strong steric hindrance effect of the ortho-substitutents, which
weakened the coordination of the aldehyde and consequently
lowered the enantioselectivity of reaction. These results are
consistent with Chan et al’s report about asymmetric alkylation
of aromatic aldehydes with triethylaluminium.4 The precise
structure of the catalyst is not clear at present. An investigation
of the mechanism is underway.
T. Itoh, T. Shirasaka and H. Yamamoto, J. Am. Chem. Soc., 1988, 110,
10; (h) A. Togni, Organometallics, 1990, 9, 3106; (i) A. K. Ghosh, P.
Mathivanan, J. Cappiello and K. Krishnan, Tetrahedron: Asymmetry,
996, 7, 2165; (j) S. Matsukawa and K. Mikami, Tetrahedron:
Asymmetry, 1997, 8, 815; (k) A. K. Ghosh, P. Mathivanan and J.
Cappiello, Tetrahedron Lett., 1997, 38, 2427; (l) H. Furuno, T.
Hanamoto, Y. Sugimoto and J. Inanaga, Org. Lett., 2000, 2, 49.
D. J. Cram, R. C. Helgeson, S. C. Peacock, L. J. Kaplan, L. A. Domeier,
P. Moreau, K. Koga, J. M. Mayer, Y. Chao, M. G. Siegel, D. H. Hoffman
and G. D. Y. Sogah, J. Org. Chem., 1978, 43, 1930.
3
1
3
In conclusion, we have developed a new, highly efficient
method for the synthesis of chiral 2-substitutent-2,3-dihydro-
4
H-pyran-4-one from aldehydes and Danishefsky’s diene using
4 A. S. C. Chan, F. Y. Zhang and C. W. Yip, J. Am. Chem. Soc., 1997, 119,
4080.
3
8
chiral H -BINOL-Ti(IV). High levels of enantioselectivity in
5
6
A series of solvents was screened including toluene, TBME, CH
DMF, Et O and THF.
A typical experimental procedure is given for the synthesis of (R)-
-phenyl-2,3-dihydro-4H-pyran-4-one: a mixture of (R)-H -BINOL
16.2 mg, 0.055 mmol), 1 M Ti(O-i-Pr) in CH Cl (50 ml, 0.05 mmol),
2 2
Cl ,
the synthesis of 2-substitutent-2,3-dihydro-4H-pyran-4-one
with wide substrate generality were obtained according to this
reaction.
We are grateful for the financial support from the National
Science Foundation of China (No. 29832020).
2
2
8
(
4
2
2
and activated powdered 4 Å molecular sieves (120 mg) in toluene (1 ml)
was heated at 35 °C for 1 h. The yellow mixture was cooled to rt, and
benzaldehyde (26 ml, 0.25 mmol) was added. The mixture was stirred for
1
0 min and cooled to 0 °C. Danishefsky’s diene (60 ml, 0.30 mmol) was
Notes and references
added. The mixture was stirred at 0 °C for 24 h, then it was treated with
5 drops of TFA. After the mixture was stirred for 15 min at 0 °C, saturated
1
For reviews, see: (a) S. J. Danishefsky, Chemtracts, 1989, 273; (b) S. J.
Danishefsky and M. P. De Ninno, Angew. Chem., Int. Ed. Engl., 1987, 26,
3
NaHCO (1.5 ml) was added, the mixture was then stirred for 10 min and
1
5; (c) S. J. Danishefsky, Aldrichimica Acta, 1986, 19, 59; for application
in total synthesis (d) J. D. Rainier, S. P. Allwein and J. M. Cox, Org. Lett.,
000, 2, 231.
(a) E. J. Corey, C. L. Cywin and T. D. Roper, Tetrahedron Lett., 1992, 33,
907; (b) G. E. Keck, X. Y. Li and D. Krishnamurthy, J. Org. Chem.,
995, 60, 5998; (c) S. E. Schaus, J. Brånalt and E. N. Jacobsen, J. Org.
filtered through a plug of Celite. The organic layer was separated, and the
aqueous layer was extracted with ether (5 3 3 ml), the combined organic
2 4
layers were dried over Na SO and concentrated. The crude residue was
purified by flash chromatography (petroleum ether–ethyl acetate, 4+1) to
yield (R)-2-phenyl-2,3-dihydro-4H-pyran-4-one (40 mg, 0.23 mmol,
92% yield) as a clear oil. The isolated material was determined to be in
97% ee by chiral GC analysis (cyclodex-b, 159 °C, 20 min, isothermal,
S R
t (minor) = 14.43 min, t (major) = 14.66 min).
7 1-Methoxy-3-(trimethylsilyloxy)buta-1,3-diene was purchased from
Lancaster with 95% content.
2
2
6
1
Chem., 1998, 63, 403; (d) Q. Z. Gao, T. Maruyama, M. Mouri and H.
Yamamoto, J. Org. Chem., 1992, 57, 1951; (e) K. Mikami, O. Kotera, Y.
Motoyama and H. Sakaguchi, Synlett, 1995, 975; (f) T. Hanamoto, H.
Furuno, Y. Sugimoto and J. Inanaga, Synlett, 1997, 79; (g) K. Maruoka,
1606
Chem. Commun., 2000, 1605–1606