Page 122 - Catalysts for Fine Chemical Synthesis Vol 1 - Robert & Poignant

108 hydrolysis, oxidation and reduction

1
H NMR (200 MHz, CDCl 3 ): d 1.32 (s, 3 H, CH 3 ), 1.5 (s, 3 H, CH 3 ), 1.5±
1.7 (m, 7 H), 2.1±2.2 (m, 1H), 2.58 (d, 1 H, J 17 Hz, CH CN), 2.67 (d, 1 H, J
a
17 Hz, CH CN), 4.1 (brs, 1 H, CHOCMe ).
2
b
13 C NMR (50.3 MHz, CDCl 3 ): d 19.5, 22.6, 25.5, 26.2, 26.8, 28.3, 34.6,
76.0, 77.2, 108.3, 116.9.

7.2.2 CONCLUSION

Osmium-catalysed asymmetric dihydroxylation allowed an efficient transform-
ation of (1-cyclohexenyl)acetonitrile to enantioenriched (1,2-isopropylidene-
dioxy)cyclohexylacetonitrile in good yield (65 %) and high enantiomeric purity
(94.7 % ee). This acetonide can be easily transformed in a few steps to a-ketols
bearing allyl or 3-trimethylsilylpropargyl groups, precursors of neurotoxic alka-
loids histrionicotoxins. [7, 8] This methodology enabling the preparation of sub-
stituted a-ketols is superior to that described in the literature. [8, 9] This method
which involves a chromatographic resolution of diastereomeric ketals presents
several drawbacks such as a low efficiency of the chromatographic separation
(DR f ˆ 0:05) and occurrence of a partial racemization during acid deketaliza-
tion.
Sharpless asymmetric dihydroxylation has been successfully applied to (1-
cyclopentenyl)acetonitrile. Using (DHQ)PHN as a ligand in place of
(DHQ) PHAL,* one of the components of AD-mix-a, (S,S)-(1,2-dihydroxycy-
2
clopentyl)acetonitrile was obtained after two recrystallizations, in 50 % yield
and 90 % ee.

REFERENCES

1. Mintz, M.J., and Walling, C. Org. Synth., 1983, Coll. Vol. V, 183.
2. O'Brien, P., Osborne, S.A., and Parker, D.D. J. Chem. Soc., Perkin Trans. 1, 1998,
2519; O'Brien, P., Osborne, S.A., Parker, and D.D. Tetrahedron Lett., 1998, 39, 4099.
3. O'Brien, P. Angew. Chem. Int. Ed. Engl., 1999, 38, 326.
4. Reddy, K.L., and Sharpless, K.B., J. Am. Chem. Soc., 1998, 120, 1207.
5. For the use of asymmetric dihydroxylation and its modifications in organic synthesis
see: Kolb, H.C., Van Nieuwenhze, M.S. and Sharpless, K.B. Chem. Rev., 1994, 59,
2483±547.
6. Devaux, J.M., Gore Â, J. and Vate Ále, J.M. Tetrahedron: Asymmetry, 1998, 9, 1619±26.
7. Compain, P., Gore Â, J. and Vate Ále, J.M. Tetrahedron Lett., 1995, 36, 4063±4.
8. Compain, P., Gore Â, J. and Vate Ále, J.M. Tetrahedron Lett., 1996, 52, 6647±64.
9. Compain, P., Gore Â, J. and Vate Ále, J.M. Tetrahedron Lett., 1995, 36, 4059±62.

* (DHQ)PHN and (DHQ) 2 PHAL are the respective abbreviations of dihydroquinine 9-phenan-
thryl ether and of dihydroquinidine 1,4-phthalazinediyl diether.