Development of chiral (S)-prolinol-derived ligands for palladium-catalyzed asymmetric allylic alkylation: Effect of a siloxymethyl group on the pyrrolidine backbone

Article abstract of DOI:10.1021/jo049469t

A series of novel chiral aminophosphine ligands are designed and readily prepared from (S)-prolinol. The reactivity and selectivity in the palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate with a dimethyl malonate-BSA-Li

Full text of DOI:10.1021/jo049469t

Develop m en t of Ch ir a l (S)-P r olin ol-Der ived Liga n d s for
P a lla d iu m -Ca ta lyzed Asym m etr ic Allylic Alk yla tion : Effect of a
Siloxym eth yl Gr ou p on th e P yr r olid in e Ba ck bon e
Youichi Tanaka, Takashi Mino,* Koji Akita, Masami Sakamoto, and Tsutomu Fujita
Department of Materials Technology, Faculty of Engineering, Chiba University, 1-33, Yayoi-cho,
Inage-ku, Chiba 263-8522, J apan
tmino@faculty.chiba-u.jp
Received March 31, 2004
A series of novel chiral aminophosphine ligands are designed and readily prepared from (S)-prolinol.
The reactivity and selectivity in the palladium-catalyzed asymmetric allylic alkylation of 1,3-
diphenyl-2-propenyl acetate with a dimethyl malonate-BSA-LiOAc system using these chiral
ligands are evaluated, and the structural elucidation of ligands and palladium complex is also
conducted. Moreover, a series of trialkylsilylated chiral aminophosphine ligands are prepared and
applied to palladium-catalyzed asymmetric allylic alkylation (up to 98% ee).
In tr od u ction
have reported palladium-catalyzed asymmetric allylic
alkylation using pyrrolidinyl-containing chiral amino-
phosphines 3 as a ligand.14 It has been proved that a
series of aminophosphine ligands 3 possessing methoxyl
groups in the terminal of the side chain induced high
enantioselectivities. Herein, we report palladium-cata-
lyzed asymmetric allylic alkylation using novel pyrro-
lidinyl-containing chiral aminophosphine ligands (S)-415
possessing hydroxyl groups in the terminal of the side
chain.
In recent years, palladium-catalyzed allylic alkylation
has been extended to catalytic asymmetric synthesis by
the use of chiral ligands,1 and the development of highly
efficient enantioselective catalysis for this reaction has
been awaited with great anticipation.2 Because chiral
phosphine ligands can induce a high enantiomeric excess
in the palladium-catalyzed reaction of racemic and
achiral allylic substrates with nucleophiles, P,P-chelate
chiral ligands such as BINAP,3 chiraphos,4 and Trost’s
ligand5 play an important role in catalytic asymmetric
synthesis.6 Chiral P,N-chelate compounds have also been
used as ligands for asymmetric allylic alkylation during
the past decades,6t,7 for instance, phosphinooxazolines,8
iminophosphines,9 phosphinohydrazones10 (possessing sp2
nitrogen11), and aminophosphines6c,d,f,12 (possessing sp3
nitrogen). In particular, pyrrolidinyl-containing amino-
phosphines13 such as 113h and 213d,g,m,14b (Figure 1) have
been found to be efficient chiral sources. Recently, we
(6) Some recent examples of Pd-catalyzed AAA reaction using P,P-
chelate ligands: (a) Chen, X.; Guo, R.; Li, Y.; Chen, G.; Yeung, C.-H.;
Chan, A. S. C. Tetrahedron: Asymmetry 2004, 15, 213. (b) Oohara,
N.; Katagiri, K.; Imamoto, T. Tetrahedron: Asymmetry 2003, 14, 2171.
(c) Dell’Anna, M. M.; Mastrilli, P.; Nobile, C. F.; Suranna, G. P. J . Mol.
Catal. A 2003, 201, 131. (d) Zhao, D.; Ding, K. Org. Lett. 2003, 5, 1349.
(e) Sinou, D.; Rabeyrin, C.; Nguefack, C. Adv. Synth. Catal. 2003, 345,
357. (f) Vasse, J .-L.; Stranne, R.; Zalubovskis, R.; Gayet, C.; Moberg,
C. J . Org. Chem. 2003, 68, 3258. (g) Ohta, T.; Sasayama, H.; Nakajima,
O.; Kurahashi, N.; Fujii, T.; Furukawa, I. Tetrahedron: Asymmetry
2003, 14, 537. (h) Lotz, M.; Kramer, G.; Knochel, P. Chem. Commun.
2002, 2546. (i) Frison, G.; Brebion, F.; Dupont, R.; Mercier, A.; Ricard,
L.; Mathey, F. C. R. Acad. Sci., Ser. IIc: Chim. 2002, 5, 245. (j) Lee,
S.; Koh, J . H.; Park, J . J . Organomet. Chem. 2001, 637-639, 99. (k)
Pa`mies, O.; van Strijdonck, G. P. F.; Die´guez, M.; Deerenberg, S.; Net,
G.; Ruiz, A.; Claver, C.; Kamer, P. C. J .; van Leeuwen, P. W. N. M. J .
Org. Chem. 2001, 66, 8867. (l) Zhang, R.; Yu, L.: Xu, L.; Wang, Z.;
Ding, K. Tetrahedron Lett. 2001, 42, 7659. (m) Ogasawara, M.; Yoshida,
K.; Hayashi, T. Organometallics 2001, 20, 3913. (n) Tissot, O.;
Gouygou, M.; Dallemer, F.; Daran, J .-C.; Balavoine, G. G. A. Angew.
Chem., Int. Ed. 2001, 40, 1076. (o) Kang, J .; Lee, J . H.; Choi, J . S.
Tetrahedron: Asymmetry 2001, 12, 33. (p) Nettekoven, U.; Widhalm,
M.; Kalchhauser, H.; Kamer, P. C. J .; van Leeuwen, P. W. N. M.; Lutz,
M.; Spek, A. L. J . Org. Chem. 2001, 66, 759. (q) Saitoh, A.; Uda, T.;
Morimoto, T. Tetrahedron: Asymmetry 2000, 11, 4049. (r) Argouarch,
G.; Samuel, O.; Riant, O.; Daran, J .-C.; Kagan, H. B. Eur. J . Org. Chem.
2000, 2885. (s) Gladiali, S.; Dore, A.; Fabbri, D.; Medici, S.; Rirri, G.;
Pulacchini, S. Eur. J . Org. Chem. 2000, 2861. (t) Arena, C. G.; Drommi,
D.; Faraone, F. Tetrahedron: Asymmetry 2000, 11, 2765. (u) Reetz,
M. T.; Sostmann, S. J . Organomet. Chem. 2000, 603, 105. (v) Yan, Y.;
RajanBabu, T. V. Org. Lett. 2000, 2, 199. (w) Breeden, S.; Wills, M. J .
Org. Chem. 1999, 64, 9735. (x) Fuji, K.; Kinoshita, N.; Tanaka, K.
Chem. Commun. 1999, 1895. (y) Yan, Y.-Y.; Widhalm, M. Monatsh.
Chem. 1999, 130, 873. (z) Zhang, W.; Shimanuki, T.; Kida, T.;
Nakatsuji, Y.; Ikeda, I. J . Org. Chem. 1999, 64, 6247.
* To whom correspondence should be addressed. Tel: +81-43-290-
3385. Fax: +81-43-290-3401.
(1) (a) Tsuji, J .; Minami, I. Acc. Chem. Res. 1987, 20, 140. (b) Trost,
B. M.; Verhoeven, T. R. In Comprehensive Organometallic Chemistry;
Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds.; Pergamon: Oxford,
1982; Vol. 8, p 799. (c) Trost, B. M. Acc. Chem. Res. 1980, 13, 385.
(2) (a) Trost, B. M. Chem. Pharm. Bull. 2002, 50, 1. (b) Trost, B.
M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921. (c) Trost, B. M.; Lee,
C. In Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; VCH
Publishers: New York, 2000; p 893. (d) Williams, J . M. J . Synlett 1996,
705. (e) Pfaltz, A.; Lautens, M. In Comprehensive Asymmetric Catalysis;
J acobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer-Verlag: New
York, 1999; Chapter 24. (f) Trost, B. M.; Van Vranken, D. L. Chem.
Rev. 1996, 96, 395. (g) Pfaltz, A. Acc. Chem. Res. 1993, 26, 339. (h)
Hayashi, T. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH
Publishers: New York, 1993; p 325. (i) Consiglio, G.; Waymouth, R.
M. Chem. Rev. 1989, 89, 275.
(3) Brown, J . M.; Hulmes, D. I.; Guiry, P. J . Tetrahedron 1994, 50,
4493.
(4) Yamaguchi, M.; Shima, T.; Yamagishi, T.; Hida, M. Tetrahe-
dron: Asymmetry 1991, 2, 663.
(5) Trost, B. M.; Bunt, R. C. J . Am. Chem. Soc. 1994, 116, 4089.
10.1021/jo049469t CCC: $27.50 © 2004 American Chemical Society
Published on Web 09/04/2004
J . Org. Chem. 2004, 69, 6679-6687
6679

Tanaka et al.
Resu lts a n d Discu ssion
Syn th esis of Ch ir a l Am in op h osp h in e Liga n d s (S)-
4. The chiral aminophosphine ligands (S)-4 were readily
prepared from commercially available optically pure (S)-
(7) Some recent examples of Pd-catalyzed AAA reaction using P,N-
chelate ligands: (a) Clayden, J . Chem. Commun. 2004, 127. (b) Rahm,
F.; Fischer, A.; Moberg, C. Eur. J . Org. Chem. 2003, 2839. (c) Gladiali,
S.; Loriga, G.; Medici, S.; Taras, R. J . Mol. Catal. A 2003, 196, 27. (d)
Chen, G.; Li, X.; Zhang, H.; Gong, L.; Mi, A.; Cui, X.; J iang, Y.; Choi,
M. C. K.; Chan, A. S. C. Tetrahedron: Asymmetry 2002, 13, 809. (e)
Polosukhin, A. I.; Bondarev, O. G.; Korostylev, A. V.; Hilgraf, R.;
Davankov, V. A.; Gavrilov, K. N. Inorg. Chim. Acta 2001, 323, 55. (f)
J ones, G.; Richards, C. J . Tetrahedron Lett. 2001, 42, 5553. (g)
Delapierre, G.; Brunel, J . M.; Constantieux, T.; Buono, G. Tetrahe-
dron: Asymmetry 2001, 12, 1345. (h) Clayden, J .; Lai, L. W.; Helliwell,
M. Tetrahedron: Asymmetry 2001, 12, 695. (i) Mino, T.; Kashihara,
K.; Yamashita, M. Tetrahedron: Asymmetry 2001, 12, 287. (j) Zhang,
A.; Feng, Y.; J iang, B. Tetrahedron: Asymmetry 2000, 11, 3123. (k)
Hashizume, T.; Yonehara, K.; Mori, K.; Ohe, K.; Uemura, S. J . Org.
Chem. 2000, 65, 5197. (l) Yonehara, K.; Hashizume, T.; Mori, K.; Ohe,
K.; Uemura, S. J . Org. Chem. 1999, 64, 9374. (m) Hilgraf, R.; Pfaltz,
A. Synlett 1999, 1814. (n) Brunel, J . M.; Constantieux, T.; Buono, G.
J . Org. Chem. 1999, 64, 8940. (o) Yonehara, K.; Hashizume, T.; Mori,
K.; Ohe, K.; Uemura, S. Chem. Commun. 1999, 415. (p) Dai, X.; Virgil,
S. Tetrahedron Lett. 1999, 40, 1245.
F IGURE 1. Pyrrolidinyl-containing aminophosphines.
prolinol and various phosphine oxides 5 in two steps
(Scheme 1). A nucleophilic aromatic substitution (SNAr)
reaction16 of a phosphine oxide compound such as di-
phenyl(2-methoxyphenyl)phosphine oxide 5a with bis-
lithiated (S)-prolinol gave the corresponding aminophos-
phine oxide 6a . This aminophosphine oxide 6a was
converted into the desired chiral aminophosphine ligand
(S)-4a in good yield by reduction with trichlorosilane-
triethylamine. The other ligands (S)-4 were prepared in
the same manner.
