H. Furuno et al. / Tetrahedron Letters 43 (2002) 8297–8299
Table 2. Asymmetric double aldol reaction of (R)-7 with aldehydes
8299
Entry
Aldehyde
Product (yield%)
Entry
Aldehyde
Product (yield%)
1
2
3
4
5
Benzaldehyde
Tolualdehyde
1-Naphthaldehyde
2-Naphthaldehyde
4-MeO-C6H4CHO
9a (93)
9b (95)
9c (85)a
9d (93)
9e (71)b
6
7
8
4-CF3-C6H4CHO
4-Br-C6H4CHO
Methacrolein
Isobutyraldehyde
Isobutyraldehyde
9f (94)
9g (98)
9h (81)c
9
9i (72)d
10e
13i (95; 3.3:1)
a 12c (11%).
b 12e (22%).
c 12h (8%).
d 12i (6%), 13i (20%).
e c-Hex2BOTf/Et3N were used as enolization reagents.
Acknowledgements
during 20 min, and the mixture was stirred at 0°C for 15
min. Benzaldehyde (12.7 g, 120 mmol) was added drop-
wise, and the reaction was let to warm to room tempera-
ture and stirred for 1.5 h. A pH 7 buffer solution (200 ml)
was added and the organic layer was separated. Aqueous
layer was extracted with CH2Cl2 (2×100 ml) and the
combined organic extracts were concentrated under vac-
uum. The residue was diluted with MeOH (150 ml) and
tartaric acid (30 g) was added. To the mixture, 30% H2O2
solution (100 ml) was carefully added with cooling in an
ice-water bath. After exothermic reaction subsided, the
mixture was stirred at room temperature for 1 h and
concentrated. Usual extractive workup afforded 9 (16.0 g,
37 mmol, 93%) after crystallization from ethyl acetate
and hexane.
This work was supported by a grant from the Ministry
of Education, Culture, Sports, Science and Technology
of Japan (Grant-in-Aid 10640578 and 13640533).
References
1. Abiko, A.; Liu, J.-F.; Buske, D. C.; Moriyama, S.; Masa-
mune, S. J. Am. Chem. Soc. 1999, 121, 7168.
2. Abiko, A.; Inoue, T.; Masamune, S. J. Am. Chem. Soc.
2002, 124, 10759.
3. Abiko, A.; Inoue, T.; Furuno, H.; Schwalbe, H.; Fieres,
C.; Masamune, S. J. Am. Chem. Soc. 2001, 123, 4605.
4. (a) Evans, D. A. Aldrichim. Acta 1982, 15, 23; (b) Cow-
den, C. J.; Paterson, I. Org. React. 1997, 51, 1.
5. (a) Evans, D. A.; Bartroli, J.; Shih, T. L. J. Am. Chem.
Soc. 1981, 103, 2127; (b) Loubinoux, B.; Sinnes, J.-L.;
O’Sullivan, A. C.; Winkler, T. Tetrahedron 1995, 51,
3549; (c) Yan, T.-H.; Hung, A.-W.; Lee, H.-C.; Chang,
C.-S.; Liu, W.-H. J. Org. Chem. 1995, 60, 3301.
6. Compound 6b shows the following spectroscopic proper-
ties: 1H NMR: l 4.00 (1H, s), 4.11 (2H, t, J=8.5 Hz),
4.65 (2H, t, J=8.5 Hz), 8.16 (2H, s, NH); 13C NMR: l
33.4, 44.4, 64.8, 85.0, 156.6, 159.4; 11B NMR: l 50.5,
70.4; [13C, 1H] COSY 33.4–1.7, 44.4–4.11, 64.8–4.65,
85.0–4.00; [1H, 13C] HMBC ꢀ1.7–85.0, 4.00–33.4, 4.00–
156.6, 4.11–64.8, 4.11–159.4, 4.65–44.4, 4.65–159.4.
7. Typical reaction procedure: Commercial solution of n-
Bu2BOTf in CH2Cl2 (Aldrich, 1 M, 100 ml) was trans-
ferred to CH2Cl2 (200 ml) via cannula and then Et3N
(120 mmol) was added dropwise. To this solution, (R)-7
(8.80 g, 40 mmol) in CH2Cl2 (20 ml) was added at 0°C
8. HA appeared at l 5.14 as a double doublet (J=8.2, 10.0
Hz).
9. The absolute stereochemistry of the double aldol prod-
ucts were assigned on the analogy of that of 9a.
10. 1H NMR showed the increase of the enolate of
isobuyraldehyde was accompanied with the consumption
of 8b and isobutyraldehyde, and formation of the (mono)
aldolate. Thus, the mono aldol product is attributed to
the reversion of 8b to the mono enolate by proton
transfer. See Ref. 2.
11. The following chiral triols of C3-symmetry [HC(CH(OH)-
R)3] have been synthesized: R=4-Me-C6H4, mp 119–
120°C, [h]2D2=131.8 (c 1.24); R=4-MeO-C6H4, mp 203–
204°C, [h]2D2=119.4 (c 0.50); R=4-Br-C6H4, mp
172–173°C, [h]D22=177.9 (c 1.00); R=4-CF3-C6H4, mp
130–131°C, [h]2D2=39.8 (c 0.50); R=1-naphthyl, mp 233–
234°C, [h]2D2=−407.3 (c 1.00); R=2-naphthyl, mp 156–
157°C, [h]2D2=342.6 (c 1.00). Details of the synthesis will
be reported elsewhere.