Mendeleev Communications Electronic Version, Issue 4, 1998 (pp. 129–168) Synthesis of some novel water-soluble chiral phosphines Andrei A. Karasik,* Igor O. Georgiev, Roman I. Vasiliev and Oleg G. Sinyashin A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Centre of the Russian Academy of Sciences, 420088 Kazan, Russian Federation. Fax: +7 8432 75 2253; e-mail: karasik@glass.ksu.ras.ru Two individual (RR)- and (SS)-isomers of dipotassium 1,3-di[phenyl(carboxylato)methyl]-5-phenyl-1,3,5-diazaphosphorinane have been synthesized in the reaction of bis(hydroxymethyl)phenylphosphine, paraformaldehyde and the potassium salt of (R)- or (S)-a-phenylglycine.In the last decade a rapid development of catalytic reactions in aqueous/organic biphasic systems, especially enantioselective processes,1–3 has focused the attention of chemists on synthetic routes to the chiral water-soluble phosphine ligands.The functionalisation of well-known optically active phosphines: BINAP, BDPP, DIOP, CHIRAPHOS and cyclobutaneDIOP with highly polar sulfonate,4–6 carboxylate7,8 or ammonium9 groups is a general route to such compounds. Reactions of hydroxymethylphosphines with primary and secondary amines are a powerful method for constructing numerous classes of air-stable linear and cyclic aminomethylphosphine ligands.10–12 A number of water soluble13–14 and some optically active aminomethylphosphines10 have already been obtained.We suggest using the reactions of hydroxymethylphosphines with derivatives of amino acids to obtain water-soluble chiral heterocyclic phosphine precursors of catalysts for aqueous/ organic biphasic catalytic reactions.Amino acids have been used in the construction of chiral phosphine ligands as a source of asymmetric carbon atoms, but their highly polar carboxylic and amine groups have usually been displaced.15 Both enantiomers of amino acids are accessible. We now introduce the synthesis of two individual (RR)- and (SS)-isomers of dipotassium 1,3-di[phenyl(carboxylato)methyl]-5-phenyl-1,3,5- diazaphosphorinane 1.It has been shown in previous investigations that crystalline, air-stable, non bulky 1,3-di-R-5-phenyl-1,3,5-diazaphosphorinane ligands12 are obtained in high yields from bis(hydroxymethyl)- phenylphosphine, paraformaldehyde and primary aryl- or benzylamine in benzene or acetone.We used the potassium salt of (S)- or (R)-phenylglycine and methanol as a solvent in this reaction, because the reactivity of free amino acids in the nucleophilic substitution reactions are low due to their betaine structure and all reagents are soluble in methanol.† In both cases white, highly water soluble, crystalline compounds with identical physical characteristics‡ (except specific rotation) were obtained.The values of specific rotation ([a]20 546 ) for the isomers show that S-(+)- and R-(–)-amino acid salts give SS-(+)- and RR-(–)-isomers of phosphine, respectively. The IR spectra of the compounds exhibit absorption bands due to Ph and CO2 – groups and H2O. In the 31P NMR spectra only one signal shifted to higher fields corresponding to initial hydroxymethylphosphine was observed.The 31P NMR data show that one isomer of heterocyclic phosphine11 was formed. The 1H NMR data are not informative, because of the overlapping of the signals of methylene and methyne protons. The 13C NMR spectra are consistent with the structure of heterocyclic phosphine.16 In the 13C NMR spectra signals of two types of methylene groups from P–CH2–N and N–CH2–N fragments were recorded.The methylene carbon signal of the P–CH2–N fragment was located to low field and revealed the direct coupling constant 1JP–C. Only one asymmetric carbon atom signal was observed, confirming the formation of an individual enantiomer. The NMR data of the phosphine obtained, dissolved in water and methanol, are similar.