C O M M U N I C A T I O N S
Scheme 3. Ru-Catalyzed AROM/CM of 7-Oxonorbornenes
Scheme 2. Activity and Recyclability of Chiral Ru Catalyst 3
Table 1. Ru-Catalyzed AROM/CM of Tricyclic Norbornenesa
combinatorial synthesis.4 Investigation of Ru-catalyzed asymmetric
ring-closing metatheses and study of other metal complexes of the
new chiral imidazolinium ligands are in progress.
Acknowledgment. We dedicate this paper to our colleague,
Professor T. Ross Kelly, on the occasion of his 60th birthday.
Financial support from the NSF (CHE-9905806 and a predoctoral
fellowship to J.S.K.) is gratefully acknowledged. We thank Dr.
Richard Staples and Jarred Blank for assistance in determining the
X-ray structure of 3.
temp (°C);
time (h)
conv (%)b;
yield (%)c
recov.
ee
entry
R
cat. (%)c
trans:cisb
(%)d
1
2
3
Ph
a
b
c
50; 1.0
50; 1.5
50; 1.0
>98; 71
>98; 57
>98; 60
96
92
88
>98: 2
>98: 2
>98: 2
80
>98
>98
n-C5H11
Cy
a Conditions: 5 equiv of terminal olefin in entry 1 and 2 equiv in entries
2 and 3; THF, under N2. b By 400 MHz 1H NMR analysis. c Isolated yields
after chromatography. d By chiral HPLC (see the Supporting Information).
Supporting Information Available: Experimental procedures and
spectral and analytical data for the chiral catalyst and reaction products
(PDF). This material is available free of charge via the Internet at http://
pubs.acs.org.
activity.10,12 As illustrated in Scheme 2,13 catalyst 3 can be recovered
in high yield by silica gel chromatography. Upon isolation, 3 may
be reused without significant loss of activity. For example, the
catalyst recovered from the synthesis of 10 effects RCM of 9 again
with equal facility (93% conversion, 48 h) and provides the desired
product in 90% isolated yield (78% recovered catalyst). It should
be noted that conversion of 11 to 12 cannot be promoted with Mo-
based catalysts (<10% conversion).14
References
(1) For a recent review of catalytic metathesis, see: Furstner, A. Angew.
Chem., Int. Ed. 2000, 39, 3012-3043.
(2) (a) Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus, P. J., Jr.; Hoveyda, A.
H. J. Am. Chem. Soc. 1999, 121, 791-799. (b) Garber, S. B.; Kingsbury,
J. S.; Gray, B. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122, 8168-
8179.
(3) (a) Cossy, J.; BouzBouz, S.; Hoveyda, A. H. J. Organomet. Chem. 2001,
624, 327-332. (b) Imhof, S.; Randl, S.; Blechert, S. Chem. Commun.
2001, 1692-1693. For an application of 2 in target-oriented synthesis,
see: (c) BouzBouz, S.; Cossy, J. Org. Lett. 2001, 3, 1451-1454.
(4) For a glass-supported variant of 2, see: Kingsbury, J. S.; Garber, S. B.;
Giftos, J. M.; Gray, B. L.; Okamoto, M. M.; Farrer, R. A.; Fourkas, J. T.;
Hoveyda, A. H. Angew. Chem., Int. Ed. 2001, 40, 4251-4255.
(5) For an overview of catalytic asymmetric metathesis, see: Hoveyda, A.
H.; Schrock, R. R. Chem. Eur. J. 2001, 7, 945-950.
(6) (a) Alexander, J. B.; La, D. S.; Cefalo, D. R.; Hoveyda, A. H.; Schrock,
R. R. J. Am. Chem. Soc. 1998, 120, 4041-4042. (b) Zhu, S.; Cefalo, D.
R.; La, D. S.; Jamieson, J. Y.; Davis, W. M.; Hoveyda, A. H.; Schrock,
R. R. J. Am. Chem. Soc. 1999, 121, 8251-8259. (c) Cefalo, D. R.; Kiely,
A. F.; Wuchrer, M.; Jamieson, J. Y.; Schrock, R. R.; Hoveyda, A. H. J.
Am. Chem. Soc. 2001, 123, 3139-3140.
(7) (a) Weatherhead, G. S.; Ford, J. G.; Alexanian, E. J.; Schrock, R. R.;
Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122, 1828-1829. (b) La, D. S.;
Sattely, E. S.; Ford, J. G.; Schrock, R. R.; Hoveyda, A. H. J. Am. Chem.
Soc. 2001, 123, 7767-7778.
(8) For a recent example of Ru-catalyzed asymmetric RCM, see: Seiders, T.
J.; Ward, D. W.; Grubbs, R. H. Org. Lett. 2001, 3, 3225-3228.
(9) For a review of complexes chiral at the metal, see: Brunner, H. Angew.
Chem., Int. Ed. 1999, 38, 1194-1208.
(10) Chang, S.; Jones, L.; Wang, C.; Henling, L. M.; Grubbs, R. H.
Organometallics 1998, 17, 3460-3465.
Initial studies indicate that 3 is an effective and practical chiral
catalyst for enantioselective metathesis. Several examples of Ru-
catalyzed AROM/CM are depicted in Table 1. As illustrated in entry
1, treatment of 13 with 5 equiv of styrene in the presence of 10
mol % 3 in THF (50 °C)15 leads to the formation of 14a in 80% ee
and 71% isolated yield (>98% trans). Ru-catalyzed AROM/CM
of 13 is exceptionally selective with aliphatic olefins. With
1-heptene and sterically bulky vinylcyclohexane (entries 2-3),
14b,c are obtained in >98% ee, >98% trans, and 57-60% yield.
Several additional issues regarding the reactions in Table 1 merit
mention: (i) The chiral catalyst can be recovered after chroma-
tography (88-96% yield). (ii) Byproducts from homodimerization
of the terminal olefins or additional cross metathesis (CM) of 14a,c
1
to afford meso dienes are not observed (<5%, H NMR).7b (iii)
Recovered 3 can be reused without significant loss of enantiose-
lectivity and with similar reactivity.16 (iv) None of the transforma-
tions can be effected with chiral Mo-based catalysts, which would
rapidly polymerize substrates such as 13 (no AROM/CM product
even with >10 equiv terminal olefin).7b
The catalytic AROM/CM reactions in Scheme 3 further underline
the significant potential of chiral Ru complex 3 in enantioselective
synthesis. Transformation of 15a is catalyzed by 5 mol % 3 at room
temperature, in air, and with undistilled and nondegassed THF to
deliver 16a17 in 96% ee and 66% isolated yield (>98% trans). More-
over, with only 0.5 mol % 3, 15b reacts in 75 min to afford 16b in
95% ee and 76% yield (>98% trans). It should be noted that the
reactions shown in Table 1, carried out at 50 °C, can also be run
in air without significant change in reactivity or enantioselectivity.
Ongoing research involves the development of additional chiral
Ru catalysts and their supported variants for use in enantioselective
(11) Optically pure 4 was synthesized by modification of a reported procedure
in seven steps from commercially available materials. See: Ito, Y.; Miyake,
T.; Hatano, S.; Shima, R.; Ohara, T.; Suginome, M. J. Am. Chem. Soc.
1998, 120, 11880-11893.
(12) Dias, E. L.; Nguyen, S. T.; Grubbs, R. H. J. Am. Chem. Soc. 1997, 119,
3887-3897.
(13) Studies on catalytic enantioselective RCM of 11 and related substrates
are in progress.
(14) Unpublished results of D. S. La and A. F. Kiely.
(15) Reduced enantioselectivity is observed in reactions of 13 at lower
temperatures.
(16) For example, formation of 14b is catalyzed with recycled 3 in >98% ee
and 46% yield (86% recovered 3).
(17) The identity of the major enantiomer of 16a was established by comparison
with authentic materials (see the Supporting Information); the remaining
assignments are by inference.
JA020259C
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J. AM. CHEM. SOC. VOL. 124, NO. 18, 2002 4955