(8) (a) Fache, F.; Schulz, E.; Tommasino, M. L.; Lemaire, M. Chem.
Rev. 2000, 100, 2159. (b) Helmchen, G. J . Organomet. Chem. 1999,
576, 203. (c) Dawson, J . G.; Frost, C. G.; Williams, J . M. J .; Coote, S.
J . Tetrahedron Lett. 1993, 34, 3149. (d) von Matt, P.; Pfaltz, A. Angew.
Chem., Int. Ed. Engl. 1993, 32, 566. (e) Sprinz, J .; Helmchen, G.
Tetrahedron Lett. 1993, 34, 1769. Some recent examples of Pd-
catalyzed AAA reaction using phosphinooxazoline ligands: (f) Danjo,
H.; Higuchi, M.; Yada, M.; Imamoto, T. Tetrahedron Lett. 2004, 45,
603. (g) Blanc, C.; Hannedouche, J .; Agbossou-Niedercorn, F. Tetra-
hedron Lett. 2003, 44, 6469. (h) Bolm, C.; Xiao, L.; Kesselgruber, M.
Org. Biomol. Chem. 2003, 1, 145. (i) Wu, X.-W.; Yuan, K.; Sun, W.;
Zhang, M.-J .; Hou, X.-L. Tetrahedron: Asymmetry 2003, 14, 107. (j)
Tietze, L.; Lohmann, J . K. Synlett 2002, 2083. (k) Moreno, R. M.;
Bueno, A.; Moyano, A. M. J . Organomet. Chem. 2002, 660, 62. (l)
Zehnder, M.; Schaffner, S.; Neuburger, M.; Plattner, D. A. Inorg. Chim.
Acta 2002, 337, 287. (m) You, S.-L.; Hou, X.-L.; Dai, L.-X.; Yu, Y.-H.;
Xia, W. J . Org. Chem. 2002, 67, 4684. (n) Xu, G.; Gilbertson, S. R.
Tetrahedron Lett. 2002, 43, 2811. (o) Patti, A.; Lotz, M.; Knochel, P.
Tetrahedron: Asymmetry 2002, 12, 3375. (p) Gilbertson, S. R.; Xie,
D.; Fu, Z. J . Org. Chem. 2001, 66, 7240. (q) Cozzi, P. G.; Zimmermann,
N.; Hilgraf, R.; Schaffner, S.; Pfaltz, A. Adv. Synth. Catal. 2001, 343,
450. (r) Deng, W.-P.; You, S.-L.; Hou, X.-L.; Dai, L.-X.; Yu, Y.-H.; Xia,
W.; Sun, J . J . Am. Chem. Soc. 2001, 123, 6508. (s) Hou, D.-R.,
Reibenspies, J . H.; Burgess, K. J . Org. Chem. 2001, 66, 206. (t)
Gilbertson, S. R.; Genov, D. G.; Rheingold, A. L. Org. Lett. 2000, 2,
2885. (u) Manoury, E.; Fossey, J .; A¨ıt-Haddou, H.; Daran, J .-C.;
Balavoine, G. G. A. Organometallics 2000, 19, 3736. (v) Go´mez, M.;
J ansat, S.; Muller, G.; Panyella, D.; van Leeuwen, P. W. N. M.; Kamer,
P. C. J .; Goubitz, K.; Fraanje, J . Organometallics 1999, 18, 4970. (w)
Hou, D.-R.; Burgess, K. Org. Lett. 1999, 1, 1745. (x) Park, J .; Quan,
Z.; Lee, S.; Han Ahn, K.; Cho, C.-W. J . Organomet. Chem. 1999, 584,
140. (y) Lee, S.-g.; Lim, C. W.; Song, C. E.; Kim, K. M.; J um, C. H. J .
Org. Chem. 1999, 64, 4445. (z) Selvakumar, K.; Valentini, M.; Wo¨rle,
M.; Pregosin, P. S.; Albinati, A. Organometallics 1999, 18, 1207.
(9) Some recent examples of Pd-catalyzed AAA reaction using
iminophosphine ligands: (a) Mercier, F.; Brebion, F.; Dupont, R.;
Mathey, F. Tetrahedron: Asymmetry 2003, 14, 3137. (b) Lee, J . H.;
Son, S. U.; Chung, Y. K. Tetrahedron: Asymmetry 2003, 14, 2109. (c)
Hu, X.; Chen, H.; Dai, H.; Hu, X.; Zheng, Z. Tetrahedron: Asymmetry
2003, 14, 2073. (d) Brunner, H.; Scho¨nherr, M.; Zabel, M. Tetrahe-
dron: Asymmetry 2003, 14, 1115. (e) Zablocka, M.; Koprowski, M.;
Donnadieu, B.; Majoral, J .-P.; Achard, M.; Buono, G. Tetrahedron Lett.
2003, 44, 2413. (f) Schenkel, L. B.; Ellman, J . A. Org. Lett. 2003, 5,
545. (g) Hu, X.; Chen, H.; Hu, X.; Dai, H.; Bai, C.; Wang, J .; Zheng, Z.
Tetrahedron Lett. 2002, 43, 9179. (h) Hu, X.; Dai, H.; Hu, X.; Chen,
H.; Wang, J .; Bai, C.; Zheng, Z. Tetrahedron: Asymmetry 2002, 13,
1687. (i) Fukuda, T.; Takehara, A.; Iwao, M. Tetrahedron: Asymmetry
2001, 12, 2793. (j) Malaise´, G.; Barloy, L.; Osborn, J . A. Tetrahedron
Lett. 2001, 42, 7417. (k) Park, H.-J .; Han, J . W.; Seo, H.; J ang, H.-Y.;
Chung, Y. K.; Suh, J . J . Mol. Catal. A 2001, 174, 151. (l) J ang, H.-Y.;
Seo, H.; Han, J . W.; Chung, Y. K. Tetrahedron Lett. 2000, 41, 5083.
(m) Saitoh, A.; Achiwa, K.; Tanaka, K.; Morimoto, T. J . Org. Chem.
2000, 65, 4227. (n) Kohara, T.; Hashimoto, Y.; Saigo, K. Synlett 2000,
517. (o) Kwong, H.-L.; Cheng, L.-S.; Lee, W.-S. J . Mol. Catal. A 1999,
150, 23. (p) Suzuki, Y.; Ogata, Y.; Hiroi, K. Tetrahedron: Asymmetry
1999, 10, 1219. (q) Saitoh, A.; Misawa, M.; Morimoto, T. Synlett 1999,
483.
(10) (a) Mino, T.; Komatsumoto, E.; Nakadai, S.; Toyoda, H.;
Sakamoto, M.; Fujita, T. J . Mol. Catal. A 2003, 196, 13. (b) Mino, T.;
Ogawa, T.; Yamashita, M. J . Organomet. Chem. 2003, 665, 122. (c)
Mino, T.; Ogawa, T.; Yamashita, M. Heterocycles 2001, 55, 453. (d)
Mino, T.; Shiotsuki, M.; Yamamoto, N.; Suenaga, T.; Sakamoto, M.;
Fujita, T.; Yamashita, M. J . Org. Chem. 2001, 66, 1795. (e) Enders,
D.; Peters, R.; Lochtman, R.; Runsink, J . Eur. J . Org. Chem. 2000,
2839. (f) Mino, T.; Imiya, W.; Yamashita, M. Synlett 1997, 583.
(11) Some recent examples of Pd-catalyzed AAA reaction using other
phosphine ligands containing sp2 nitrogen: (a) Uenishi, J .; Hamada,
M. Tetrahedron: Asymmetry 2001, 12, 2999. (b) Chelucci G.; Saba, A.;
Soccolini, F. Tetrahedron 2001, 57, 9989. (c) You S.-L.; Hou, X.-L.; Dai,
L.-X. J . Organomet. Chem. 2001, 637-639, 762. (d) Brnardinelli, G.;
Ku¨ndig, E. P.; Meier, P.; Pfaltz, A.; Radkowski, K.; Zimmermann, N.;
Neuburger-Zehnder, M. Helv. Chim. Acta 2001, 84, 3233. (e) Liu, S.;
Mu¨ller, J . F. K.; Neuburger, M.; Schaffner, S.; Zehnder, M. Helv. Chim.
Acta 2000, 83, 1256. (f) McCarthy, M.; Guiry, P. J . Polyhedron 2000,
19, 541. (g) Ito, K.; Kashiwagi, R.; Iwasaki, K.; Katsuki, T. Synlett 1999,
1563. (h) Han, J . W.; J ang, H.-Y.; Chung, Y. K. Tetrahedron: Asym-
metry 1999, 10, 2853. (i) Lee, S.-G.; Lee, S. H.; Song, C. E.; Chung, B.
Y. Tetrahedron: Asymmetry 1999, 10, 1795.
(12) Some recent examples of Pd-catalyzed AAA reaction using
aminophosphine ligands containing sp3 nitrogen: (a) Nakano, H.;
Yokoyama, J .; Okuyama, Y.; Fujita, R.; Hongo, H. Tetrahedron:
Asymmetry 2003, 14, 2361. (b) Wang, Y.; Li, X.; Sun, J .; Ding, K.
Organometallics 2003, 22, 1856. (c) Lee, E.-K.; Kim, S.-H.; J ung, B.-
H.; Ahn, W.-S.; Kim, G.-J . Tetrahedron Lett. 2003, 44, 1971. (d) J in,
M.-J .; Kim, S.-H.; Lee, S.-J .; Kim, Y.-M. Tetrahedron Lett. 2002, 43,
7409. (e) Dyker, G.; Breitenstein, K.; Henkel, G. Tetrahedron: Asym-
metry 2002, 13, 1929. (f) Kawamura, M.; Kiyotake, R.; Kudo, K.
Chirality 2002, 14, 724. (g) Wang, Y.; Li, X.; Ding, K. Tetrahedron:
Asymmetry 2002, 13, 1291. (h) Xiao, L.; Weissennsteiner, W.; Mereiter,
K.; Widhalm, M. J . Org. Chem. 2002, 67, 2206. (i) Widhalm, M.;
Nettekoven, U.; Kalchhauser, H.; Mereiter, K.; Calhorda, M. J .; Felix,
V. Organometallics 2002, 21, 315. (j) Stranne, R.; Vasse, J .-L.; Moberg,
C. Org. Lett. 2001, 3, 2525. (k) Mino, T.; Hata, S.; Ohtaka, K.;
Sakamoto, M.; Fujita, T. Tetrahedron Lett. 2001, 42, 4837. (l) Anderson,
J . C.; Cubbon, R. J .; Harling, J . D. Tetrahedron: Asymmetry 2001, 12,
923. (m) Uozumi, Y.; Shibatomi, K. J . Am. Chem. Soc. 2001, 123, 2919.
(n) Wang, Y.; Guo, H.; Ding, K. Tetrahedron: Asymmetry 2000, 11,
4153. (o) Kim, Y. K.; Lee, S. J .; Ahn, K. H. J . Org. Chem. 2000, 65,
7807. (p) Robert, F.; Delbecq, F.; Nguefack, C.; Sinou, D. Eur. J . Inorg.
