稀土金属化合物催化剂

7498 J. Org. Chem. 2010, 75, 7498–7501 Published on Web 10/06/2010 DOI: 10.1021/jo101743e r 2010 American Chemical Society pubs.acs.org/joc Lanthanide Amides [(Me3Si)2N]3Ln(μ-Cl)Li(THF)3 Catalyzed Hydrophosphonylation of Aryl Aldehydes Qingmao Wu, Jun Zhou, Zhigang Yao, Fan Xu,* and Qi Shen* Key Laboratory of Organic Synthesis, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China *xufan@suda.edu.cn;qshen@suda.edu.cn Received September 5, 2010 A highly efficient method for the synthesis of R-hydroxy phosphonates via lanthanide amides [(Me3Si)2N]3Ln- ( μ-Cl)Li(THF)3 catalyzed hydrophosphonylation of aro- matic aldehydes was developed. The reactions produced the products in excellent yields in the presence of 0.1 mol% [(Me3Si)2N]3La( μ-Cl)Li(THF)3 at room temperature with- in 5 min. The existence of LiCl in the catalyst was a key factor affecting the catalytic activity. Themechanism for the process of high efficiency was proposed. R-Hydroxy phosphonate exists as an important structural unit inmany biologically active compounds which have been widely used as pesticides, antibiotics, anticancer drugs, anti- viral agents, enzyme inhibitors, and so on.1 Alternative methods such as reduction of keto phosphonates,2 R-hydrox- ylation of alkyl phosphonates,3 and addition of trialkyl phosphites to aldehydes4 have been utilized for the synthesis of R-hydroxy phosphonates. Besides these pathways, the addition of dialkyl phosphites to aldehydes, known as the Pudovik reaction,5 is undoubtedly the most straightforward and atom-economical one toR-hydroxy phosphonates. How- ever, the Pudovik reaction cannot proceed spontaneously without heating in the absence of catalyst. Many research groups dedicated their efforts to develop highly active cata- lysts for this reaction in recent years. As a consequence, some catalysts or promoters, includingmetal oxides (such asMgO6 and Al2O3 7), Lewis bases8 (such as Et3N, 9 pyridine,10 and TMG11),Bronstedbases (suchasEtONa12 andTi(OiPr)4 13,7b), and some others (such as KF14 and MoO2Cl2 15), were found to be effective for this transformation. In addition, several examples of the reaction under thermal noncatalyzed conditions16 were also reported. It came to our notice that most of these systems require relatively harsh reaction condi- tions, such as high temperature (above 100 �C), long time (over 1 h), and/or high catalyst loading (more than 10mol%). Moreover, the yields were not always good and in some instances the target products may cleave and regenerate the starting raw materials.12,16b,17 More recently, to meet the growing demand for enantiomerically pure materials, the asymmetric synthesis of R-hydroxy phosphonates has been greatly developed18 while the methods reported for the (1) (a) Hilderbrand, R. L. The Role of Phosphonates in Living Systems; CRC: Boca Raton, FL, 1983. (b) Engel, R. Handbook of Organophosphorus Chemistry; Marcel Dekker: New York, 1992. (c) Szyma�nska, A.; Szymczak, M.; Boryski, J.; Stawi�nski, J.; Kraszewski, A.; Collu,G.; Sanna,G.;Giliberti, G.; Loddo, R.; Colla, P. L. Bioorg. Med. Chem. 2006, 14, 1924. (d) Shi, D.; Sheng, Z.; Liu, X.; Wu, H. Heteroatom Chem. 2003, 14, 266. (e) Ganzhorn, A. J.; Hoflack, J.; Pelton, P. D.; Strasser, F.; Chanal, M.; Piettre, S. R. Bioorg. Med. Chem. 1998, 6, 1865. (f) Frechette, R. F.; Ackerman, C.; Beers, S.; Look, R.; Moore J. Bioorg. Med. Chem. Lett. 1997, 7, 2169. (g) Patel, D. V.; Rielly-Gauvin, K.; Ryono, D. E.; Free, C. A.; Rogers, W. L.; Smith, S. A.; DeForrest, J. M.; Oehl, R. S.; Petrillo, E. W. J. Med. Chem. 1995, 38, 4557. (h) Stowasser, B.; Budt, K.; Jian-Qi, L.; Peyman, A.; Ruppert, D. Tetrahedron Lett. 1992, 33, 6625. (i) Patel, D. V.; Rielly-Gauvin, K.; Ryono, D. E. Tetrahedron Lett. 1990, 31, 5587. (2) (a) Zhang, W.; Shi, M. Chem. Commun. 2006, 1218. (b) Nesterov, V. V.; Kolodyazhnyi, O. I.Russ. J. Gen. Chem. 2006, 76, 1022. (c) Creary, X.; Geiger, C. C.; Hilton, K. J. Am. Chem. Soc. 1983, 105, 2851. (d) Nesterov, V. V.; Kolodyazhnyi, O. I. Tetrahedron: Asymmetry 2006, 17, 1023. (e) Nesterov, V. V.; Kolodyazhnyi, O. I. Russ. J. Gen. Chem. 2005, 75, 1161. (f) Meier, C.; Laux,W. H. G. Tetrahedron: Asymmetry 1995, 6, 1089. (g)Meier, C.; Laux, W. H. G.; Bats, J. W. Liebigs Ann. 1995, 1963. (h) Meier, C.; Laux, W.H.G.Tetrahedron 1996, 52, 589. (i)Meier, C.; Laux,W.H.G.; Bats, J.W. Tetrahedron: Asymmetry 1996, 7, 89. (j) Ord�o~nez, M.; de la Cruz, R.; Fern�andez-Zertuche, M. M.; Mu~noz-Hern�adez, M. A. Tetrahedron: Asym- metry 2002, 13, 559. (3) (a) Cristau, H.; Pirat, J.; Drag, M.; Kafarski, P. Tetrahedron Lett. 2000, 41, 9781. (b) Pogatchnik, D.M.;Wiemer, D. F.TetrahedronLett. 1997, 38, 3495. (c) Skropeta, D.; Schmidt, R. R.Tetrahedron: Asymmetry 2003, 14, 265. (4) (a)Nakanishi, K.;Kotani, S.; Sugiura,M.;Nakajima,M.Tetrahedron 2008, 64, 6415. (b) Azizi, N.; Saidi, M. R. Phosphorus, Sulfur Silicon Relat. Elem. 2003, 178, 1255. (c) Heydari, A.; Arefi, A.; Khaksar, S.; Tajbakhsh,M. Catal. Commun. 2006, 7, 982. (d) Goldeman,W.; Soroka,M. Synthesis 2006, 3019. (e) Thottempudi, V.; Chung, K. Bull. Korean Chem. Soc. 2008, 29, 1781. (5) Pudovik, A. N.; Konovalova, I. V. Synthesis 1979, 81. (6) (a) Kaboudin, B. Tetrahedron Lett. 2003, 44, 1051. (b) Kaboudin, B. Tetrahedron Lett. 2000, 41, 3169. (7) (a) Texier-Boullet, F.; Foucaud, A. Synthesis 1982, 916. (b) Jung, M. E.; Cordova, J.; Murakami, M. Org. Lett. 2009, 11, 3882. (8) (a) Kaim, L. E.; Gaultier, L.; Grimaud, L.; Santos, A.D. Synlett 2005, 2335. (b) Gancarz, R. Tetrahedron 1995, 51, 10627. (9) (a) Taylor, W. P.; Zhang, Z.; Widlanski, T. S. Bioorg. Med. Chem. 1996, 4, 1515. (b) Cristau, H.; Pirat, J.; Virieux, D.;Monbrun, J.; Ciptadi, C.; Bekro, Y. J. Organomet. Chem. 2005, 690, 2472. (10) Li, C.; Yuan, C. Tetrahedron Lett. 1993, 34, 1515. (11) (a) Simoni, D.; Rondanin, R.;Morini, M.; Baruchello, R.; Invidiata, F. P. Tetrahedron Lett. 2000, 41, 1607. (b) Simoni, D.; Invidiata, F. P.; Manferdini, M.; Lampronti, I.; Rondanin, R.; Roberti, M.; Pollini, G. P. Tetrahedron Lett. 1998, 39, 7615. (12) Keglevich, G.; Sipos, M.; Takacs, D.; Greiner, I.Heteroatom Chem. 2007, 18, 226. (13) Yokomatsu, T.; Yamagishi, T.; Shibuya, S. J. Chem. Soc., Perkin Trans. 