LETTER
Chiral Sulfoxide Ligands in Catalytic Asymmetric Cyanohydrin Synthesis
239
between (S )-7 and 10–12 would suggest that this is not
(4) Recent examples include: (a) Gama, A.; Flores-López, L.
S
Z.; Aguirre, G.; Parra-Hake, M.; Somanathan, R.; Walsh, P.
J. Tetrahedron: Asymmetry 2002, 13, 149. (b) Liang, S.;
Bu, X. R. J. Org. Chem. 2002, 67, 2702. (c)Aspinall, H. C.;
Greeves, N. J. Orgmet. Chem. 2002, 647, 151. (d)Wang, Z.
G.; Fetterly, B.; Verkade, J. G. J. Orgmet. Chem. 2002, 646,
the case. Therefore it is evident that the sulfoxide moiety
2
9
plays an integral role in catalysis. Whilst we have evi-
dence that the sulfoxide moiety can participate in the de-
3
0
sired dual activation pathway, it seems unlikely that it is
in this example. The absolute stereochemistry of the ma-
jor cyanohydrin product was the same regardless of the
presence of the Lewis base (Table 1; entry 10 vs. 16). Al-
ternatively, the sulfoxide could be coordinated to the met-
al centre to give a coordinatively saturated titanium
161. (e) Tian, S.-K.; Deng, L. J. Am. Chem. Soc. 2001, 123,
6195. (f) Brunel, J. M.; Legrand, O.; Buono, G.
Tetrahedron: Asymmetry 1999, 10, 1979. (g) Hwang, C. D.;
Hwang, D. R.; Uang, B. J. J. Org. Chem. 1998, 63, 6762.
(
(
h) Abiko, A.; Wang, G.-Q. Tetrahedron 1998, 54, 11405.
i) Zi, G. F.; Yin, C. L. J. Mol. Catal. A: Chem. 1998, 132,
1
complex. H NMR of the titanium complex of the methyl
L1–L4. (j) Mori, M.; Imma, H.; Nakai, T. Tetrahedron Lett.
997, 38, 6229. (k) Iovel, I.; Popelis, Y.; Fleisher, M.;
sulfoxide 6 showed a downfield shift in the methyl singlet
compared to the free ligand consistent with coordination.
The sulfoxide moiety does not displace an iso-propoxide
1
Lukevics, E. Tetrahedron: Asymmetry 1997, 8, 1279.
(5) General review of bifunctional catalysts: (a) Rowlands, G.
J. Tetrahedron 2001, 57, 1865. (b) Recent examples: Casas,
J.; Nájera, C.; Sansano, J. M.; Saá, J. M. Org. Lett. 2002, 4,
2589. (c) Also see: Gröger, H. Chem.–Eur. J. 2001, 7, 5247.
1
unit as H NMR clearly indicates the presence of three iso-
propoxide units within the complex. The sulfoxide could
3
1
then behave as a hemi-labile ligand, forming a vacant
site on the titanium that would allow facile coordination
and activation of the aldehyde. Such an explanation does
not satisfactorily explain the selectivity differences be-
tween the two sulfoxide configurations. Interestingly,
(
d) Examples on the related addition to imines: Liu, B.;
Feng, X.; Chen, F.; Zhang, G.; Cui, X.; Jiang, Y. Synlett
001, 1551. (e) Also see: Corey, E. J.; Wang, Z.
2
Tetrahedron Lett. 1993, 34, 4001.
(6) (a) Shen, Y.; Feng, X.; Li, Y.; Zhang, G.; Jiang, Y. Synlett
6
2002, 793. (b) Shen, Y.; Feng, X.; Zhang, G.; Jiang, Y.
Feng recently reported N-oxide titanium complexes ca-
Synlett 2002, 1353.
talysed the cyanosilylation of ketones. Whilst they pro-
pose a dual activation pathway their complexes can also
undergo internal coordination. It is clear that further study
is required to elucidate the mechanism of the sulfoxide-
mediated process.
(
7) Recent examples and references therein: (a) Masumoto, S.;
Yabu, K.; Kanai, M.; Shibasaki, M. Tetrahedron Lett. 2002,
43, 2919. (b) Kanai, M.; Hamashima, Y.; Takamura, M.;
Shibasaki, M. J. Synth. Org. Chem. Jpn. 2001, 59, 766.
(c) Shibasaki, M.; Kanai, M. Chem. Pharm. Bull. 2001, 49,
5
11.
In conclusion, a novel sulfoxide containing ligand for the
cyanosilylation of aldehydes has been developed. The re-
action is mechanistically interesting as a result of the cru-
cial role played by the Lewis basic sulfoxide in catalyst
activity. Work to modify the chiral scaffold to improve the
enantioselectivity and to extend the use of sulfoxides in
(
(
8) (a) Deng, H.; Isler, M. R.; Snapper, M. L.; Hoveyda, A. H.
Angew. Chem. Int. Ed. 2002, 41, 1009. (b) Mechanistic
studies on the related addition to imines: Josephsohn, N. S.;
Kuntz, K. W.; Snapper, M. L.; Hoveyda, A. H. J. Am. Chem.
Soc. 2001, 123, 11594.
9) (a) Belokon’, Y. N.; Gutnov, A. V.; Moskalenko, M. A.;
Yashkina, L. V.; Lesovoy, D. E.; Ikonnikov, N. S.; Larichev,
V. S.; North, M. Chem. Commun. 2002, 244. (b) Belokon',
Y. N.; Green, B.; Ikonnikov, N. S.; North, M.; Parsons, T.;
Tararov, V. I. Tetrahedron 2001, 57, 771.
3
2
Lewis base promoted reactions is currently underway
and will be reported in due course.
(
10) (a) Pelotier, B.; Anson, M. S.; Campbell, I. B.; Macdonald,
S. J. F.; Priem, G.; Jackson, R. F. W. Synlett 2002, 1055.
(b) Massa, A.; Lattanzi, A.; Siniscalchi, F. R.; Scettri, A.
Tetrahedron: Asymmetry 2001, 12, 2775. (c) Brinksma, J.;
La Crois, R.; Feringa, B. L.; Donnoli, M. I.; Rosini, C.
Tetrahedron Lett. 2001, 42, 4049. (d) Procter, D. J. J. Chem.
Soc., Perkin Trans. 1 2001, 335.
Acknowledgement
The author would like to thank Dr. Peter Hitchcock for X-ray
crystallography.
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