new class of phosphonates represented by 1-[(diethoxyphosphoryl)butyryloxymethyl-oxym- ethyl]-4-[(diethoxyphosphoryl)hydroxymethyl]benzene ( A), 1,4-bis[phosphorylhydroxymethyl]benzene (B), and 1,3-bis[(dieth- oxyphosphoryl)hydroxymethyl]benzene (C) (Scheme 1), 30 in which such long range coupling constants have been detected. Compound A was obtained as a single enantiomer by biocatal- ysis (RR), whereas compound B was a single diastereomer (RR,SS), while compound C was a mixture (RR/SS and meso). Consequently in the 31 P NMR spectra of B the phosphorus signal is a singlet and in C, it is a doublet. Here we present an experimental and theoret- ical examination of long range coupling phenomenon in these compounds. 2. Registration of J PP couplings Interpretation of the 31 P{ 1 H} NMR spectra of the studied com- pounds indicated the presence of intramolecular couplings. Deter- mination of coupling constants may not always be straightforward, especially taking into consideration the fact that the studied com- pounds may appear as diastereoisomers and signals may overlap. Therefore, the correlation of several NMR techniques was required. Experimental investigations to determine n J PP couplings were carried out according to standard procedures applying 1D and 2D NMR techniques. There are a few known NMR methods delineating P–P interactions. The simplest method of determining n J PP couplings is interpre- tation of the multiplet structure of 31 P{ 1 H} NMR spectra of com- pounds with different chemical shifts for each phosphorus atom belonging to the same molecule, as is the case in compound A. 0040-4039/$ - see front matter Published by Elsevier Ltd. doi:10.1016/j.tetlet.2010.04.107 * Corresponding author. Tel.: +48 071 320 46 14; fax: +48 071 328 40 64. E-mail address: barbara.malinowska@pwr.wroc.pl (B. Malinowska). Tetrahedron Letters 51 (2010) 3406–3411 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet