C O M M U N I C A T I O N S
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interesting to note that these two substitute patterns lead to
completely reversed enantioface selection as shown in Table 2.
Entries 1 and 2 indicated that, without (Z)-substituent, the epoxi-
dation gave (3R)-product predominately, while entries 7 and 8
showed (Z)-substituted substrates mainly provided (3S,4R)-products.
The reactivity of epoxidation of bishomoallylic alcohols was
lower as the length of the carbon chain was increased, requiring
10 mol % of catalyst in most cases. The best substrates for this
reaction are 1,1-disubstituted olefins bearing an aromatic group as
shown in Table 3. We anticipated that making the δ-carbon a
benzylic position would accelerate the THF forming process;
however, in most cases, the δ-aromatic group actually suppressed
the THF formation in that we were able to isolate a high yield of
corresponding epoxides. Several bishomoallylic alcohols bearing
a δ-aromatic group were subjected to the optimized conditions, and
they underwent smooth reactions. Electron-deficient substrates such
as 4b, 4c, and 4d provide corresponding epoxides efficiently (entries
2, 3, and 4). Electron-rich but sterically hindered substrate 4e gave
epoxide in high ee but low reactivity, presumably due to the size
of the ortho-methoxy group which is very close to the double bond
(entry 5). Substrate 4g which contains a para-methoxyphenyl
substituent was converted to THF products with lower ee presum-
ably because the para-methoxy effect stabilizes the benzylic cation
therefore facilitating the SN1 type racemizing cyclization. (Z)-
Substituted substrates such as 4h also exhibited high enantioselec-
tivity although the reactivity was much lower. THF formation was
also exclusively observed in this reaction.
(3) (a) Makita, N.; Hoshino, Y.; Yamamoto, H. Angew. Chem., Int. Ed. 2003,
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Int. Ed. 2008, 47, 7520; Angew. Chem. 2008, 120, 7630. Some chiral BHA
ligands such as 1a, 1b and those described in ref 3d have been
commercialized and readily available from Sigma-Aldrich Co. and Tokyo
Chemical Industry.
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G.; Vranesic, B.; Okigawa, M.; Smith-Palmer, T.; Kishi, Y. J. Am. Chem.
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Shibasaki, M. J. Am. Chem. Soc. 2001, 123, 1256.
In conclusion, we discovered that, in combination with BHA
ligands, Zr(IV) and Hf(IV) are able to catalyze highly enantio-
selective epoxidation of homoallylic alcohols and bishomoallylic
alcohols in a very efficient manner. Further efforts are being
employed to investigate the reaction mechanism and potential
application in asymmetric synthesis.
(9) Lubben, T. V.; Wolczanski, P. T. J. Am. Chem. Soc. 1987, 109, 424.
(10) Ti-polymeric aggregates: (a) Martin, R. L.; Winter, G. Nature 1963, 197,
687. (b) Russo, W. R.; Nelson, W. H. J. Am. Chem. Soc. 1970, 92, 1521.
Evidence for Zr-polymeric species: (c) Bradley, D. C.; Holloway, C. E.
J. Chem. Soc. A 1968, 1316.
(11) It is probably due to a stable complex Zr(BHA)2 was formed. See:
Fouche´, K. F.; le Roux, H. J.; Phillips, F. J. Inorg. Nucl. Chem. 1970,
32, 1949.
(12) Vogl, E. M.; Gro¨ger, H.; Shibasaki, M. Angew. Chem., Int. Ed. 1999, 38,
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Acknowledgment. National Institutes of Health (NIH) is greatly
appreciated for providing financial support (GM068433-05).
(13) (a) Hanson, R. M.; Sharpless, K. B. J. Org. Chem. 1986, 51, 1922. (b)
Gao, Y.; Klunder, J. M.; Hanson, R. M.; Masamune, H.; Ko, S. Y.;
Sharpless, K. B. J. Am. Chem. Soc. 1987, 109, 5765. We also examined 3
Å and 5 Å MS as additive. No significant rate or ee improvement was
observed with 3 Å MS, while 5 Å MS favored the formation of THF
compounds.
Supporting Information Available: Representative experimental
procedures and necessary characterization data for all compounds are
provided. Results of nonlinear effect experiments are provided. This
References
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