1 1997, 1527. (14) (a) Texier-Boullet, F.; Foucaud, A. Synthesis 1982, 2, 165. (b) Li, Z.; Sun, H.;Wang, Q.; Huang, R.Heteroatom Chem. 2003, 14, 384. (c) Villemin, D.; Racha, R. Tetrahedron Lett. 1986, 27, 1789. (d) Sebti, S.; Rhihil, A.; Saber, A.; Laghrissi, M.; Boulaajaj, S. Tetrahedron Lett. 1996, 37, 3999. (15) de Noronha, R. G.; Costa, P. J.; Romao, C. C.; Calhorda, M. J.; Fernandes, A. C. Organometallics 2009, 28, 6206. (16) (a) Tsai, H.; Lin, K.; Ting, T.; Burton, D. J. Helv. Chim. Acta 1999, 82, 2231. (b)Kharasch,M. S.;Mosher, R.A.; Bengelsdorf, I. S. J.Org. Chem. 1960, 25, 1000. (17) Gancarz, R.; Gancarz, I.; Walkowiak, U. Phosphorus, Sulfur Silicon Relat. Elem. 1995, 104, 45. TK Highlight TK Highlight TK Typewriter 芳香的 TK Typewriter 醛 TK Typewriter TK Typewriter 这一反应有一个很 好的产率，在室温下， 加0.1mol的催化剂 ，在五分钟内可以 反应完成 TK Typewriter TK Typewriter 氯化锂在催化剂中 对催化剂活性的影响 起着很重要的作用 TK Typewriter 杀虫 TK Typewriter 酶 TK Typewriter 抑制剂 TK Typewriter 减少 TK Typewriter 烷基 TK Typewriter 加上 TK Typewriter 三烷基 TK Typewriter 醛 TK Highlight TK Typewriter 自发地 TK Typewriter TK Arrow TK Typewriter 嘧啶 TK Typewriter 热力学的 TK Highlight TK Highlight TK Arrow TK Typewriter 苛刻的反应条件 TK Typewriter 裂开 TK Highlight TK Arrow TK Typewriter 不对称合成 J. Org. Chem. Vol. 75, No. 21, 2010 7499 Wu et al. JOCNote stereoselective hydrophosphonylation of aldehydes usually involve high catalyst loading. Therefore, the further develop- ment of novel catalysts and relevant processes of high efficiency for the synthesis of R-hydroxy phosphonate as valuable small molecule still remains of great interest. Homoleptic bis(trimethylsilyl)amides of lanthanides Ln[N(SiMe3)2]3 19 have been found to be efficient catalysts for a series of intermolecular or intramolecular reactions, including the Tishchenko reaction,20 amidation,21 monoad- dition of terminal alkynes to nitriles,22 coupling reaction of isocyanides with terminal alkynes,23 and dimerization of terminal alkynes.24 They also show high activity as catalysts for versatile hydroelementation processes such as hydrosilyla- tion,25 hydroboration,26 hydroamination,20b,27 hydrophos- phination,28 and hydroalkoxylation.29 The tetracoordinate lanthanide amides [(Me3Si)2N]3Ln( μ-Cl)Li(THF)3, 30 a chloride-bridged “ate” complex derived from Ln[N(SiMe3)2]3, also work well as catalysts for aldol condensation,31 MMA polymerization,30c,d aza-Henry reaction,32 and guanylation of amines.33 Although [(Me3Si)2N]3Ln(μ-Cl)Li(THF)3 is more readily available than Ln[N(SiMe3)2]3 from the viewpoint of the syntheticmethod, the applicationof the former as an efficient catalyst is comparatively limited. In some instances reported, the catalytic activities of the tricoordinate Ln[N(SiMe3)2]3 and tetracoordinate [(Me3Si)2N]3Ln(μ-Cl)Li(THF)3 were com- pared with each other. The results indicated that the existence of LiCl in [(Me3Si)2N]3Ln( μ-Cl)Li(THF)3 may sometimes 31,32 improve the activity of Ln[N(SiMe3)2]3 while at other times 33 produce the opposite effect. In continuation of our previous studies on lanthanide- catalyzed carbon-nitrogen bond-forming reactions,34 we investigated the effectiveness of lanthanide amides as cata- lysts for the carbon-phosphorus bond-forming reactions. Herein, the paper presents a highly efficient process afford- ing R-hydroxy phosphonates by the lanthanide amides- catalyzed Pudovik reaction. The addition of diethyl phosphite to benzaldehyde to afford diethyl [hydroxy(phenyl)methyl]phosphonate was used as themodel reaction in our initial screening of potential lanthanide catalysts. As shown inTable 1, typical Lewis acid- type compounds such as lanthanum trihalides (LaX3, X = Cl, Br, I) and ytterbium triflate [Yb(OTf)3] cannot