C O M M U N I C A T I O N S
vidual Research, 2002A-539). We thank Messrs. Akihiro Kinoshita
and Hatsuo Kawada for some early experiments.
Supporting Information Available: Experimental details and
characterization data for the products (PDF). This material is available
Figure 1. Application to the steroid side-chain synthesis.
Table 2. Recycling the Recovered Cr-Ligand 1 Complex
References
(1) (a) Okude, Y.; Hirano, S.; Hiyama, T.; Nozaki, H. J. Am. Chem. Soc.
1977, 99, 3179-3180. (b) Okude, Y.; Hiyama, T.; Nozaki, H. Tetrahedron
Lett. 1977, 3829-3832.
(2) Recent reviews: (a) Takai, K.; Nozaki, H. Proc. Jpn. Acad., Ser. B 2000,
76B, 123-131. (b) Fu¨rstner, A. Chem. ReV. 1999, 99, 991-1045. (c)
Wessjohann, L. A.; Scheid, G. Synthesis 1999, 1, 1-36. (d) Avalos, M.;
Babiano, R.; Cintas, P.; Jimenez, J. L.; Palacios, J. C. Chem. Soc. ReV.
1999, 28, 169-177.
entry
product
R
ee(%)a,b
yield(%)c
time(h)
recycling
(3) (a) Fu¨rstner, A.; Shi, N. J. Am. Chem. Soc. 1996, 118, 12349-21357. (b)
Fu¨rstner, A.; Shi, N. J. Am. Chem. Soc. 1996, 118, 2533-2536.
(4) (a) Bandini, M.; Cozzi, P. G.; Melchiorre, P.; Morganti, S.; Umani-Ronchi,
A. Org. Lett. 2001, 3, 1153-1155. (b) Bandini, M.; Cozzi, P. G.; Umani-
Ronchi, A. Pure Appl. Chem. 2001, 73, 325-329. (c) Bandini, M.; Cozzi,
P. G.; Umani-Ronchi, A. Tetrahedron 2001, 57, 835-843. (d) Bandini,
M.; Cozzi, P. G.; Umani-Ronchi, A. Polyhedron 2000, 19, 537-539. (e)
Bandini, M.; Cozzi, P. G.; Umani-Ronchi, A. Angew. Chem., Int. Ed. 2000,
39, 2327-2330. (f) Bandini, M.; Cozzi, P. G.; Melchiorre, P.; Morganti,
S.; Umani-Ronchi, A. Angew. Chem., Int. Ed. 1999, 38, 3357-3359.
(5) Asymmetric allylations not via a catalytic process: (a) Sugimoto, K.;
Aoyagi, S.; Kibayashi, C. J. Org. Chem. 1997, 62, 2322-2323. (b) Chen,
C.; Tagami, K.; Kishi, Y. J. Org. Chem. 1995, 60, 5386-5387. (c) Cazes,
B.; Verniere, C.; Gore´, J. Synth. Commun. 1983, 13, 73-79.
(6) See Supporting Information for the preparation of 1.
1d
2d
3
2a
2a
2e
2e
Ph
Ph
c-C6H11
c-C6H11
92(S)e
93(S)e
95(S)e
94(S)e
86
79
84
90
24
24
16
16
first time
second time
first time
4
second time
a-d See the footnotes to Table 1. e See ref 19a.
Scheme 1. Enantioselective Crotylation of Benzaldehyde
(7) Precedently developed C2-symmetrical tridentate ligands, for pybox: (a)
Nishiyama, H.; Sakaguchi, H.; Nakamura, T.; Horihata, M.; Kondo, M.;
Itoh, K. Organometallics 1989, 8, 846-848. For DBFOX: (b) Kanemasa,
S.; Oderaotoshi, Y.; Yamamoto, H.; Tanaka, J.; Wada, E.; Curran, D. P.
J. Org. Chem. 1997, 62, 6454-6455. Unfortunately, satisfactory results
for the enantioselective Nozaki-Hiyama allylations were not obtained
with these ligands.
(8) (a) Cahiez, G.; Chavant, P. Y. Tetrahedron Lett. 1989, 7373-7376. (b)
Hiyama, T.; Sawahata, M.; Obayashi, M. Chem. Lett. 1983, 1237-1238.
(9) N-ethylpiperidine, triethylamine, and tri-n-butylamine were also effective
for this highly enantioselective reaction, but the yields were slightly
lowered.
(10) For experimental procedure, see Supporting Information.
(11) Low temperature (0 °C) did not increase the enantioselectivity in other
reactions except entry 7.
