P. Radha Krishna et al. / Tetrahedron Letters 45 (2004) 7847–7850
7849
CN
O
(COCl)2
O
O
O
O
O
OH
DMSO, Et3N
CH2Cl2, -78 ˚C
DABCO
DMF, rt, 48 h
55%
CN
CHO
OH
8
9
(+)-DIPT
Ti-(O-i-Pr)4
Cumene H2O2, 4 Å MS
O
O
O
O
O
+
CN
CN
Dry CH2Cl2, -20 ˚C
OH
OH
(S)-9, 35%
(S)-4b (anti), 39%
(+)-DIPT, Ti-(O-i-Pr)4
Cumene H2O2, 4 Å MS
Dry CH2Cl2, -20 ˚C
O
O
O
CN
(S)-9
OH
(R)-4b (syn), 72%
Scheme 3.
4. Katsuki, T.; Shapless, K. B. J. Am. Chem. Soc. 1980, 102,
5974–5976.
The increased reactivity of the 2,3-epoxy aldehydes in
the Baylis–Hillman coupling, compared to that of allylic
aldehyde 8, can be explained by the presence of a more
electronegative oxygen atom in the epoxide ring making
the adjacent carbonyl carbon more electrophilic. The
diastereoselectivity in the formation of Baylis–Hillman
adduct 7b was increased from 72% to 84% when the
reaction was conducted at À20ꢁC in DMF, though the
rate of the reaction was slower.
5. (a) Radha Krishna, P.; Kannan, V.; Ilangovan, A.;
Sharma, G. V. M. Tetrahedron: Asymmetry 2001, 12,
829–837; (b) Radha Krishna, P.; Kannan, V.; Sharma, G.
V. M.; Ramana Rao, M. H. V. Synlett 2003, 888–890; (c)
Radha Krishna, P.; Kannan, V.; Narasimha Reddy, P. V.
Adv. Synth. Catal. 2004, 346, 603–606.
6. (a) Mancuso, A. J.; Huang, S.-L.; Swern, D. J. Org. Chem.
1978, 43, 2480–2482; (b) Omura, K.; Swern, D. Tetrahe-
dron 1978, 34, 1651–1660.
7. Yu, C.; Liu, B.; Hu, L. J. Org. Chem. 2001, 66, 5413–5418.
8. (a) Cornforth, J. W.; Cornforth, R. H.; Mathew, K. K. J.
Am. Chem. Soc. 1959, 81, 112–127; (b) Evans, D. A.;
Siska, S. J.; Cee, V. C. Angew. Chem., Int. Ed. 2003, 42,
1761–1765.
9. (a) Mihelich, E. D. Tetrahedron Lett. 1979, 37, 1343–1346;
(b) Martin, V. S.; Woodard, S. S.; Katsuki, T.; Yamada,
Y.; Ikeda, M.; Sharpless, K. B. J. Am. Chem. Soc. 1981,
103, 6237–6240; (c) Roush, W. R.; Brown, R. J. J. Org.
Chem. 1983, 48, 5093–5101; (d) Hwang, G.-I.; Chung,
J.-H.; Lee, W. K. J. Org. Chem. 1996, 61, 6183–6188.
10. In general it was observed that the 1H NMR spectra of the
adducts resulting from the trans 2,3-epoxy aldehydes
showed the allylic proton (both for syn- and anti-isomers)
resonating downfield when compared to the adducts
obtained from cis-2,3-epoxy aldehydes.
In conclusion, we have demonstrated for the first time
the use of chiral 2,3-epoxy aldehydes in Baylis–Hillman
reactions to generate chiral epoxy alcohols with an
a-methylene group, in good yields and selectivity.11,12
The Cornforth model clearly suggests that the cis epox-
ides give syn-adducts as major compounds while the
trans epoxides resulted in anti-adducts as major prod-
ucts under standard base-catalyzed conditions. Interest-
ingly, this protocol can also be extrapolated to the other
isomeric epoxy aldehydes. Thus, chemically more sensi-
tive substrates can be useful as electrophiles in the Bay-
lis–Hillman reaction. Further work on the use of these
adducts is in progress.
11. General experimental procedure: To a cold solution (0ꢁC)
of epoxy aldehyde (1mmol) in DMF were added DABCO
(0.5mmol) and the activated alkene (1.5mmol) and the
mixture stirred for 3–8h at room temperature. After
completion of reaction (by TLC), the reaction mixture was
partitioned between diethyl ether (2 · 50mL) and water
(1 · 60mL). The organic phase was washed with brine
(2 · 50mL), dried (Na2SO4) and evaporated under
reduced pressure. The residue was purified by column
chromatography (silica gel, 8.5:1.5–8:2, n-hexane–EtOAc)
to afford products 1a, 2b, 3a,b, 4a,b, 5a,b, 6a,b, and 7a,b
in good yields (61–80%).
Acknowledgements
Two of the authors (K.R.L. and V.K.) thank CSIR, New
Delhi for financial support in the form of fellowships.
References and notes
1. (a) Basavaiah, D.; Rao, P. D.; Hyma, R. S. Tetrahedron
1996, 52, 8001–8062; (b) Ciganek, E. The Morita–Baylis–
Hillman reaction. In Org. React.; Paquette, L. A., Ed.;
John Wiley & Sons: New York, 1997; Vol. 51, pp 201–350;
(c) Basavaiah, D.; Rao, A. J.; Satyanarayana, T. Chem.
Rev. 2003, 103, 811–891.
12. Spectral data for selected compounds: Compound 4a: Pale
25
yellow syrup; ½aꢀD +42.6 (c 0.85, CHCl3); 1H NMR
(300MHz, CDCl3): d 6.36 (s, 0.7H, olefinic), 6.32 (s, 0.3H,
olefinic), 6.01 (s, 0.7H, olefinic), 5.94 (s, 0.3H, olefinic),
4.58 (br s, 0.7H, allylic), 4.39 (br s, 0.3H, allylic), 4.24–4.20
(m, 2H, CH2), 4.05–3.98 (m, 2H, –O–CH2–), 3.80–3.70 (m,
1H, –O–CH–), 3.30–2.98 (m, 2H, epoxide), 2.66 (d, 0.3H,
J = 4.5Hz, OH), 2.43 (d, 0.7H, J = 6.04Hz, OH), 1.38–
1.25 (m, 9H, 3 · CH3); HPLC (column: chiral OD, 10%
isopropanol in n-hexane, flow rate: 1mL/min,
2. Navak, S. K.; Thijs, L.; Zwanenburg, B. Tetrahedron Lett.
1999, 40, 981–984.
3. (a) Behrens, C. H.; Sharpless, K. B. Aldrichim. Acta 1983,
16, 67–79; (b) Katsuki, T.; Martin, V. S. Asymmetric
epoxidation of allylic alcohols. In Org. React.; Paquette,
L. A., Ed.; John Wiley & Sons: New York, 1996; Vol. 48,
pp 1–299.