initiate the reaction with the catalyst loading of 20 mol % (entries 1-4), indicating that the Lewis acidity of the lanthanide compounds was not decisive in catalyzing this reaction. In strong contrast, homoleptic lanthanum amide La[N(SiMe3)2]3 catalyzed the reaction with high efficiency. The product was obtained in 63%yieldwith 0.5mol%La[N(SiMe3)2]3 at 25 �C for 5min (entry 5). However, no desired product was observed when the catalyst loadingwasdecreased to 0.1mol%(entry 6). To our delight, the tetracoordinate lanthanum amide [(Me3Si)2N]3La( μ-Cl)Li(THF)3 exhibited the catalytic activ- ity that was still superior to that of tricoordinate lanthanum amide La[N(SiMe3)2]3. The utility of 0.5 mol % of [(Me3Si)2- N]3La( μ-Cl)Li(THF)3 gave the product in an excellent 96% yield within 5min (entry 7). Optimization studies revealed that decreasing the catalyst loading to 0.1 mol % kept the yield at 92% (entry 8). Further decreased catalyst loading of 0.05 mol % led to a dramatically lowered yield of 43% (entry 9). Because [(Me3Si)2N]3La(μ-Cl)Li(THF)3 can be regarded as a solvated adduct of La[N(SiMe3)2]3 andLiCl, anhydrous LiCl was tried alone to verify whether it can act as a catalyst inde- pendently. No product was detected after 48 h (entry 10). Besides, the use of the mixture of La[N(SiMe3)2]3 and TABLE 1. Catalysts Screening for the Reaction of Benzaldehyde with Diethyl Phosphitea entry catalyst loading (mol %) time yield (%) 1 LaCl3 2.0 12 h 0 2 LaBr3 2.0 12 h 0 3 LaI3 2.0 12 h 0 4 Yb(OTf)3 2.0 6 h 0 5 La[N(SiMe3)2]3 0.5 5 min 63 6 La[N(SiMe3)2]3 0.1 5 min 0 7 [(Me3Si)2N]3La(μ-Cl)Li(THF)3 0.5 5 min 96 8 [(Me3Si)2N]3La(μ-Cl)Li(THF)3 0.1 5 min 92 9 [(Me3Si)2N]3La(μ-Cl)Li(THF)3 0.05 5 min 43 10 LiCl 1.0 48 h 0 aReactions were performed with 1 mmol of PhCHO and 1.2 mmol of HOP(OEt)2 in 1 mL of toluene at 25 �C. (18) (a)Merino, P.;Marqu�es-L�opez, E.; Herrera, R. P.Adv. Synth. Catal. 2008, 350, 1195. (b) Yang, F.; Zhao, D.; Lan, J.; Xi, P.; Yang, L.; Xiang, S.; You, J. Angew. Chem., Int. Ed. 2008, 47, 5646. (c) Suyama, K.; Sakai, Y.; Matsumoto, K.; Saito, B.; Katsuki, T.Angew. Chem., Int. Ed. 2009, 48, 1. (d) Abell, J. P.; Yamamoto, H. J. Am. Chem. Soc. 2008, 130, 10521. (e) Uraguchi, D.; Ito, T.; Ooi, T. J. Am. Chem. Soc. 2009, 131, 3836. (19) (a) Schuetz, S. A.; Day, V. W.; Sommer, R. D.; Rheingold, A. L.; Belot, J. A. Inorg. Chem. 2001, 40, 5292. (b) Bradley, D. C.; Ghotra, J. S.; Hart, F.A. J. Chem. Soc., DaltonTrans. 1973, 1021. (c) Alyea, E. C.; Bradley, D. C.; Copperthwaite, R. G. J. Chem. Soc., Dalton Trans. 1972, 1580. (d) Andersen, R. A.; Templeton, D. H.; Zalkin, A. Inorg. Chem. 1978, 17, 2317. (e) Brady, E. D.; Clark, D. L.; Gordon, J. C.; Hay, P. J.; Keogh, D.W.; Poli, R.; Scott, B. L.; Watkin, J. G. Inorg. Chem. 2003, 42, 6682. (20) (a) Berberich, H.; Roesky, P. W. Angew. Chem., Int. Ed. 1998, 37, 1569. (b) B€urgstein, M. R.; Berberich, H.; Roesky, P. W. Chem.;Eur. J. 2001, 7, 3078. (c) Chen, Y.; Zhu, Z.; Zhang, J.; Shen, J.; Zhou, X. J. Organomet. Chem. 2005, 690, 3783. (21) Seo, S.; Marks, T. J. Org. Lett. 2008, 10, 317. (22) Shen, Q.; Huang, W.; Wang, J.; Zhou, X. Organometallics 2008, 27, 301. (23) (a) Komeyama, K.; Sasayama, D.; Kawabata, T.; Takehira, K.; Takaki, K. Chem. Commun. 