aldehyde, coordinated cis to the allyl19 via a hexacoordinated
silicon,20,21 can be considered to be trans-disposed either to
Cl or to N of the other pyridine nucleus.
Scheme 3
Molecular modeling suggests that the preferred stereo-
structure of the transition state will be dictated by the twist
about the 2,2′-bipy axis in 8, which in turn must be controlled
by the configuration of the terpene moieties. Since the
atropoisomers of the noncoordinated (+)-8 cannot be iso-
lated, we envisioned that this issue could be addressed by
the corresponding 3,3′-dimethyl derivative, where the rotation
barrier should be higher. To this end, dimethyl-PINDY (+)-6
was synthesized using a protocol analogous to that developed
for PINDY14 (see Supporting Information). Its oxidation with
MCPBA (unoptimized) afforded a ∼1:2 mixture of atropo-
isomeric monoxides (+)-9 and (-)-10 that were separated
by chromatography.22
observed sense of the asymmetric induction. The present
catalyst is characterized by its heterobidentate nature (with
one strong and one weak donor), which contrasts with the
homobidentate and monodentate catalysts reported by other
groups. The mechanistic analysis suggests that, while one
ligating group (N-O) of (+)-8 activates the allyl silane, the
other N stabilizes the intermediate by chelation, thereby
reducing the number of diastereoisomeric transition states,
which results in high enantioselectivity. Further applications
of PINDOX-type catalysts in related reactions8,25 are being
investigated.
On the allylation reaction 1a + 2 f 3a, (+)-9 induced
the formation of the same enantiomer of 3a as did (+)-8
but with higher enantioselectivity (98% ee; entry 19); 1f
reacted similarly (entry 20). By contrast, (-)-10 gave the
opposite enantiomer with slightly lower enantioselectivity
(entry 21). Hence, as expected, the asymmetric induction is
mainly controlled by the configuration at the 2,2′-bipy bond,
which must be identical for (+)-8 and (+)-9. The configu-
ration of (-)-10 was found to be (S) by X-ray crystal-
lography,23 so that (+)-9 must have (R) configuration.
Molecular modeling shows that this architecture will favor
the intermediate A (Scheme 3), in the case of both 9 and 8.
Interestingly, modeling and preliminary crystallographic data
found (+)-824 to be (S)-configured at the chiral axis [rather
than (R)]. Hence, if reproduced in the solution, the molecule
would have to flip to the (R)-configuration upon the
coordination of the reactants (prior to the reaction).
Acknowledgment. We thank AstraZeneca UK Ltd for a
studentship to D.P., the University of Rome “La Sapienza”
for support to M.O., and the University of Glasgow for
additional support. We also thank Dr. Sˇ. Vyskocˇil for the
crystallization of (-)-10.
Supporting Information Available: Experimental pro-
cedures, analytical and spectral data, crystallographic data,
and copies of the NMR spectra for the key compounds. This
material is available free of charge via the Internet at
In conclusion, new bipyridine N-monoxide (+)-8 has been
synthesized and shown to exercise a high level of enantio-
control in the Sakurai-Hosomi-type reaction. With the aid
of the configurationally fixed pair of atropoisomers (+)-9
and (-)-10, the stereochemistry of the reaction has been
demonstrated to be controlled by the 2,2′-bipy chiral axis
and intermediate A has been proposed to account for the
OL025654M
(22) In solution, the two atropoisomers slowly interconvert at room
temperature, eventually reaching the thermodynamic equilibrium within
about a week. In the solid state, (+)-9 appears to be reasonably stable when
stored in a freezer.
(23) Crystal data for (-)-10: white crystals, space group P212121, a )
7.15070(10) Å, b ) 16.83000(10) Å, c ) 38.17410(10) Å, V ) 4594.11(7)
Å3, Z ) 8, dcalc ) 1.123 g cm-3, µ ) 0.068 mm-1, RF ) 0.0534. Two
molecules are present in the cell, differing from each other, e.g., in the
dihedral angle N(O)-C(2)-C(2′)-N (100.6° and 102.6°, respectively).
(24) Crystal data for (+)-8: white crystals, space group P212121, a )
6.8339(2) Å, b ) 11.0443(5) Å, c ) 26.0682(10) Å, V ) 1967.51(13) Å3,
Z ) 8, dcalcd ) 1.217 g cm-3, µ ) 0.074 mm-1, RF ) 1.021.
(25) Thus, our preliminary experiments showed that the cleavage of
cyclooctene epoxide with SiCl4, catalyzed by (+)-8, afforded the corre-
sponding chlorohydrin of 85% ee, which is the highest enantioselectivity
reported to date. For other examples of this reaction and a recent discussion,
see: (a) Denmark, S. E.; Wunn, T.; Jellerichs, B. G. Angew. Chem., Int.
Ed. 2001, 40, 2255 and references cited therein. For a withdrawal of earlier
claims, see: (b) Buono, G. Angew. Chem., Int. Ed. 2001, 40, 4536.
(19) A cyclic transition has been generally accepted.6,8,13
(20) Hexacoordinated complexes of bidentate pyridine-derived N,N-
monoxides with metals, such as Cu(II) and Co(II), have been reported: (a)
Anderson, R. J.; Hagback, P. H.; Steel, P. J. Inorg. Chim. Acta 1999, 284,
273. (b) Vrbova´, M.; Baran, P.; Bocˇa, R.; Fuess, H.; Svoboda, I.; Linert,
W.; Schubert, U.; Wiede, P. Polyhedron 2000, 19, 2195.
(21) This analysis is consistent with the Denmark model6 but in conflict
with the mechanism proposed by Nakajima for 4,13 where the stereo-
electronic effects were not considered. Note that while 4 and 7 allow the
formation of a seven-membered chelate, 8 should operate via a six-
membered ring.
Org. Lett., Vol. 4, No. 6, 2002
1049
Malkov, Andrei V.