Chem. 2000, 351. (q) Anderson, M. S.; Mirza, A. R.; Tonks, L.; Williams,
J . M. J . Tetrahedron: Asymmetry 1999, 10, 2829. (r) J in, M.-J .; J ung,
J .-A.; Kim, S.-H. Tetrahedron Lett. 1999, 40, 5197. (s) Robert, F.;
Gaillard, N.; Sinou, D. J . Mol. Catal. A 1999, 144, 473. (t) Tanner, D.;
Wyatt, P.; J ohansson, F.; Bertilsson, S. K.; Andersson, P. G. Acta Chem.
Scand. 1999, 53, 263.
6680 J . Org. Chem., Vol. 69, No. 20, 2004

Chiral (S)-Prolinol-Derived Ligands
TABLE 1. P a lla d iu m -Ca ta lyzed AAA Rea ction Usin g
SCHEME 1. Syn th esis of Ch ir a l Am in op h osp h in e
Liga n d s (S)-4
Ch ir a l Liga n d s (R)-3 a n d (S)-4a
yield
%
ee/%c
b
entry
ligand
R1
R2
H
(config)d
1
2
3
4
(S)-4a
(S)-4b
(S)-4c
(S)-4d
(S)-4e
(S)-4e
(S)-4f
(R)-3a
(R)-3b
H
98
86
94
89
91
41
93
97
97
58 (S)
89 (S)
92 (S)
87 (S)
93 (S)
96 (S)
83 (S)
40 (R)
85 (R)
-CHdCH-CHdCH-
Me
Et
OMe
OMe
Ph
H
H
H
H
H
H
H
5
6e
7
8f
9f
H
OMe
a
The reaction was carried out at 0.5 mmol scale in toluene at
rt for 24 h with 3.0 equiv of 8a and BSA, in the presence of LiOAc
(2 mol %), chiral ligand (4 mol %), and [Pd(η3-C3H5)Cl]2 (2 mol
d
%). b Isolated yield. c Determined by chiral HPLC analysis. Estab-
lished from the optical rotation by comparison with the literature
data.17 e The reaction was carried out at -20 °C for 7 days. f See
ref 14.
SCHEME 3. Silyl Eth er ifica tion of (S)-4e by BSA
SCHEME 2. P a lla d iu m -Ca ta lyzed Asym m etr ic
Allylic Alk yla tion (AAA Rea ction )
tuted analogues of (S)-4a , brought about high asymmetric
induction (entries 2-5 and 7). Although enantioselectiv-
ity was improved to 96% ee by decreasing the reaction
temperature (-20 °C), the reaction rate became slow
(entry 6). To our surprise, the ligand (S)-4a gave enan-
tioselectivity higher than that with the ligand (R)-3a
possessing methoxyl group in the terminal of the side
chain (entry 1 vs 8), just as it appeared in the case of a
6′-methoxyl-type ligand such as (S)-4e versus (R)-3b
(entry 5 vs 9). It was noteworthy that the asymmetric
induction was emphasized, although the hydroxyl group
of (R)-3 is sterically less hindered than the methoxyl
group of (S)-4.
We consider this unexpected phenomenon to be caused
by the effect of the 2-pyrrolidinyl substituent; if the
hydroxyl groups in the Pd-ligand complexes could be
easily converted into the silyl ether groups by excess BSA
in situ,18 then the 2-pyrrolidinyl substituent would be
sterically more hindered than the methoxyl groups,
resulting in an increase in the enantioselectivity of 9a .
Syn th esis a n d Ap p lica tion of Ch ir a l Liga n d (S)-
10a to th e P a lla d iu m -Ca ta lyzed AAA Rea ction .
According to our anticipation, we attempted to react of
(S)-4e with BSA. To a solution of (S)-4e, BSA was added
at room temperature (Scheme 3), and the resulting
product was a novel aminophosphine (S)-10a via the
trimethylsilylation. Using (S)-10a as a ligand, we exam-
ined a palladium-catalyzed AAA reaction in the same
manner (Table 2, entry 2). The reaction provided a level
of chemical yield and enantioselectivity similar to that
of entry 1.
P a lla d iu m -Ca ta lyzed Asym m etr ic Allylic Alk yla -
tion . These chiral aminophosphine ligands (S)-4 were
applied to the palladium-catalyzed asymmetric allylic
alkylation (AAA reaction) of 1,3-diphenyl-2-propenyl
acetate (7a ) with a dimethyl malonate (8a ) (Scheme 2).
This reaction was carried out in the presence of 2 mol %
of [Pd(η3-C3H5)Cl]2, 4 mol % of a chiral ligand, and a
mixture of N,O-bis(trimethylsilyl)acetamide (BSA) and
2 mol % of LiOAc in toluene to give the alkylated product
9a ;14b the results are summarized in Table 1.
The reactions occurred successfully, and the alkylated
product 9a was obtained in good yields (entries 1-5 and
7). The ligand (S)-4a gave the product 9a in low enan-
tiopurity (entry 1), whereas ligands (S)-4b-f, 6′-substi-
(13) Some recent examples of Pd-catalyzed AAA reaction using
pyrrolidinyl-containing aminophosphine ligands: (a) Cheng, X.; Hill,
K. K. Tetrahedron: Asymmetry 2003, 14, 2045. (b) Mino, T.; Tanaka,
Y.; Sato, Y.; Saito, A. Sakamoto, M.; Fujita, T. Tetrahedron Lett. 2003,
44, 4677 and 5759. (c) Lam, H.; Cheng, X.; Steed, J . W.; Aldous, D. J .;
Hill, K. K. Tetrahedron Lett. 2002, 43, 5875. (d) Kondo, K.; Kazuta,
K.; Fujita, H.; Sakamoto, Y.; Murakami, Y. Tetrahedron 2002, 58, 5209.
(e) Farrell, A.; Goddard, R.; Guiry, P. J . J . Org. Chem. 2002, 67, 4209.
(f) Wang, Y.; Li, X.; Ding, K. Tetrahedron Lett. 2002, 43, 159. (g) Mino,
T.; Tanaka, Y.; Akita, K.; Anada, K.; Sakamoto, M.; Fujita, T.
Tetrahedron: Asymmetry 2001, 12, 1677. (h) Okuyama, Y.; Nakano,
H.; Hongo, H. Tetrahedron: Asymmetry 2000, 11, 1193. (i) Cahill, J .
P.; Cunneen, D.; Guiry, P. J . Tetrahedron: Asymmetry 1999, 10, 4157.
(j) Hiroi, K.; Suzuki, Y.; Abe, I. Tetrahedron: Asymmetry 1999, 10,
1173. (k) Hiroi, K.; Suzuki, Y.; Abe, I. Chem. Lett. 1999, 149. (l) Suzuki,
Y.; Abe, I.; Hiroi, K. Heterocycles 1999, 50, 89. (m) Hattori, T.; Komuro,
Y.; Hayashizaka, N.; Takahashi, H.; Miyano, S. Enantiomer 1997, 2,
203.
We next examined reaction conditions of the pal-
ladium-catalyzed AAA reaction. Initially, using (S)-10a
(14) (a) Mino, T.; Tanaka, Y.; Sakamoto, M.; Fujita, T. Tetrahe-
dron: Asymmetry 2001, 12, 2435. (b) Mino, T.; Tanaka, Y.; Sakamoto,
M.; Fujita, T. Heterocycles 2000, 53, 1485.
(15) Mino, T.; Tanaka, Y.; Akita, K.; Sakamoto, M.; Fujita, T.
Heterocycles 2003, 60, 9.
(16) Hattori, T.; Sakamoto, J .; Hayashizaka, N.; Miyano, S. Syn-
thesis 1994, 199.
(17) Hayashi, T.; Yamamoto, A.; Hagihara, T.; Ito, Y. Tetrahedron
Lett. 1986, 27, 191.
(18) (a) Galbraith, M. N.; Horn, D. H. S.; Middleton, E. J .; Hackney,
R. J . J . Chem. Soc., Chem. Commun. 1968, 466. (b) Klebe, J . F.;
Finkbeiner, H.; White, D. M. J . Am. Chem. Soc. 1966, 88, 3390.
J . Org. Chem, Vol. 69, No. 20, 2004 6681

Tanaka et al.
TABLE 2. P a lla d iu m -Ca ta lyzed AAA Rea ction Usin g
TABLE 4. P a lla d iu m -Ca ta lyzed AAA Rea ction of
Ch ir a l Liga n d s (S)-4e a n d (S)-10a a
Va r iou s Allylic Ester s w ith Va r iou s Ma lon a tes Usin g
(S)-10a a s a Liga n d a
yield
%
ee/%c
b
entry
ligand
base
(config)d
temp time yield ee/%c
b
entry
Ar
R1 R2 R3 prod. °C
h
%
(config)
1
2
(S)-4e
(S)-10a
BSA-LiOAc
BSA-LiOAc
93
93
93 (S)
93 (S)
1
2
3
4
5
6
7
Ph
Ph
Ac Me
Piv Me
H
H
H
H
H
H
Me
9a
9a
9b
9c
9d
9e
9f
-10
24
24
97 95 (S)d
92 92 (S)d
79 93
rt
a
The reaction was carried out at 0.5 mmol scale in toluene at
rt for 24 h with 3.0 equiv of 8a and BSA, in the presence of LiOAc
(2 mol %), chiral ligand (4 mol %), and [Pd(η3-C3H5)Cl]2 (2 mol
4-Cl-Ph Ac Me
-30 120
-10
0
Ph
Ph
Ph
Ph
Ac Et
Ac t-Bu
Ac Bn
Ac Et
48
72
72
48
95 97 (S)e
95 80 (S)f
90 95
d
%). b Isolated yield. c Determined by chiral HPLC analysis. Estab-
-20
lished from the optical rotation by comparison with the literature
0
98 98 (R)g
data.17
a
The reaction was carried out at 0.5 mmol scale in toluene with
3.0 equiv of 8 and BSA, in the presence of LiOAc (2 mol %), (S)-
TABLE 3. In flu en ce of Solven t on P a lla d iu m -Ca ta lyzed
b
10a (4 mol %), and [Pd(η3-C3H5)Cl]2 (2 mol %). Isolated yield.
AAA Rea ction Usin g Ch ir a l Liga n d (S)-10a a
d
c Determined by chiral HPLC analysis. Established from the
yield
%
ee/%c
optical rotation by comparison with the literature data.17 e Estab-
lished from the optical rotation by comparison with the literature
data.19 f Established from the optical rotation by comparison with
b
entry
solvent
time/h
(config)d
1
2
3
4
5
6
7
8
toluene
THF
2
3
2
2
2
24
24
2
93
98
93
99
93
90
88
98
93 (S)
91 (S)
92 (S)
90 (S)
91 (S)
87 (S)
82 (S)
89 (S)
g
the literature data.20 Established from the optical rotation by
comparison with the literature data.14a
Et2O
CPMEe
n-hexane
MeCN
DMF
SCHEME 5. Syn th esis of Ch ir a l Am in op h osp h in e
Liga n d s (S)-10
Ph-CF3
a
The reaction was carried out at 0.5 mmol scale at rt with 3.0
equiv of 8a and BSA, in the presence of LiOAc (2 mol %), (S)-10a
b
(4 mol %), and [Pd(η3-C3H5)Cl]2 (2 mol %). Isolated yield. c De-
d
termined by chiral HPLC analysis. Established from the optical
rotation by comparison with the literature data.17 e Cyclopentyl
methyl ether.
SCHEME 4. P a lla d iu m -Ca ta lyzed AAA Rea ction of
Va r iou s Allylic Ester s w ith Va r iou s Ma lon a tes
Usin g (S)-10a a s a Liga n d
converted to 9a with high enantioselectivity (entry 2).