2005, 634. (b) Komeyama, K.; Sasayama, D.; Kawabata, T.; Takehira, K.; Takaki, K. J. Org. Chem. 2005, 70, 10679. (24) (a) Komeyama, K.; Kawabata, T.; Takehira, K.; Takaki, K. J. Org. Chem. 2005, 70, 7260. (b)Nishiura,M.; Hou, Z.;Wakatsuki, Y.; Yamaki, T.; Miyamoto, T. J. Am. Chem. Soc. 2003, 125, 1184. (c) Komeyama, K.; Takehira, K.; Takaki, K. Synthesis 2004, 1062. (25) Horino, Y.; Livinghouse, T. Organometallics 2004, 23, 12. (26) Horino, Y.; Livinghouse, T.; Stan, M. Synlett 2004, 2639. (27) (a) Hong, S.; Marks, T. J. Acc. Chem. Res. 2004, 37, 673. (b) Kim, Y. K.; Livinghouse, T.; Bercaw, J. E. Tetrahedron Lett. 2001, 42, 2933. (c) Kim, Y. K.; Livinghouse, T.; Horino, Y. J. Am. Chem. Soc. 2003, 125, 9560. (d) Kim, Y. K.; Livinghouse, T. Angew. Chem., Int. Ed. 2002, 41, 3645. (28) Kawaoka, A. M.; Douglass, M. R.; Marks, T. J. Organometallics 2003, 22, 4630. (29) (a) Yu, X.; Seo, S.; Marks, T. J. J. Am. Chem. Soc. 2007, 129, 7244. (b) Seo, S.; Yu, X.; Marks, T. J. J. Am. Chem. Soc. 2009, 131, 263. (30) (a) Westerhausen, M.; Hartmann, M.; Pfitzner, A.; Schwarz, W. Z. Anorg. Allg. Chem. 1995, 621, 837. (b) Edelmann, F. T.; Steiner, A.; Stalke, D. Polyhedron 1994, 13, 539. (c) Zhou, S.; Wang, S.; Yang, G.; Liu, X.; Sheng, E.; Zhang, K.; Cheng, L.; Huang, Z. Polyhedron 2003, 22, 1019. (d) Xie, M.; Liu, X.; Wang, S.; Liu, L.; Wu, Y.; Yang, G.; Zhou, S.; Sheng, E.; Huang, Z. Chin. J. Chem. 2004, 22, 678. (e) Sheng, E.; Wang, S.; Yang, G.; Zhou, S.; Cheng, L.; Zhang, K.; Huang, Z. Organometallics 2003, 22, 684. (31) Zhang, L.; Wang, S.; Sheng, E.; Zhou, S. Green Chem. 2005, 7, 683. (32) Zhang, L.; Wu, H.; Su, S.; Wang, S. Chin. J. Chem. 2009, 27, 2061. (33) Li, Q.; Wang, S.; Zhou, S.; Yang, G.; Zhu, X.; Liu, Y. J. Org. Chem. 2007, 72, 6763. (34) (a) Xu, F.; Luo, Y.; Deng, M.; Shen, Q. Eur. J. Org. Chem. 2003, 4728. (b) Zhou, Z.; Xu, F.; Han, X.; Zhou, J.; Shen, Q. Eur. J. Org. Chem. 2007, 5265. (c) Han, X.; Xu, F.; Luo, Y.; Shen, Q. Eur. J. Org. Chem. 2005, 1500. (d) Zhang, H.; Zhou, Z.; Yao, Z.; Xu, F.; Shen, Q. Tetrahedron Lett. 2009, 50, 1622. TK Typewriter 立体选择性 TK Typewriter 有关的 TK Typewriter TK Typewriter 二（三甲基硅基）胺 TK Typewriter 分子间的和分子 内的反应 TK Highlight TK Typewriter 睛 7500 J. Org. Chem. Vol. 75, No. 21, 2010 JOCNote Wu et al. anhydrous LiCl in 1:1 ratio in THF as catalyst failed to produce the same effect with [(Me3Si)2N]3La(μ-Cl)Li- (THF)3. The result indicated that the combination manner of La[N(SiMe3)2]3 with LiCl in crystalline [(Me3Si)2N]3- La( μ-Cl)Li(THF)3 may be a key factor affecting its cata- lytic ability. Then, the reaction conditions were selected as 0.1 mol % of [(Me3Si)2N]3Ln(μ-Cl)Li(THF)3 at 25 �C for 5 min for the following studies. Next, a series of lanthanide amides were used to assess the influence of central metal on the activity and the results are shown in Table 2. It was found that the decrease in the Ln(III) ionic radii from the light rare earth La to heavy rare earth Er andY has little influence on the reaction and the high yields above 90% were obtained. When [(Me3Si)2N]3Yb(μ-Cl)- Li(THF)3 was used, a slightly decreased yield of 82% was observed. So, the amide complexofLa, the largestmetal among those tested, was chosen as a representative lanthanide source for carrying out the following studies. Considering the obvious difference in the activity pre- sented between La[N(SiMe3)2]3 