1,2,3,4,5,6-Hexahydrophosphinine 1-oxides with an exocyclic P-function at position 3: diastereoselective synthesis, stereostructure and conformation Gyo ¨rgy Keglevich, a, * Melinda Sipos, a Tama ´sKo ¨rtve ´lyesi, b Tı ´mea Imre c and La ´szlo ´T} oke a a Department of Organic Chemical Technology, Budapest University of Technology and Economics, 1521 Budapest, Hungary b University of Szeged, Department of Physical Chemistry, 6701 Szeged, Hungary c Hungarian Academy of Sciences, Chemical Research Center, 1525 Budapest, Hungary Received 17 November 2004; revised 5 January 2005; accepted 14 January 2005 Available online 29 January 2005 Abstract—Catalytic hydrogenation of the corresponding tetrahydrophosphinine oxides afforded the title compounds (4–6) as exclusive or major diastereomers the stereostructure and conformation of which were evaluated by stereospecific 3 J couplings, as well as HF/6-31G* ab initio calculations. Ó 2005 Elsevier Ltd. All rights reserved. The six-membered ring compounds, dihydro-, tetra- hydro- and hexahydrophosphinine oxides form a repre- sentative group of P-heterocycles. 1,2 We have recently introduced 1,2,3,6-tetrahydrophosphi- nine-derivatives with a P-function in position 3. 3 The dioxides and disulfides were found to exist as the twist-boat conformers stabilised by novel intramolecular interactions. 4 In addition, the corresponding diphos- phine behaved as a suitable bidentate P-ligand to form a cis-chelate platinum complex. 5 It was a logical continuation to prepare the fully satu- rated 3-substituted 1,2,3,4,5,6-hexahydrophosphinine oxides and to study their properties in comparison with the corresponding 1,2,3,6-tetrahydrophosphinine derivatives. The starting 3-diphenylphosphinoxido- and 3-dialkyl- phosphono-4-chloro-5-methyl-1,2,3,6-tetrahydrophosphi- nine oxides (1a, 2a,b and 3a,b) were subjected to catalytic hydrogenation to afford the corresponding 1,2,3,4,5,6-hexahydrophosphinine oxides 4a, 5a,b and 6a,b, respectively, in 83–92% yields after chromatogra- phy. 6 Saturation of the double bond and hydrogenolysis of the C–Cl bond took place under unusually mild con- ditions at 25–45 °C and ca. 3 bar, as compared to analo- gous cases. 7 Moreover, the reductions were stereoselective; the 1-phenylhexahydrophosphinine oxi- des 4a, 8 5a 9 and 6a 10 were formed as single diastereo- mers (Scheme 1), whereas the 1-ethoxy products 5b 11 and 6b 12 were obtained as mixtures of major (80%) and minor (20%) isomers (Scheme 2). The configura- tion at the P-1 and C-3 centres of the starting tetra- hydrophosphinine oxides 1–3 was assumed to have been preserved in the corresponding hexahydrophosphi- nine oxides 4–6, while the stereogenic sp 2 C-5 centre of 1–3 was transformed to an sp 3 carbon atom in a selective manner during the reduction. On the basis of the stereo- specific NMR couplings (see below), we had to assume 0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2005.01.073 Keywords: Phosphorus heterocycles; Hydrogenation; Stereoselection; Conformation. * Corresponding author. Tel.: +36 1 4631111x5883; fax: +36 1 4633648; e-mail: keglevich@mail.bme.hu P Ph CH 3 Z 2 P O 45 °C 3 bar H 2 Pd/C MeOH H H 1a 2a 3a Z 4a 5a 6a yield [%] Ph MeO EtO 92 90 85 O 1 2 3 4 5 6 P Ph Z 2 P O H O Cl CH 3 Scheme 1. Tetrahedron Letters 46 (2005) 1655–1658 Tetrahedron Letters