The reaction using 4, 4′-dichloro-substituted allylic ester
7c as a substrate provided the corresponding product 9b
at the same level of enantioselectivity as entry 2;
however, the reaction rate became slow as a result of the
temperature decreasing (entry 3). The enantioselectivity
was improved when diethyl malonate 8b was used as a
sterically more-hindered nucleophile (entry 4), but the
same effect did not occur in the case of di-tert-butyl
malonate 8c and dibenzyl malonate 8d (entries 5 and
6). The enantioselectivity was achieved to 98% ee when
diethylmethyl malonate 8e was used at 0 °C. (entry 7).
Ch ir a l Am in op h osp h in e Liga n d s 10; P r ep a r a tion
a n d Th eir Ca ta lytic Activities. The above results
prompted us to search for sterically more-hindered
ligands. Accordingly, we have designed a series of sily-
lated chiral aminophosphine ligands 10 readily prepared
from (S)-4e with the corresponding silyl chlorides (Scheme
5) and applied them to the palladium-catalyzed AAA
reaction in the same manner as described above (Scheme
2). The results are summarized in Table 5.
The reactions were successfully carried out with high
enantioselectivities at room temperature, except for when
(S)-10c was used as a ligand (entry 3). In particular,
using chiral ligand (S)-10b slightly increased the enan-
tioselectivity (entry 2). To improve the enantioselectivity,
we further examined the effect of decreasing the tem-
perature. At -20 °C, enantioselectivity was achieved to
98% ee in Et2O (entry 6), although its reaction rate
became slow compared to the reaction carried out in
toluene at the same temperature (entry 5).
as a ligand, we conducted this reaction in various
solvents, and the results are summarized in Table 3.
In the case of toluene, the reaction was almost finished
within 2 h (entry 1). Changing the solvent to various
ethers brought similar levels of chemical yields and
enantioselectivities in comparison with entry 1 (entry
2-4). Using a low-polar solvent, such as n-hexane, also
provided a similar level of catalytic activity (entry 5).
However, use of non-ether-type polar solvents decreased
not only the reactivities but also the enantioselectivities
(entries 6 and 7). When R,R,R-trifluorotoluene was used
as a solvent, high reactivity was observed, though the
enantioselectivity was slightly lower (entry 8).
In addition, we examined AAA reactions of various
dialkyl malonates and allyl esters using (S)-10a as a
ligand (Scheme 4). As shown in Table 4, the reaction at
-10 °C provided high enantiomeric excess compared to
the case in which the reaction took place at room
temperature (entry 1). Pivaroyl allylic ester 7b was also
St r u ct u r a l E lu cid a t ion of Ch ir a l Am in op h os-
p h in e Liga n d s a n d Th eir P a lla d iu m Com p lexes. On
6682 J . Org. Chem., Vol. 69, No. 20, 2004

Chiral (S)-Prolinol-Derived Ligands
TABLE 5. P a lla d iu m -Ca ta lyzed AAA Rea ction s Usin g
SCHEME 7. P r ep a r a tion of P a lla d iu m Com p lexes
w ith Ch ir a l Liga n d s (S)-4e a n d (S)-10a
Ch ir a l Liga n d s (S)-10a
yield
%
ee/%c
b
entry
ligand
solvent
temp/°C
(config)d
1
2
3
4
5
6
(S)-10a
(S)-10b
(S)-10c
(S)-10d
(S)-10b
(S)-10b
toluene
toluene
toluene
toluene
toluene
Et2O
rt
rt
rt
rt
-20
-20
93
90
98
90
69
46
93 (S)
94 (S)
78 (S)
91 (S)
97 (S)
98 (S)
a
TABLE 6. P a lla d iu m -Ca ta lyzed AAA Rea ction s Usin g
The reaction was carried out at 0.5 mmol scale for 24 h with
Ch ir a l Liga n d s (S)-4e a n d (S)-10a a
3.0 equiv of 8a and BSA, in the presence of LiOAc (2 mol %), chiral
ligand (4 mol %), and [Pd(η3-C3H5)Cl]2 (2 mol %). Isolated yield.
b
yield
%
ee/%c
c Determined by chiral HPLC analysis. Established from the
d
b
entry
ligand
base
(config)d
optical rotation by comparison with the literature data.17
1
2
(S)-4e
(S)-10a
NaH
NaH
68
79
68 (S)
79 (S)
SCHEME 6. C(a r yl)-N(a m in e) Bon d Rota tion of
(S)-4e a n d (S)-10a
a
The reaction was carried out at 0.5 mmol scale in toluene at
rt for 24 h with 3.0 equiv of 8a and NaH, in the presence of chiral
b
ligand (4 mol %) and [Pd(η3-C3H5)Cl]2 (2 mol %). Isolated yield.
d
c Determined by chiral HPLC analysis. Established from the
optical rotation by comparison with the literature data.17
indicating that the more stable structures feature the aS-
type configuration of their C(aryl)-N(amine) axis.22
These configurations clearly suggest that both of the
2-pyrrolidinyl side chains approach the diphenyl phos-
phinyl groups.
the basis of these results, we investigated the 2-pyrro-
lidinyl sidechain of (S)-4 and (S)-10 further from the
viewpoint of structural studies. Recently, we discovered
the C(aryl)-N(amine) bond atropisomeric aminophos-
phines and applied them to the palladium-catalyzed AAA
reaction.21 The results demonstrated that the high asym-
metric induction was urged to the C(aryl)-N(amine) axial
chirality. Those results indicate that there are two types
of candidates in the configuration of (S)-4 and (S)-10, and
they are of the (aR)- or (aS)-configuration on their
C(aryl)-N(amine) axis (Scheme 6). However, neither of
the diastereomers derived from C(aryl)-N(amine) axial
chirality and 2-pyrrolidinyl chirality were observed from
the result of TLC nor by determining the NMR at various
temperatures in toluene-d. Thus, despite the fact that
these observations suggest the C(aryl)-N(amine) axis in
(S)-4 and (S)-10 is configurationally flexible, the high
asymmetric induction was urged to the ligands (S)-4 and
(S)-10. We considered that the 2-pyrrolidinyl side chains
of (S)-4 and (S)-10 would be distant from the aryl moiety
containing methoxyl and phosphino groups as a result
of their steric stability; therefore, the (aS)-configuration
is more favorable than the (aR)-configuration on their
C(aryl)-N(amine) axis when the ligand coordinates with
the palladium atom. Furthermore, it appears that the
2-pyrrolidinyl chirality induces the C(aryl)-N(amine)
axial chirality in the molecule. To confirm our anticipa-
tion, we examined the single-crystal X-ray diffraction
analysis of (S)-4e and (S)-10a .
Treating the corresponding chiral ligand with Pd-
(MeCN)2Cl2 in chloroform, we next prepared the pal-
ladium complexes 11a and 11b (Scheme 7). Although the
attempt at X-ray analysis of the palladium complex 11b
was unsuccessful, we were eventually able to obtain
X-ray diffraction patterns by exchanging the complex 11b
to 11a . As a result, the ligand (S)-4e is P,N-coordinated
with a palladium atom by (aS)-configuration, and the
2-pyrrolidinyl side chain expectantly approaches the
central palladium atom (Figure S3, Supporting Informa-
tion).22 The unit cells of (S)-4e, (S)-10a , and 11a contain
two independent molecules, but another molecule also
shows the aS-type configuration of its C(aryl)-N(amine)
axis. These results clearly suggest that the (aS)-config-
uration is more favorable than the (aR)-configuration on
the C(aryl)-N(amine) axis when the ligand coordinates
to the palladium atom, as if the 2-pyrrolidinyl chirality
disturbs the N-inversion in molecules.
In addition, we prepared the chloroform-d solution of
complex 11a and gradually analyzed 1H NMR spectra
involving addition of BSA in portions. Following that, we
compared these spectra to the spectrum of the complex
11b (Figure S4, Supporting Information).22 The spectrum
of the complex 11a was gradually approximated to that
of the complex 11b each time BSA was added.
Moreover, we examined the palladium-catalyzed AAA
reaction under the condition that trimethylsilylation of
(S)-4e does not occur in situ, such as when using NaH
instead of BSA-LiOAc, and found that the enantioselec-
tivity of 9a was higher than that in the case of (S)-4e
(Table 6). This result indicate that the hydroxyl group
of the (S)-4-palladium complexes was trimethylsilylated
by excess BSA in the AAA reaction system; that the
resulting trimethylsiloxyl group was sterically more
hindered than the methoxyl group emphasized the enan-
tioselectivity of the alkylated product.
The structures of the chiral ligands, both (S)-4e and
(S)-10a containing a 2-pyrrolidinyl moiety, were deter-
mined by single-crystal X-ray diffraction analysis, with
the results (Figures S1 and S2, Supporting Information)
(19) Vyskocil, S.; Smrcina, M.; Hanus, V.; Polasek, M.; Kocovsky,
P. J . Org. Chem. 1998, 63, 7738.
(20) Seebach, D.; Devaquet, E.; Ernst, A.; Hayakawa, M.; Kuehnle,
F. N. M.; Schweizer, W. B.; Weber, B. Helv. Chim. Acta 1995, 78, 1636.
(21) Mino, T.; Tanaka, Y.; Yabusaki, T.; Okumura, D.; Sakamoto,
M.; Fujita, T. Tetrahedron: Asymmetry 2003, 14, 2503.
(22) See Supporting Information.
J . Org. Chem, Vol. 69, No. 20, 2004 6683

Tanaka et al.
SCHEME 8. P la u sible Asym m etr ic In d u ction
P r ocess of P a lla d iu m -Ca ta lyzed AAA Rea ction
Usin g Ch ir a l Liga n d s (S)-4e a n d (S)-10a
containing aminophosphine ligands are more favorable
than the (aR)-configuration on their C(aryl)-N(amine)
axis, and the hydroxyl group of the palladium complex
formed by (S)-4e was trimethylsilylated by excess BSA
in situ. We are currently investigating other asymmetric
reactions further using aminophosphines such as (S)-4e
and (S)-10 as the chiral ligands or chiral base catalysts.
Exp er im en ta l Section
P r ep a r a tion of P h osp h in e Oxid es 5. Diphenyl(2-meth-
oxyphenyl)phosphine oxide 5a is commercially available.
1-Methoxy-2-diphenylphosphinonaphthalene oxide 5b ,13g,16
2-methoxy-3-methylphenyldiphenylphosphine oxide 5c,14a 2,3-
dimethoxyphenyldiphenylphosphine oxide 5e,14a and 2-meth-
oxy-3-phenylphenyldiphenylphosphine oxide 5f14a were pre-
pared according to the literature method.
2-Met h oxy-3-et h ylp h en yld ip h en ylp h osp h in e Oxid e
(5d ). To mixture of 2-ethylanisole (10.0 mmol), TMEDA (1.51
mL, 10.0 mmol), and ether (25 mL) was added dropwise n-BuLi
in hexane (9.2 mL, 14.7 mmol, 1.66 M) over 10 min. The
mixture was stirred at room temperature for 2 h and then
treated with chlorodiphenylphosphine (1.8 mL, 10.0 mmol),
and the resulting mixture was diluted with ether and quenched
with 2 M aqueous HCl. The organic layer was washed with 2
M aqueous Na2CO3 and brine, dried over MgSO4, and concen-
trated under reduced pressure. The residue was dissolved in
AcOH (50 mL), treated with 30% aqueous H2O2 (1.5 mL), and
then gradually heated to 80 °C for 2 h. The mixture was cooled
to room temperature, diluted with ether (100 mL), and then
treated with 2 M aqueous NaOH at 0 °C. The water layer was
extracted with ether, and the combined extracts were washed
with water, dried over MgSO4, and concentrated under reduced
pressure. The residue was purified by silica gel chromatogra-
phy (elution with n-hexane/EtOAc ) 1/3): 33%; mp 108-111
Finally, we suggested the plausible asymmetric induc-
tion process of the palladium-catalyzed AAA reaction of
7a with 8a using chiral ligands (S)-4e and (S)-10a in
Scheme 8. There are two candidates, A and B, which are
considerable reaction intermediates formed from chiral
ligands (S)-4e and (S)-10a . However, B has been proved
unstable as a result of steric hindrance of the phenyl
rings between the allylic substrate and the ligand. In
addition, the nucleophilic attack of 8a is hypothesized
to be difficult because of steric hindrance of the bulky
2-pyrrolidinyl trimethylsiloxymethyl group. Therefore,
the reaction probably proceeds through a W-type inter-
mediate A rather than an M-type intermediate B. The
nucleophilic attack occurs predominantly at the allyl
terminus from the trans to the better π-acceptor (P >
N).23 As a result, the (S)-product 9a was obtained in this
reaction using the chiral aminophosphines (S)-4 and (S)-
10 as ligands.