(12) (a) In the absence of CrCl2 and ligand 1, the allylated products were
obtained in 8 and 14% yield under the conditions of entries 2 and 7,
respectively. Aliphatic aldehydes are surmised to be rather inert to
allylmanganase reagent. Cf. ref 3.
products in the recycling experiments are almost unchanged from
the values in entry 2 (93% ee) and entry 8 (94% ee) of Table 1,
respectively.
The diastereoselectivity of the reaction of benzaldehyde with
crotylbromide was somewhat lower than that observed in the
absence of ligand 1 (Scheme 1).16 The reaction was anti-selective
and the enantioselectivities were 75% ee (anti-form) and 21% ee
(syn-form).17
Configuration of the major enantiomer of anti-5 was (1S,2S),
showing that benzaldehyde preferentially reacted from its si-face.18
This si-face selectivity can be seen in Table 1 where 2d, 2f, and 2j
have (R)-configuration, and others have (S)-configuration, revealing
that all aldehydes reacted predominantly from their si-face.
The anti-selectivity noted above is not high enough to indicate
the cyclic Zimmermann-Traxler-like transition state, which may
account for the si-face selectivity. Thus, an acyclic transition state
cannot be ruled out. Hence, we are currently investigating the
reaction mechanism.20
In summary, a tridentate ligand 1 effective for the asymmetric
catalysis of Nozaki-Hiyama allylation and methallylation has been
developed. Ligand 1 is thought to form a chiral Cr complex with
CrCl2 in which ligand 1 is firmly bound to chromium. This complex
possesses great potential as the asymmetric catalyst for other Cr-
mediated reactions. Furthermore, there are numerous possibilities
of developing other asymmetric catalysts using an alternative metal,
because ligand 1 is able to incorporate other metal ions. Moreover,
immobilization of the Cr-ligand 1 complex is interesting because
the Cr-ligand 1 complex is water-tolerant and can be recycled.
(13) (a) Johnson, W. S.; Chan, M. F. J. Org. Chem. 1985, 50, 2598-2600. (b)
Nakada, M.; Urano, Y.; Kobayashi, S.; Ohno, M. Tetrahedron Lett. 1994,
35, 741-744.
(14) CrCl2 (20 mol %), ent-ligand 1 (20 mol %), Mn (4.0 equiv), methallyl
chloride (2.0 equiv), and DIPEA (1.0 equiv) were used. Without ent-
ligand 1, the reaction proceeded sluggishly. The details will be com-
municated.
(15) Characterization of the recovered Cr-ligand 1 complex is now under
investigation.
(16) The same condition for the enantioselective allylation was used.
(17) Anti/syn ratio, ee, and absolute configuration of the major enantiomers
1
were determined by 600 MHz H NMR and HPLC of Mosher’s ester of
7; see ref 4e. Yields were the combined yield.
(18) (a) Enantioselectivity and yield of the crotylation of benzaldehyde increased
to 77% ee (anti-form), 26% ee (syn-form), and 53% combined yield when
the reaction was carried out at 0 °C.
(19) (a) Riediker, M.; Duthaler, R. O. Angew. Chem., Int. Ed. Engl. 1989, 28,
494-495. (b) Yanagisawa, A.; Nakashima, H.; Yamamoto, H. J. Am.
Chem. Soc. 1996, 118, 4723-4724. (c) Wang, Z.; Wang, D.; Sui, X. Chem.
Commun.1996, 2261-2262. (d) Hoffmann, R. W.; Herold, T. Chem. Ber.
1981, 114, 375-383. (e) Kinugasa, M.; Harada, T.; Egusa, T.; Fujita, K.;
Oku, A. Bull. Chem. Soc. Jpn. 1996, 69, 3639-3650. (f) Johnson, W. S.;
Crackett, P. H.; Elliot, J. D.; Jagodzinski, J. J.; Lindell, S. D.; Natarajan,
S. Tetrahedron Lett. 1989, 25, 7373-7376. (g) Ishihara, K.; Mouri, M.;
Gao, Q.; Maruyama, T.; Furuta, K.; Yamamoto, H. J. Am. Chem. Soc.
1993, 115, 11490-11495.
(20) An additional interesting feature of this reaction is that no pinacol product
(cf. ref 4) was found in the all reactions reported here.
Acknowledgment. This work was financially supported in part
by Waseda University Grant for Special Research Projects (Indi-
JA021243P
9
J. AM. CHEM. SOC. VOL. 125, NO. 5, 2003 1141