and [(Me3Si)2N]3La( μ-Cl)- Li(THF)3, a new question arose if LiCl is the best partner of La[N(SiMe3)2]3 in improving the activity. It was known that [(Me3Si)2N]3Ln( μ-Cl)Li(THF)3 can be formed in situ by the metathesis reaction of LnCl3 with 3 equiv of LiN(SiMe3)2 in THF.30c-e To learn more about the influence of alkali metal ion and halide ion on the reaction, themodel reaction with in situ formed tetracoordinate lanthanumamides, generated by the reaction of lanthanum trihalides with silylamides of sodium or lithium, as catalysts was performed. The results are presented in Table 3. As we expected, the in situ formed [(Me3Si)2N]3La( μ-Cl)Li(THF)3 showed the same activity as that of prepared [(Me3Si)2N]3La( μ-Cl)Li(THF)3 under the standard reaction conditions. However, either changing Cl to Br and I or changing Li to Na led to a decrease of the yield. For example, the utility of LaI3 instead of LaCl3 gave a yield of 14% (entry 3) while using NaN(SiMe3)2 instead of LiN(SiMe3)2 provided an 18% yield (entry 4). The catalyst generated from NaN(SiMe3)2 and LaI3 failed to give the desired product (entry 5). With the optimum reaction conditions in hand, the scope of the reaction was explored to various aromatic aldehydes and dialkyl phosphites. As shown in Table 4, all the reactions proceeded smoothly and quickly affording the correspond- ing R-hydroxy phosphonates in excellent yields (91-97%) at room temperature within 5min. The reactionwas general for aromatic aldehydes bearing substitutions at ortho-, meta-, and para-positions and tolerates both electron-deficient aldehydes and those that are electron rich. Heteroatoms either in the functional groups of the benzene ring or in heteroaromatics such as furan had no influence on the reaction. Dialkyl phosphites with different steric hindrances underwent the reaction giving the yields with little difference. The results suggest that [(Me3Si)2N]3La( μ-Cl)Li(THF)3 is highly active in catalyzing the hydrophosphonylation of aromatic aldehydes, regardless of electronic effects or steric effects of the substrates. According to the distinctive properties of lanthanide amides, the proposedmechanism (Scheme 1) for the Pudovik reaction may involve rapid deprotonation of the dialkyl phosphite, which may exist in its tautomeric form as the phosphonate, releasing amine and forming the intermediate 5, which is most probably the catalytically active species. 5 then reacts as a nucleophile toward the carbonyl carbon atoms of the aldehyde to generate the target R-hydroxy phosphonate. The superiority in the catalytic ability of [(Me3Si)2N]3- Ln(μ-Cl)Li(THF)3 over Ln[N(SiMe3)2]3 may be accounted for by two possibilities. First, it has been found that the Ln-N bond lengths in [(Me3Si)2N]3Ln(μ-Cl)Li(THF)3 are longer than those found in Ln[N(SiMe3)2]3. For example, the average Nd-N bond distance of 2.336 A˚30b in [(Me3Si)2N]3Nd- ( μ-Cl)Li(THF)3 is longer than the Nd-N bond length of 2.29 A˚19d found in Nd[N(SiMe3)2]3, and the average Sm-N TABLE 2. The Influence of Lanthanide Metal on the Reactiona Ln = Y La Nd Sm Er Yb yield (%) 93 93 94 92 90 82 aReactions were performed with 1 mmol of PhCHO and 1.2 mmol of HOP(OEt)2 in 1 mL of toluene at 25 �C for 5 min. TABLE 3. The Influence of Alkali Metals and Halogens on the React