1
°C; H NMR (300 Mz, CDCl3) δ 1.24 (t, J ) 7.6 Hz, 3H), 2.68
(q, J ) 7.6 Hz, 2H), 3.47 (s, 3H), 7.05-7.13 (m, 1H), 7.15-
7.24 (m, 1H), 7.40-7.56 (m, 7H), 7.67-7.77 (m, 4H); 13C NMR
(75 Mz, CDCl3) δ 14.5, 22.39, 62.0, 123.9 (d, J cp ) 12.9 Hz),
125.8, 127.2, 128.2, 128.4, 131.5 (d, J cp ) 2.8 Hz), 131.6, 131.8,
132.1 (d, J cp ) 9.2 Hz), 132.8, 134.2, 134.6 (d, J cp ) 2.1 Hz),
137.9 (d, J cp ) 6.2 Hz), 160.8 (d, J cp ) 2.8 Hz); 31P NMR (121
Mz, CDCl3) δ 28.0; EI-MS m/z (rel intensity) 336 (M+, 98);
HRMS (FAB-MS) m/z calcd for C21H21O2P + H 337.1357, found
337.1355.
Typ ica l P r oced u r e for P r ep a r a tion of Am in op h os-
p h in e Oxid es 6. To the solution of (S)-prolinol (1.03 mmol)
in THF (1 mL) was added slowly n-BuLi in hexane (1.4 mL,
2.2 mmol, 1.56 M) at -80 °C for 10 min and then room
temperature for 2 h under an argon atmosphere. After phos-
phine oxide 5 (1.0 mmol) was added at 0 °C, stirring was
continued for 20 h at room temperature. The mixture was
diluted with ether and quenched with saturated aqueous NH4-
Cl. The organic layer was washed with brine, dried over
MgSO4, and concentrated under reduced pressure. The residue
was purified by silica gel chromatography. (S)-1-[2′-(Diphen-
ylphosphinyl)-1′-naphthalenyl]-2-(hydroxymethyl)pyrroli-
dine 6b was prepared according to the literature method.13g
Con clu sion
In summary, we were able to achieve highly enantio-
selective palladium-catalyzed asymmetric allylic alkyla-
tion using a novel chiral pyrrolidinyl-containing amino-
phosphine ligands (S)-4 possessing a hydroxyl group.
Furthermore, the trialkylsilylated aminophosphine ligand
(S)-10 also produced good results in the palladium-
catalyzed asymmetric allylic alkylation. Moreover, by
employing various structural methods, we were able to
reveal that the (aS)-configuration of chiral pyrrolidinyl-
(S)-1-[2′-(Diph en ylph osph in yl)ph en yl]-2-(h ydr oxym eth -
yl)p yr r olid in e (6a ): 64%; mp 179-181 °C; [R]25D -112 (c 1.00,
CHCl3); 1H NMR (300 Mz, CDCl3) δ 1.14-1.31 (m, 1H), 1.43-
1.57 (m, 1H), 1.71-1.85 (m, 1H), 1.85-2.06 (m, 2H), 2.29-
2.42 (m, 1H), 3.25-3.39 (m, 2H), 3.56 (d, J ) 10.8 Hz, 1H),
6.36 (br-s, 1H), 6.98-7.17 (m, 2H), 7.38-7.59 (m, 8H), 7.67-
7.85 (m, 4H); 13C NMR (75 Mz, CDCl3) δ 24.8, 26.3, 58.1, 61.5,
69.1, 125.5, 125.7, 127.2, 127.3, 128.6, 128.8 (d, J cp ) 4.4 Hz),
128.9, 131.5, 131.7, 132.1, 132.6, 132.7, 133.3, 134.4, 134.6,
157.5; 31P NMR (121 Mz, CDCl3) δ 28.8; EI-MS m/z (rel
intensity) 377 (M+, 1); HRMS (FAB-MS) m/z calcd for C23H24
NO2P + H 378.1623, found 378.1602.
-
(23) Åkermark, B.; Hansson, S.; Krakenberger, B.; Vitagliano, A.;
Zetterberg, K. Organometallics 1984, 3, 679.
6684 J . Org. Chem., Vol. 69, No. 20, 2004

Chiral (S)-Prolinol-Derived Ligands
(S)-1-[2′-(Dip h en ylp h osp h in yl)-6′-m eth ylp h en yl]-2-(h y-
was purified by silica gel chromatography (elution with n-
hexane/EtOAc ) 6/1). (S)-1-[2′-(Diphenylphosphino)-1′-naph-
thalenyl]-2-(hydroxymethyl)pyrrolidine 4b was prepared ac-
cording to the literature method.13g
d r oxym eth yl)p yr r olid in e (6c): 76%; mp 163-166 °C; [R]25
D
1
-81.5 (c 0.27, CHCl3); H NMR (300 Mz, CDCl3) δ 1.37-1.49
(m, 1H), 1.49-1.68 (m, 2H), 1.80-2.04 (m, 2H), 2.30 (s, 3H),
2.61 (dd, J ) 8.4 and 15.5 Hz, 1H), 3.38 (ddd, J ) 5.5, 8.8 and
14.3 Hz, 1H), 3.45-3.56 (m, 1H), 3.56-3.66 (m, 1H), 6.72-
6.81 (m, 1H), 6.89 (ddd, J ) 1.3, 7.7 and 14.5 Hz, 1H), 7.06
(dt, J ) 3.2 and 7.6 Hz, 1H), 7.37 (d, J ) 7.5 Hz, 1H), 7.40-
7.56 (m, 6H), 7.61-7.72 (m, 2H), 7.72-7.82 (m, 2H); 13C NMR
(75 Mz, CDCl3) δ 19.8, 26.0, 28.1, 53.9, 63.5, 65.9, 125.8 (d,
J cp ) 14.7 Hz), 128.7 (d, J cp ) 5.1 Hz), 128.8 (d, J cp ) 4.4 Hz),
131.6, 131.8, 132.8 (d J cp ) 8.8 Hz), 133.2 (d, J cp ) 13.6 Hz),
134.2, 134.6, 135.1, 136.5, 138.1 (d, J cp ) 2.0 Hz), 139.8 (d,
J cp ) 7.9 Hz); 31P NMR (121 Mz, CDCl3) δ 30.1; FAB-MS m/z
(rel intensity) 392 (M+ + 1, 100); HRMS (FAB-MS) m/z calcd
for C24H26NO2P + H 392.1779, found 392.1777.
(S)-1-[2′-(Diph en ylph osph in o)ph en yl]-2-(h ydr oxym eth -
yl)p yr r olid in e (4a ): 90%; mp 69-70 °C; [R]25 +0.3 (c 0.31,
D
CHCl3); 1H NMR (300 Mz, CDCl3) δ 1.50-1.76 (m, 2H), 1.84-
2.07 (m, 2H), 2.38-2.53 (m, 1H), 2.53-2.68 (m, 1H), 3.25-
3.47 (m, 2H), 3.47-3.66 (m, 2H), 6.86 (ddd, J ) 1.5, 3.8 and
7.7 Hz, 1H), 7.09 (dt, J ) 0.7 and 7.6 Hz, 1H), 7.21-7.31 (m,
3H), 7.31-7.41 (m, 9H); 13C NMR (75 Mz, CDCl3) δ 24.6, 26.9,
56.9, 61.7, 66.1, 124.2 (d, J cp ) 2.2 Hz), 125.8, 128.4, 128.5,
128.5, 128.5, 128.6, 129.0, 130.4, 133.3, 133.7, 133.9, 134.3,
134.6, 136.4 (d, J cp ) 5.6 Hz), 137.1 (d, J cp ) 9.2 Hz), 138.3,
154.0 (d, J cp ) 20.1 Hz); 31P NMR (121 Mz, CDCl3) δ -16.9;
EI-MS m/z (rel intensity) 361 (M+, 7.5); HRMS (FAB-MS) m/z
calcd for C23H24NOP + H 362.1674, found 362.1659.
(S)-1-[2′-(Dip h en ylp h osp h in yl)-6′-et h ylp h en yl]-2-(h y-
d r oxym eth yl)p yr r olid in e (6d ): 36%; mp 142-144 °C; [R]25
D
(S)-1-[2′-(Dip h en ylp h osp h in o)-6′-m eth ylp h en yl]-2-(h y-
-85.0 (c 1.01, CHCl3); 1H NMR (300 Mz, CDCl3) δ 1.24 (t, J )
7.5 Hz, 3H), 1.35-1.47 (m, 1H), 1.47-1.61 (m, 1H), 1.61-1.70
(m, 1H), 1.85-2.06 (m, 2H), 2.50-2.70 (m, 3H), 3.30-3.41 (m,
1H), 3.41-3.49 (m, 1H), 3.59-3.68 (m, 1H), 6.78 (ddd, J ) 1.7,
5.0 and 9.3 Hz, 1H), 6.89 (ddd, J ) 1.5, 7.6 and 14.7 Hz, 1H),
7.12 (dt, J ) 3.1 and 7.7 Hz, 1H), 7.40-7.55 (m, 7H), 7.62-
7.73 (m, 2H), 7.73-7.82 (m, 2H); 13C NMR (75 Mz, CDCl3) δ
15.2, 24.0, 25.5, 27.6, 54.7, 62.9, 67.1, 125.7 (d, J cp ) 14.6 Hz),
128.3 (d, J cp ) 6.0 Hz), 128.4 (d, J cp ) 5.13 Hz) 131.2, 131.4,
132.3 (d, J cp ) 8.7 Hz), 132.5, 132.7 (d, J cp ) 13.4 Hz), 134.0
(d, J cp ) 21.1 Hz), 134.8, 135.9, 136.2, 145.9 (d, J cp ) 7.7 Hz),
151.9; 31P NMR (121 Mz, CDCl3) δ 30.0; FAB-MS m/z (rel
intensity) 406 (M+ + 1, 99); HRMS (FAB-MS) m/z calcd for
d r oxym eth yl)p yr r olid in e (4c): 91%; mp 76-79 °C; [R]25
D
1
+83.7 (c 1.04, CHCl3); H NMR (300 Mz, CDCl3) δ 1.60-1.80
(m, 2H), 1.90-2.18 (m, 3H), 2.28 (s, 3H), 2.81 (dd, J ) 7.8 and
16.0 Hz, 1H), 3.41 (dt, J ) 1.5 and 11.7 Hz, 1H), 3.53 (dt, J )
1.1 and 6.0 Hz, 1H), 3.72 (d, J ) 12.0 Hz, 1H), 4.50 (dt, J )
3.2 and 12.4 Hz, 1H), 6.71 (ddd, J ) 1.1, 3.0 and 6.9 Hz 1H),
7.06 (t, J ) 7.5 Hz, 1H), 7.14-7.24 (m, 3H), 7.27-7.38 (m, 8H);
13C NMR (75 Mz, CDCl3) δ 19.2, 25.9, 28.5, 53.3, 63.2, 64.1,
126.9, 128.8, 128.8 (d, J cp ) 6.3 Hz), 128.9 (d, J cp ) 8.0 Hz),
129.6, 131.7, 134.1 (d, J cp ) 18.8 Hz), 134.9 (d, J cp ) 20.6 Hz),
136.6 (d, J cp ) 3.7 Hz), 137.9, 138.2 (d, J cp ) 8.2 Hz), 141.7 (d,
J cp ) 6.6 Hz), 149.7 (d, J cp ) 20.7 Hz); 31P NMR (121 Mz,
CDCl3) δ -17.2; FAB-MS m/z (rel intensity) 376 (M+ + 1, 98);
HRMS (FAB-MS) m/z calcd for C24H26NOP + H 376.1830,
found 376.1821.