(RR)- and (SS)-isomers of dipotassium 1,3-di[phenyl(carboxylato) methyl]-5-phenyl-1,3,5-diazaphosphorinane show high water solubility, and a 1 M solution in water can be obtained. This phosphine concentration in water is therefore in the range practical for catalytic applications. The authors are grateful for financial support of this work by INTAS (grant no. 93-2011-ext.). References 1 D. Sinou, Bull. Soc. Chim. Fr., 1987, 480. 2 V. V. Dunina and I. P. Beletskaya, Zh. Org. Khim., 1992, 28, 1929 (Russ. J. Org. Chem., 1992, 28, 1547). 3 V. V. Dunina and I. P. Beletskaya, Zh. Org. Khim., 1992, 28, 2368 (Russ. J. Org. Chem., 1992, 28, 1913). 4 F. Alario, Y. Amrani, Y. Colleuille, T. P. Dang, J. Jenck, D. Morel and D. Sinou, J. Chem. Soc., Chem.Commun., 1986, 202. † General procedure for the synthesis of (RR)- and (SS)-dipotassium 1,3-di[phenyl(carboxylato)methyl]-5-phenyl-1,3,5-diazaphosphorinanes. Paraformaldehyde (0.215 g, 7.2 mmol) was dissolved in bis(hydroxymethyl) phenyl phosphine (1.23 g, 7.2 mmol) with mild heating and the mixture was diluted with 5 ml of dry methanol. A solution of S-(+)- or R-(–)-a-phenylglycine (2.19 g, 14.5 mmol) and KOH (0.81 g, 14.5 mmol) in 10–15 ml methanol {[a]20 546 = ±125° for potassium salts (H2O, c = = 2.86)} was prepared separately. The two mixtures were combined at room temperature with good mixing.The mixture became absolutely transparent and was noticeably warm. After no later than 2 h the reaction mixture was filtered through filter paper and the filtrate was concentrated to about 3–4 ml.After 0.5–1 h the white fine solid which formed was filtered on a thick glass filter, washed twice with MeOH– Et2O (1:1), then Et2O, and dried in vacuo. The resulting white fine crystals are hygroscopic and decompose in air. ‡ (RR)- and (SS)-potassium 1,3-di[phenyl(carboxylato)methyl}-5-phenyl- 1,3,5-diazaphosphorinanes. Global yields about 75–80%, mp 244–246 °C (decomp.). 13C NMR (100.6 MHz, D2O) d: 48.72 (d, 2C, C*H, JCH 142.2 Hz), 72.26 (t, 1C, N–CH2–N, JCH 145.9 Hz), 74.11 (dt, 2C, P– CH2–N, JCH 135.9 Hz, JPC 74.37 Hz), 127.28 (d, 1C, P–C6H5-p, JCH 156.0 Hz), 128.04 (d, 2C, C*H–C6H5-p, JCH 161.0 Hz), 128.13 (d, 4C, C*H–C6H5–m, JCH 161.3 Hz), 128.30 (d, 4C, C*H–C6H5-o, JCH 161.0 Hz), 128.74 (s, 2C, C*H–C6H5-ipso), 128.76 (dd, 2C, P–C6H5-m, JCH 145.5 Hz, JPC 5.0 Hz), 130.79 (dd, 2C, P–C6H5-o, JCH 162.0 Hz, JPC 14.7 Hz), 137.74 (d, 1C, P–C6H5-ipso, JPC, 46.1 Hz), 177.97 (s, 2C, COOK); 31P NMR (162.5 MHz, MeOH) d: –59.84; 31P NMR (162.5 MHz, H2O) d: –60.35; IR (Nujol, KBr, n/cm–1) 1580 (CO), 1590 (Ph), 1620, 3300–3360 (H2O).[a]20 546: (RR) –38.8° (MeOH, c = 7.13), (RR) –107.8° (H2O, c = 7.15); (SS) +38.7° (MeOH, c = 7.15); (SS) +107.8° (H2O, c = 7.14).Found (%): C, 52.97; H, 4.92; N, 5.06; P, 5.24. Calc. for C25H27K2N2O6P (%): C, 53.57; H, 4.82; N, 5.00; P, 5.54. PhP OH OH Ph CO2 H2N H 2 K CH2 O N N P H Ph CO2 Ph CO2 H Ph MeOH 2K 2H2O 1Mendeleev Communications Electronic Version, Issue 4, 1998 (pp. 129-168) 5 W. A. Herrmann, G. P. Albanese, R. B. Manetsberger, P. Lappe and H.Bahrmann, Angew. Chem., Int. Ed. Engl., 1990, 29, 391. 6 Y. Amrani, L. Lecomte, D. Sinou, J. Bakos, I. Toth and B. Heil, Organometallics, 1989, 8, 542. 7 R. Benhamza, Y. Amrani and D. Sinou, J. Organomet. Chem., 1985, 288, C37. 8 T. Malmstrom and C. Andersson, J. Chem. Soc., Chem. Commun., 1996, 1135. 9 I. Toth and B. E. Hansson, Tetrahedron: Asymmetry, 1990, 1, 895. 10 K. Keller and A. Tzschach, Z. Chem., 1984, 24, 365. 11 B. A. Arbuzov and G. N. Nikonov, in Advances in Heterocyclic Chemistry, ed. A. R. Katritzky, Academic Press, New York, 1994, 61, 60. 12 A. A. Karasik and G. N. Nikonov, Zh. Obshch. Khim., 1993, 63, 1921 (Russ. J. Gen. Chem., 1993, 63, 2775). 13 T. Bartik, B. Bartik, I. P. Guo and B. E. Hanson, J. Organomet. Chem., 1994, 480, 15. 14 I. O. Georgiev, A. A. Karasik, F. F. Nigmadzyanov and G. N. Nikonov, Koord. Khim., 1995, 21, 210 (Russ. J. Coord. Chem., 1995, 21, 222). 15 H-U. Blaser, Chem. Rev., 1992, 92, 935. 16 V. A. Zagumennov, A. A. Karasik, E. V. Nikitin and G. N. Nikonov, Izv. Akad. Nauk, Ser. Khim., 1997, 1202 (Russ. Chem. Bull., 1997, 46, 1154). Received: Moscow, 14th May 1998 Cambridge, 18th June 1998; Com. 8/03648I