C
25H28NO2P + H 406.1936, found 406.1915.
(S)-1-[2′-(Dip h en ylp h osp h in yl)-6′-m et h oxyp h en yl]-2-
(h yd r oxym et h yl)p yr r olid in e (6e): 93%; mp 171-172 °C;
[R]25D -111.8 (c 1.04, CHCl3); 1H NMR (300 Mz, CDCl3) δ 1.18-
1.38 (m, 1H), 1.38-1.68 (m, 2H), 1.68-1.90 (m, 2H), 2.5-2.70
(m, 1H), 3.26-3.46 (m, 1H), 3.46-3.70 (m, 2H), 3.82 (s, 3H),
6.52-6.70 (m, 2H), 7.05-7.17 (m, 2H), 7.40-7.56 (m, 6H),
7.62-7.73 (m, 2H), 7.73-7.84 (m, 2H); 13C NMR (75 Mz,
CDCl3) δ 25.4, 27.4, 53.3, 55.1, 63.0, 65.3, 116.7 (d, J cp ) 2.3
Hz), 125.8 (d, J cp ) 12.7 Hz), 126.4 (d, J cp ) 15.9 Hz), 128.2
(d, J cp ) 9.2 Hz), 128.3 (d, J cp ) 8.3 Hz) 131.1, 131.1, 131.2,
131.4 (d, J cp ) 2.6 Hz), 132.0, 132.3 (d, J cp ) 8.8 Hz), 132.7,
133.4, 134.2, 135.3, 136.7, 143.4 (d, J cp ) 3.0 Hz), 159.1 (d,
J cp ) 11.5 Hz); 31P NMR (121 Mz, CDCl3) δ 30.0; FAB-MS m/z
(rel intensity) 408 (M+ + 1, 100); HRMS (FAB-MS) m/z calcd
for C24H26NO3P + H 408.1729, found 408.1728.
(S)-1-[2′-(Dip h en ylp h osp h in o)-6′-et h ylp h en yl]-2-(h y-
d r oxym eth yl)p yr r olid in e (4d ): 78%; mp 82-85 °C; [R]25
D
+72.6 (c 1.06, CHCl3); 1H NMR (300 Mz, CDCl3) δ 1.24 (t, J )
7.5 Hz, 3H), 1.55-1.75 (m, 2H), 1.90-2.20 (m, 1H), 2.59 (q,
J ) 7.4 Hz, 2H), 2.77 (dd, J ) 8.0 and 16.0 Hz, 1H), 3.30-
3.53 (m, 2H), 3.75 (d, J ) 12.0 Hz, 1H), 4.53 (t, J ) 10.7 Hz,
1H), 6.71 (ddd, J ) 1.4, 3.7 and 7.4 Hz, 1H), 7.12 (t, J ) 7.6
Hz, 1H), 7.16-7.24 (m, 2H), 7.28-7.39 (m, 9H); 13C NMR (75
Mz, CDCl3) δ 15.2, 23.6, 25.4, 28.0, 54.1, 62.7, 65.1, 126.7,
128.4, 128.4, 128.5, 129.1, 131.1, 131.7, 133.7 (d, J cp ) 19.0
Hz), 134.5 (d, J cp ) 20.6 Hz), 136.1 (d, J cp ) 3.8 Hz), 137.9 (d,
J cp ) 8.2 Hz), 141.3 (d, J cp ) 7.2 Hz), 144.0, 148.7 (d, J cp
)
20.3 Hz); 31P NMR (121 Mz, CDCl3) δ -17.0; EI-MS m/z (rel
intensity) 389 (M+, 9); HRMS (FAB-MS) m/z calcd for C25H28
NOP + H 390.1987, found 390.1964.
-
(S)-1-[2′-(Dip h en ylp h osp h in yl)-6′-p h en ylp h en yl]-2-(h y-
d r oxym eth yl)p yr r olid in e (6f): 63%; mp 175-177 °C; [R]25
(S)-1-[2′-(Dip h en ylp h osp h in o)-6′-m et h oxyp h en yl]-2-
(h yd r oxym et h yl)p yr r olid in e (4e): 83%; mp 119-120 °C;
[R]25D +68.1 (c 1.04, CHCl3); 1H NMR (300 Mz, CDCl3) δ 1.47-
1.76 (m, 2H), 1.85-2.03 (m, 3H), 2.80 (dd, J ) 7.6 and 15.6
Hz, 1H), 3.39 (t, J ) 10.5 Hz, 1H), 3.55-3.70 (m, 2H), 3.81 (s,
3H), 4.26 (t, J ) 11.4 Hz, 1H), 6.38-6.45 (m, 1H), 6.91 (d, J )
8.1 Hz, 1H), 7.10 (t, J ) 7.9 Hz, 1H), 7.18-7.28 (m, 2H), 7.28-
7.40 (m, 8H); 13C NMR (75 Mz, CDCl3) δ 25.3, 27.8, 52.8, 55.0,
62.9, 63.7, 112.8, 124.6, 127.1 (d, J cp ) 2.1 Hz), 128.4, 128.4
(d, J cp ) 6.6 Hz,), 128.4 (d, J cp ) 5.1 Hz,), 133.8 (d, J cp ) 19.2
Hz,), 134.5 (d, J cp ) 20.9 Hz,), 136.3 (d, J cp ) 3.8 Hz), 137.6
(d, J cp ) 9.1 Hz), 140.3 (d, J cp ) 20.6 Hz), 141.9 (d, J cp ) 4.1
Hz), 158.2 (d, J cp ) 3.8 Hz); 31P NMR (121 Mz, CDCl3) δ -17.2;
FAB-MS m/z (rel intensity) 392 (M+ + 1, 77); HRMS (FAB-
MS) m/z calcd for C24H26NO2P + H 392.1779, found 392.1777.
D
1
+4.4 (c 0.79, CHCl3); H NMR (300 Mz, CDCl3) δ 1.09-1.26
(m, 2H), 1.26-1.50 (m, 1H), 1.62-1.80 (m, 1H), 2.52-2.72 (m,
2H), 2.98 (br-s, 1H), 3.06-3.22 (m, 1H), 3.48 (d, J ) 12.0 Hz,
1H), 6.33 (d, J ) 8.7 Hz, 1H), 6.97-7.13 (m, 2H), 7.18-7.26
(m, 2H), 7.26-7.41 (m, 5H), 7.41-7.61 (m, 5H), 7.61-7.73 (m,
2H), 7.73-7.85 (m, 2H); 13C NMR (75 Mz, CDCl3) δ 25.3, 27.0,
56.2, 63.2, 64.5, 124.0 (d, J cp ) 14.4 Hz), 127.8, 128.6, 128.8,
128.9, 129.6, 132.0 (d, J cp ) 9.8 Hz), 132.1 (d, J cp ) 10.6 Hz),
132.2, 132.6 (d, J cp ) 9.2 Hz), 132.8, 133.5, 133.8, 134.2, 135.2
(d, J cp ) 13.1 Hz), 137.6 (d, J cp ) 2.4 Hz), 141.7, 144.4 (d,
J cp ) 8.1 Hz), 151.6 (d, J cp ) 4.3 Hz); 31P NMR (121 Mz, CDCl3)
δ 32.3; FAB-MS m/z (rel intensity) 454 (M+ + 1, 100); HRMS
(FAB-MS) m/z calcd for C27H26NO2P + H 454.1936, found
454.1943.
Typ ica l P r oced u r e for P r ep a r a tion of Am in op h os-
p h in e Liga n d s 4. To a mixture of phosphine oxide 6 (0.3
mmol) and triethylamine (0.17 mL, 1.2 mmol) in m-xylene (2
mL) was added trichlorosilane (0.12 mL, 1.2 mmol) at 0 °C
under an argon atmosphere. The reaction mixture was refluxed
for 6 h. After being cooled to room temperature, the mixture
was diluted with ether and quenched with 2 M aqueous NaOH
solution. The organic layer was washed with brine, dried over
MgSO4, and concentrated under reduced pressure. The residue
(S)-1-[2′-(Dip h en ylp h osp h in o)-6′-p h en ylp h en yl]-2-(h y-
d r oxym eth yl)p yr r olid in e (4f): 71%; mp 65-68 °C; [R]25
D
1
+90.9 (c 1.11, CHCl3); H NMR (300 Mz, CDCl3) δ 1.19-1.51
(m, 1H), 1.51-1.70 (m, 2H), 1.70-1.85 (m, 1H), 2.70-3.08 (m,
3H), 3.16 (t, J ) 11.3 Hz, 1H), 3.43 (d, J ) 11.6 Hz, 1H), 3.96
(br-s, 1H), 6.95 (ddd, J ) 1.8, 3.8 and 7.2 Hz, 1H), 7.14 (t, J )
7.5 Hz, 1H), 7.17-7.50 (m, 16H); 13C NMR (75 Mz, CDCl3) δ
24.9, 27.6, 56.7, 56.8, 63.1, 125.5, 127.2, 128.1, 128.4, 128.5,
128.6, 129.0, 129.3, 133.6 (d, J cp ) 4.5 Hz), 133.9, 134.1, 134.3,
J . Org. Chem, Vol. 69, No. 20, 2004 6685

Tanaka et al.
136.2 (d, J cp ) 5.9 Hz), 138.2 (d, J cp ) 8.3 Hz), 140.2, 141.4 (d,
J cp ) 1.9 Hz), 142.9, 149.5 (d, J cp ) 22.7 Hz); 31P NMR (121
Mz, CDCl3) δ -17.7; FAB-MS m/z (rel intensity) 438 (M+ + 1,
85); HRMS (FAB-MS) m/z calcd for C29H28NOP + H 438.1987,
found 438.1980.
(S)-1-[2′-(Dip h en ylp h osp h in o)-6′-m et h oxyp h en yl]-2-
(tr im eth ylsila n oxym eth yl)p yr r olid in e (10a ). To a solution
of (S)-1-[2′-(diphenylphosphino)-6′-methoxyphenyl]-2-(hydroxy-
methyl)pyrrolidine 4e (0.20 g, 0.5 mmol) in CHCl3 (1.5 mL)
was added N,O-bis(trimethylsilyl)acetamide (BSA) (0.5 mL, 2.0
mmol) at room temperature. The mixture was stirred for 1 h
under an argon atmosphere and concentrated under reduced
pressure, and the residue was purified by silica gel chroma-
13C NMR (75 Mz, CDCl3) δ 19.2, 24.4, 26.9, 29.6, 52.4, 55.0,
64.1, 67.7, 112.3, 124.8, 126.4, 125.4 (d, J cp ) 3.9 Hz), 128.0
(d, J cp ) 13.6 Hz), 128.0, 128.2 (d, J cp ) 4.4 Hz), 129.2 (d,
J cp ) 3.9 Hz), 133.7, 133.9, 134.2, 134.4 (d, J cp ) 5.8 Hz), 134.5,
135.5 (d, J cp ) 3.6 Hz), 138.7 (d, J cp ) 13.3 Hz), 139.1 (d,
J cp ) 15.4 Hz), 142.3, 157.9; 31P NMR (121 Mz, CDCl3) δ -15.8;
FAB-MS m/z (rel intensity) 630 (M+ + 1, 33); HRMS (FAB-
MS) m/z calcd for C40H44NO2PSi + H 630.2957, found 630.2985.
(S)-1-[2′-(Dip h en ylp h osp h in o)-6′-m et h oxyp h en yl]-2-
[d im eth yl(1′′,1′′,2′′-tr im eth ylp r op yl)sila n oxym eth yl]p yr -
r olid in e (10d ). To a solution of (S)-1-[2′-(diphenylphosphino)-
6′-methoxyphenyl]-2-(hydroxymethyl)pyrrolidine 4e (0.12 g,
0.3 mmol) and triethylamine (0.1 mL, 0.7 mmol) in CDCl3 (2
mL) was added dimethylthexylsilyl chloride (0.12 mL, 0.6
mmol) at room temperature. The mixture was stirred for 21 h
under an argon atmosphere and concentrated under reduced
pressure, and the residue was purified by silica gel chroma-
tography (elution with n-hexane/EtOAc ) 20/1): 95%; mp
1
105-108 °C; [R]25 +51.0 (c 1.02, CHCl3); H NMR (300 Mz,
D
CDCl3) δ -0.08 (s, 9H), 1.55-1.68 (m, 3H), 1.90-2.07 (m, 1H),
2.47 (br-s, 1H), 2.72 (dd, J ) 7.3 and 15.4 Hz, 1H), 3.05 (t,
J ) 10.0 Hz, 1H), 3.29 (dd, J ) 4.0 and 10.0 Hz, 1H), 3.48-
3.60 (m, 1H), 3.73 (s, 3H), 6.31 (ddd, J ) 1.3, 2.8 and 7.6 Hz,
1H), 6.80 (dd, J ) 0.6 and 8.0 Hz, 1H), 6.99 (dt, J ) 0.8 and
7.9 Hz, 1H), 7.12-7.30 (m, 10H); 13C NMR (75 Mz, CDCl3) δ
-0.5, 24.4, 29.7, 52.7, 55.0, 63.8, 66.3 (d, J cp ) 5.0 Hz), 112.3,
124.9, 126.5, 128.2 (d, J cp ) 9.7 Hz), 128.2, 128.3 (d, J cp ) 7.0
Hz), 133.9 (d, J cp ) 20.6 Hz), 134.3 (d, J cp ) 21.1 Hz), 138.7,
138.9, 139.1, 141.2 (d, J cp ) 21.0 Hz), 142.1 (d, J cp ) 4.5 Hz),
157.9 (d, J cp ) 3.6 Hz); 31P NMR (121 Mz, CDCl3) δ -15.7;
EI-MS m/z (rel intensity) 463 (M+, 7.5); HRMS (FAB-MS) m/z
calcd for C27H34NO2PSi + H 464.2175, found 464.2139.
tography (elution with n-hexane/EtOAc ) 8/1): 46%; mp 66-
1
68 °C; [R]25 +41.0 (c 0.10, CHCl3); H NMR (300 Mz, CDCl3)
D
δ -0.05 (d, J ) 9.6 Hz, 6H), 0.76 (d, J ) 1.8 Hz, 6H), 0.83 (d,
J ) 6.9 Hz, 6H), 1.45-1.75 (m, 4H), 1.91-2.08 (m, 1H), 2.50
(br-s, 1H), 2.77 (dd, J ) 8.0 and 15.6 Hz, 1H), 3.18 (t, J ) 9.8
Hz, 1H), 3.41 (dd, J ) 4.2 and 9.9 Hz, 1H), 3.51-3.65 (m, 1H),
3.80 (s, 3H), 6.38 (ddd, J ) 1.3, 2.8 and 7.6 Hz, 1H), 6.87 (d,
J ) 8.1 Hz, 1H), 7.05 (dt, J ) 0.8 and 7.9 Hz, 1H), 7.20-7.35
(m, 10H); 13C NMR (75 Mz, CDCl3) δ -3.4, -3.3, 1.0, 18.5 (d,
J cp ) 1.7 Hz), 20.4 (d, J cp ) 4.9 Hz), 24.4, 25.0, 29.6, 34.1, 52.7,
55.0, 64.0, 66.6 (d, J cp ) 5.5 Hz), 112.4, 124.9, 126.4, 128.1 (d,
J cp ) 10.1 Hz), 128.2, 128.3 (d, J cp ) 6.5 Hz), 133.9 (d, J cp
)
(S)-1-[2′-(Dip h en ylp h osp h in o)-6′-m et h oxyp h en yl]-2-
[d im eth yl(1′′,1′′-d im eth yleth yl)sila n oxym eth yl]p yr r oli-
d in e (10b). To a solution of (S)-1-[2′-(diphenylphosphino)-6′-
methoxyphenyl]-2-(hydroxymethyl)pyrrolidine 4e (0.12 g, 0.3
mmol) and triethylamine (0.1 mL, 0.7 mmol) in CHCl3 (2 mL)
was added the solution of tert-butyldimethylsilyl chloride (0.1
g, 0.66 mmol) in CHCl3 (2 mL) at room temperature. The
mixture was stirred for 18 h under an argon atmosphere and
concentrated under reduced pressure, and the residue was
purified by silica gel chromatography (elution with n-hexane/
20.5 Hz), 134.3 (d, J cp ) 21.3 Hz), 138.9 (d, J cp ) 13.4 Hz),
139.1 (d, J cp ) 15.2 Hz), 141.2, 141.5, 142.3 (d, J cp ) 4.5 Hz),
158.0 (d, J cp ) 3.5 Hz); 31P NMR (121 Mz, CDCl3) δ -15.6;
FAB-MS m/z (rel intensity) 534 (M+ + 1, 32); HRMS (FAB-
MS) m/z calcd for C32H44NO2PSi + H 534.2957, found 534.2933.
P r ep a r a tion of P a lla d iu m Com p lex 11a . To a solution
of Pd(MeCN)2Cl2 (0.013 g, 0.05 mmol) in CHCl3 (0.5 mL) was
added (S)-1-[2′-(diphenylphosphino)-6′-methoxyphenyl]-2-(hy-
droxymethyl)pyrrolidine 4e (0.018 g, 0.05 mmol) at room
temperature, The reaction mixture was stirred for 30 min
under an atmosphere, filtered, and evaporated under reduced
pressure, and purified by recrystallization from EtOH. The
unit cell contains two independent molecules and one solvent
molecule (EtOH): 45%; mp 153-156 °C (dec); [R]25D +223.1 (c
EtOAc ) 15/1): 90%; mp 79-80 °C; [R]25 +52.5 (c 0.99,
D
CHCl3); 1H NMR (300 Mz, CDCl3) δ -0.07 (d, J ) 4.8 Hz, 6H),
0.82 (s, 9H), 1.57-1.75 (m, 3H), 1.92-2.10 (m, 1H), 2.48 (br-s,
1H), 2.78 (dd, J ) 7.8 and 15.2 Hz, 1H), 3.21 (t, J ) 9.8 Hz,
1H), 3.44 (dd, J ) 4.2 and 9.9 Hz, 1H), 3.52-3.65 (m, 1H),
3.80 (s, 3H). 6.37 (ddd, J ) 1.3, 2.8 and 7.7 Hz, 1H), 6.87 (d,
J ) 7.5 Hz, 1H), 7.05 (dt, J ) 0.8 and 7.9 Hz, 1H), 7.19-7.36
(m, 10H); 13C NMR (75 Mz, CDCl3) δ -5.3, -5.2, 18.3, 24.4,
26.0, 29.6, 52.6, 55.0, 64.0, 66.9 (d, J cp ) 5.3 Hz), 112.4, 124.9,
126.5, 128.2 (d, J cp ) 9.7 Hz), 128.2, 128.3 (d, J cp ) 9.6 Hz),
133.9 (d, J cp ) 20.5 Hz), 134.3 (d, J cp ) 21.2 Hz), 138.8 (d,
J cp ) 13.3 Hz), 139.1 (d, J cp ) 15.0 Hz), 141.3 (d, J cp ) 21.9
Hz), 142.3 (d, J cp ) 4.5 Hz), 157.9 (d, J cp ) 3.4 Hz); 31P NMR
(121 Mz, CDCl3) δ -15.7; FAB-MS m/z (rel intensity) 504
(M+ - 1, 30); HRMS (FAB-MS) m/z calcd for C30H40N2PSi +
H 506.2644, found 506.2599.
1
0.11, CHCl3); H NMR (300 Mz, CDCl3) δ 2.10-2.55 (m, 4H),
2.85-3.15 (m, 1H), 3.77 (dt, J ) 2.8 and 10.8 Hz, 1H), 3.89-
4.04 (m, 1H), 3.99 (s, 3H), 4.17 (dd, J ) 4.9 and 10.9 Hz, 1H),
4.57 (dd, J ) 7.7 and 7.8 Hz, 1H), 5.38 (dt, J ) 8.7 and 11.0
Hz, 1H), 6.86 (ddd, J ) 1.1, 7.8 and 9.6 Hz, 1H), 7.18 (d, J )
8.1 Hz, 1H), 7.32-7.64 (m, 7H), 7.70-7.84 (m, 2H), 7.84-8.00
(m, 2H); 13C NMR (75 Mz, CDCl3) δ 26.3, 30.4, 56.0, 66.9, 69.2,
76.8, 116.4, 117.3, 124.9, 126.2, 127.1, 128.6, 128.8, 129.0,
129.5, 130.4, 130.6 (d, J cp ) 8.8 Hz), 131.5, 131.9 (d, J cp ) 2.9
Hz), 132.2 (d, J cp ) 3.1 Hz), 133.9, 134.0, 149.2 (d, J cp ) 18.7
Hz), 153.5 (d, J cp ) 17.7 Hz); 31P NMR (121 Mz, CDCl3) δ 42.6;
FAB-MS m/z (rel intensity) 534 ([M - Cl]+ + 1, 100). Anal.
Calcd for C25H23Cl2NO2.5PPd: C, 50.74; H, 4.94; N, 2.37.
Found: C, 50.74; H, 4.94; N, 2.30.
(S)-1-[2′-(Dip h en ylp h osp h in o)-6′-m et h oxyp h en yl]-2-
[(1′′,1′′-d im eth yleth yl)d ip h en ylsila n oxym eth yl]p yr r oli-
d in e (10c). To a solution of (S)-1-[2′-(diphenylphosphino)-6′-
methoxyphenyl]-2-(hydroxymethyl)pyrrolidine 4e (0.12 g, 0.3
mmol) and imidazole (0.04 g, 0.6 mmol) in DMF (1 mL) was
added tert-butyldiphenylsilyl chloride (0.16 mL, 0.6 mmol) at
room temperature. The mixture was stirred for 4.5 h under
an argon atmosphere, diluted with ether, and quenched with
water. The organic layer was washed with brine, dried over
MgSO4, and concentrated under reduced pressure, and the
residue was purified by silica gel chromatography (elution with
P r ep a r a tion of P a lla d iu m Com p lex 11b. To a solution
of Pd(MeCN)2Cl2 (0.013 g, 0.05 mmol) in CHCl3 (0.5 mL) was
added (S)-1-[2′-(diphenylphosphino)-6′-methoxyphenyl]-2-(tri-
methylsilanoxymethyl)pyrrolidine 10a (0.023 g, 0.05 mmol) at
room temperature. The reaction mixture was stirred for 30
min under an argon atmosphere, filtered, and evaporated
under reduced pressure: 44%; mp 155-158 °C (dec); [R]25
D
1
+176.9 (c 0.1, CHCl3); H NMR (300 Mz, CDCl3) δ -0.22 (s,
n-hexane/EtOAc ) 40/1): 90%; [R]25 +35.8 (c 0.52, CHCl3);
3H), 2.12-2.45 (m, 3H), 3.06-3.28 (m, 1H), 3.66-3.92 (m, 2H),
3.99 (s, 1H), 4.09 (dd, J ) 5.6 and 10.0 Hz, 1H), 4.47 (dd, J )
7.4 and 10.0 Hz, 1H), 5.37 (dt, J ) 8.6 and 11.2 Hz, 1H), 6.91
(ddd, J ) 1.1, 7.9 and 9.4 Hz, 1H), 7.19 (d, J ) 8.1 Hz, 1H),
7.30-7.44 (m, 3H), 7.44-7.53 (m, 3H), 7.53-7.64 (m, 3H),
7.96-8.10 (m, 2H); 13C NMR (75 Mz, CDCl3) δ -0.9, 26.1, 31.1,
56.0, 66.2, 68.5, 77.0, 116.4, 117.1, 124.9, 126.3, 127.1, 128.6
D
1H NMR (300 Mz, CDCl3) δ 0.98 (s, 9H), 1.45-1.68 (m, 2H),
1.68-1.82 (m, 1H), 1.91-2.10 (m, 1H), 2.36 (br-s, 1H), 2.73
(dd, J ) 7.7 and 15.3 Hz, 1H), 3.43 (dt, J ) 0.6 and 10.6 Hz,
1H), 3.60-3.80 (m, 2H), 3.74 (s, 3H), 6.31 (ddd, J ) 1.2, 2.7
and 7.64 Hz, 1H), 6.83 (d, J ) 7.8 Hz, 1H), 6.95-7.12 (m, 3H),
7.12-7.18 (m, 3H), 7.18-7.42 (m, 11H), 7.50-7.63 (m, 4H);
6686 J . Org. Chem., Vol. 69, No. 20, 2004

Chiral (S)-Prolinol-Derived Ligands
(d, J cp ) 12.5 Hz), 128.9 (d, J cp ) 11.9 Hz), 129.3, 130.2, 130.6
and 11.0 Hz, 1H), 6.33 (dd, J ) 8.4 and 15.8 Hz, 1H), 7.19-
7.33 (m, 10H); 13C NMR (75 Mz, CDCl3) δ 13.8, 14.1, 49.2, 57.8,
61.4, 61.6, 126.4, 127.1, 127.5, 128.0, 128.5, 128.7, 129.4, 131.7,
136.9, 140.3, 167.4, 167.9; EI-MS m/z (rel intensity) 352 (M+,
29).
(d, J cp ) 8.6 Hz), 131.7 (d, J cp ) 3.1 Hz), 131.9, 132.2 (d, J cp
)
2.9 Hz), 132.6, 133.6 (d, J cp ) 11.2 Hz), 134.3 (d, J cp ) 10.8
Hz), 148.6 (d, J cp ) 18.9 Hz), 153.6 (d, J cp ) 17.5 Hz); 31P NMR
(121 Mz, CDCl3) δ 42.4; FAB-MS m/z (rel intensity) 604
([M - Cl]+, 98); HRMS (FAB-MS) m/z calcd for C27H34Cl2NO2-
PPdSi - Cl 604.0820, found 604.0841.
(S)-1′,1′-Dim eth yleth yl-2-ca r bo-1′′,1′′-d im eth yleth oxy-
3,5-d ip h en ylp en t -4-en oa t e (9d ):20 95% yield; 80% ee; mp
63-64 °C; [R]25D -9.3 (c 1.01, CHCl3); 1H NMR (300 Mz, CDCl3)
δ 1.22 (s, 9H), 1.47 (s, 9H), 3.73 (d, J ) 11.0 Hz, 1H), 4.15 (dd,
J ) 8.1 and 10.9 Hz, 1H), 6.33 (dd, J ) 8.1 and 15.8 Hz, 1H),
6.45 (d, J ) 15.8 Hz, 1H), 7.18-7.32 (m, 10H); 13C NMR (75
Mz, CDCl3) δ 27.6, 27.9, 49.0, 59.3, 81.5, 81.8, 126.3, 126.8,
127.3, 128.2, 128.4, 128.5, 130.1, 131.2, 137.1, 140.8, 166.7,
167.2; FAB-MS m/z (rel intensity) 409 (M+ + 1, 4).
P h en ylm et h yl-2-ca r b op h en ylm et h oxy-3,5-d ip h en yl-
Gr a d u a lly An a lyzed 1H NMR Sp ectr a of 11a In volvin g
Ad d ition of BSA by P or tion .22 To a solution of Pd(MeCN)2-
Cl2 (0.026 g, 0.1 mmol) in CDCl3 (0.6 mL) was added (S)-1-
[2′-(diphenylphosphino)-6′-methoxyphenyl]-2-(hydroxymethyl)-
pyrrolidine 4e (0.036 g, 0.1 mmol) at room temperature under
an argon atmosphere. After being stirred for 30 min, the
reaction mixture was displaced to a NMR tube and elucidated
by 1H NMR (300 Mz) analyses. To this solution was added the
solution of N,O-bis(trimethylsilyl)acetamide (BSA) in CDCl3
(0.063 mL, 0.025 mmol, 0.4 M). After being shaken, the
solution was elucidated by 1H NMR (300 Mz) analyses; this
action was repeated 4 times.
p en t-4-en oa te (9e):6x 90% yield; 95% ee; [R]25 -4.5 (c 1.07,
D
CHCl3); 1H NMR (300 Mz, CDCl3) δ 4.05 (d, J ) 10.9 Hz, 1H),
4.30 (dd, J ) 8.2 and 10.9 Hz, 1H), 4.92 (dd, J ) 12.3 and 14.2
Hz, 2H), 5.10 (dd, J ) 12.2 and 14.4 Hz, 2H), 6.30 (dd, 8.1
and 15.7 Hz, 1H), 6.42 (d, J ) 15.8 Hz, 1H), 6.97-7.08 (m,
2H), 7.11-7.33 (m, 18H); 13C NMR (75 Mz, CDCl3) δ 49.2, 57.7,
67.1, 67.3, 126.4, 127.1, 127.5, 127.9, 128.0, 128.1, 128.3, 128.3,
128.4, 128.5, 128.7, 128.9, 131.8, 135.0, 135.1, 136.7, 140.0,
167.1, 167.5; FAB-MS m/z (rel intensity) 477 (M+ + 1, 2).
(R)-Eth yl-2-ca r boeth oxy-2-m eth yl-3,5-d ip h en ylp en t-4-
en oa te (9f):14a 98% yield; 98% ee; [R]25D +41.1 (c 1.02, CHCl3);
1H NMR (300 Mz, CDCl3) δ 1.16 (t, J ) 7.1 Hz, 3H), 1.22 (t,
J ) 7.1 Hz, 3H), 1.47 (s, 3H), 4.07 (q, J ) 7.1 Hz, 2H), 4.18 (q,
J ) 7.1 Hz, 2H), 4.29 (d, J ) 8.9 Hz, 1H), 6.44 (d, J ) 15.8 Hz,
1H), 6.71 (dd, J ) 8.9 and 15.8 Hz, 1H), 7.18-7.34 (m, 10H);
13C NMR (75 Mz, CDCl3) δ 14.0, 14.0, 18.8, 53.7, 58.9, 61.4,
126.3, 127.1, 127.3, 128.2, 128.4, 128.9, 129.6, 132.6, 137.3,
139.5, 171.0, 171.2; EI-MS m/z (rel intensity) 366 (M+, 10).
Gen er a l P r oced u r e for P a lla d iu m -Ca t a lyzed Allylic
Alk yla tion . To a mixture of [Pd(η3-C3H5)Cl]2 (0.004 g, 0.01
mmol), chiral aminophosphine 4 or 10 (0.02 mmol), and
lithium acetate (0.001 g, 0.01 mmol) in a solvent (1 mL) were
added N,O-bis(trimethylsilyl)acetamide (BSA) (0.37 mL, 1.5
mmol), racemic allylic ester 7 (0.5 mmol), and 1,3-dicarbonyl
compound 8 (1.5 mmol) under an argon atmosphere. After
being stirred the corresponding times, the reaction mixture
was diluted with ether and quenched with saturated aqueous
NH4Cl. The organic layer was washed with brine, dried over
MgSO4, and concentrated under reduced pressure. The residue
was purified by silica gel chromatography.
(S)-Met h yl-2-ca r b om et h oxy-3,5-d ip h en ylp en t -4-en o-
a te (9a ):17 (Table 5, entry 6) 46% yield; 98% ee; [R]25 -20.6
D
(c 1.01, CHCl3); 1H NMR (300 Mz, CDCl3) δ 3.52 (s, 3H), 3.70
(s, 3H), 3.96 (d, J ) 11.0 Hz, 1H), 4.26 (dd, J ) 8.5 and 11.0
Hz, 1H), 6.32 (dd, J ) 8.5 and 15.8 Hz, 1H), 6.48 (d, J ) 15.8
Hz, 1H), 7.21-7.33 (m, 10H); 13C NMR (75 Mz, CDCl3) δ 49.2,
52.5, 52.7, 57.7, 126.4, 127.2, 127.6, 127.9, 128.5, 128.8, 129.1,
131.9, 136.8, 140.2, 167.8, 168.2; EI-MS m/z (rel intensity) 324
(M+, 11).
Ack n ow led gm en t. We thank Prof. Katsuyuki Ogu-
ra (Chiba University) for generously sharing their
Bruker DPX-300 system and Prof. Kentaro Yamaguchi
(Chemical Analysis Center, Chiba University) for per-
forming the X-ray diffraction analysis of 11a .
Meth yl-2-ca r bom eth oxy-3,5-bis(4′-ch lor op h en yl)p en t-
Su p p or tin g In for m a tion Ava ila ble: ORTEP diagrams
of 4e, 10a , and 11a ; gradually analyzed 1H NMR spectra of
11a involving addition of BSA by portion; copies of 1H, 13C,
and 31P NMR spectra of 4a , 4c-f, 5d , 6a , 6c-d , 10a -d , 11a ,
and 11b; copies of H-H and C-H COSY NMR spectra of 4e,
11a , and 11b; copies of 1H and 31P VT NMR spectra of 4e;
copies of 1H and 13C NMR spectra of 9a -f; copies of HPLC
charts of 9a -f; three X-ray crystallographic files in CIF format;
and ORTEP diagrams for 4e, 10a , and 11a . This material is
available free of charge via the Internet at http://pubs.acs.org.
4-en oa te (9b):6x,9n 79% yield; 93% ee; mp 65-68 °C; [R]25D -2.8
1
(c 1.12, CHCl3); H NMR (CDCl3) δ 3.54 (s, 3H), 3.70 (s, 3H),
3.91 (d, J ) 10.8 Hz, 1H), 4.25 (dd, J ) 8.4 and 10.7 Hz, 1H),
6.27 (dd, J ) 8.3 and 15.7 Hz, 1H), 6.41 (d, J ) 15.8 Hz, 1H),
7.15-7.35 (m, 8H); 13C NMR (CDCl3) δ 48.3, 52.5, 52.6, 57.3,
127.5, 128.6, 128.9, 129.1, 129.2, 131.0, 133.0, 133.3, 135.0,
138.4; EI-MS m/z (rel intensity) 392 (M+, 12).
(S)-Eth yl-2-car boeth oxy-3,5-diph en ylpen t-4-en oate (9c):
95% yield; 97% ee; [R]25 -17.2 (c 1.02, CHCl3); 1H NMR
19
D
(300 Mz, CDCl3) δ 1.01 (t, J ) 7.1 Hz, 3H), 1.21 (t, J ) 7.1 Hz,
3H), 3.90-4.01 (m, 3H), 4.17 (q, J ) 7.1 Hz, 2H), 4.26 (dd, 8.4
J O049469T
J . Org. Chem, Vol. 69, No. 20, 2004 6687