2, 3, 5, 16, 22) although this is not always so (entries 17,
21).
These results have implications for the mode of stereo-
selection in epoxidation using metal-salen complexes. In the
manganese series, and within the side-on approach model,
essentially all possible alkene trajectories to the oxo-complex
have previously been used as a basis for explaining
enantioselectivity.2a Thus Jacobsen,2b assuming a flat salen
geometry, considers alkene approach to the metal-oxo bond
along either of pathways a or b (Figure 1). Which one occurs
Introduction of a chloro substituent in the Y-position
causes either no change or a reduction in selectivity (entries
1/3, 2/6, 4/9, 11/12). Similarly, a halogen at the X-position
is either irrelevant or detrimental (compare entries 1/4, 2/7,
3/9, 5/10, 8/11, 13/14, 1/15, 16/17). This was also observed
in our previous comparison of tert-butyl substitution at X
and Z.3a,b Substitution at the W-position has mostly a positive
influence in the absence of a Z-substituent (compare 1/5,
4/10). However, W- and Z-substitution are not cooperative,
the ee being a composite of the two contributing mono-
substituents (compare entries 2/5/8, 7/10/11, 20/21). In the
presence of L ) Ph3PO, the larger halogen substituents have
an increasingly negative effect on ee (compare entries 2/13/
16, 7/14/17/18), although this is less clear with no L.
Introduction of groups electron donating by resonance
appears to be very detrimental (entries 19 and 22), but there
is not enough data for conclusive analysis.
Figure 1. Approach trajectories.
The effect of the donor ligands L is in line with our
previous findings.3b Triphenylphosphine oxide is the best-
behaved ligand, being most consistent in raising the ee (up
to 20%). DMF and DMSO usually have similar effects
although the elevation is less. However 4-phenylpyridine
N-oxide is more capricious, lowering ee dramatically (entries
7, 8, 11, 17) or giving the highest for some complexes
(entries 4, 5, 14, 15).
depends on the nature of the imine bridge and on the presence
or absence of large groups at the X-position, pathway b
applying to the tetra-tert-butyl catalyst (Jacobsen’s Catalyst).
Early on in the development of this area, Katsuki16 proposed
approach c to explain a number of results that were not
adequately accommodated by pathway b. He was also able
to retain this pathway c when he proposed10 the nonplanar
geometry of the complex. It is more difficult to retain
pathway b in a nonplanar geometry because the most
commonly proposed deviation from planarity is the stepped
conformation, Figure 2 and in it pathway b suffers from some
There is also interplay between the salen substituents and
L. The last column in Table 1 shows the increase in the free
energy difference between the transition states leading to the
enantiomers (∆∆∆G‡) on addition of triphenylphosphine
oxide. We have previously2a,3d noted, for ligands with a
Z-only substituent, that the more enantioselective the system
is without L, the less the benefit derived on addition of L.
We termed this a “ceiling effect”, and it is also apparent
here (entries 2/13/16/20, counter example 22). We speculated3d
that increased stereoselection in the system is due to the
attainment of a conformation which is promoted both by
Z-substitution and by the donor ligand L, with the latter less
effective. In complexes with suitable Z, the conformation
without L reaches an optimum, and the effect of L is thus
minimal. Finally a loose generalization about W-Z versus
L can also be made from Table 1: addition of triphenylphos-
phine oxide appears to be most beneficial to stereoselection
when X and Z or both are substituted (entries 2/4/7/13/14/
15/16/1718, counter examples 20/22) while the least benefit
accrues when W and Y are substituted (entries 3/5/19) with
mixed X-Z/W-Y cases intermediate or worse (entries 6/8/
9/10/11/12).
(9) Norrby, P. O.; Linde, C.; Åkermark, B. J. Am. Chem. Soc. 1995,
117, 7, 11035-11036;
(10) Hamada, T.; Fukuda, T.; Imanishi, H.; Katsuki, T. Tetrahedron 1996,
52, 515-530; Hashihayata, T.; Ito, Y.; Katsuki, T. Synlett 1996, 1079;
Hashihayata, T.; Ito, Y.; Katsuki, T. Tetrahedron 1997, 53, 9541-9552;
Miura, K.; Katsuki, T. Synlett 1999, 783-785.
(11) Houk, K. N.; DeMello, N. C.; Condroski, K.; Fennen, J.; Kasuga,
T. In Electronic Conference on Heterocyclic Chemistry, ECHET96; Rzepa,
H. S., Snyder, J. P., Leach, C., Eds.; Royal Society of Chemistry: London,
(12) (a) Plattner, D. A.; Feichtinger, D.; El-Bahraoui, J.; Wiest, O. Int.
J. Mass Spectrom. 2000, 195/196, 351-362; (b) El-Bahraoui, J.; Wiest,
O.; Feichtinger, D.; Plattner, D. A. Angew. Chem., Int. Ed. 2001, 40, 2073-
2076.
(13) In addition to the known importance of the Z-position (ref 2),
Jacobsen and co-workers have studied comprehensively substitution at the
X position: Palucki, M.; Finney, N. S.; Pospisil, P. J.; Gu¨ler, M. L.; Ishida,
T.; Jacobsen, E. N. J. Am. Chem. Soc. 1998, 120, 948-954 and references
therein.
(14) Experimental procedure: CAUTION! Cr(V)dO species are known
carcinogens, all complexes were generated in situ. Chromium(III)-salen
complex (40-60 mg, 1 equiv) in acetonitrile (3 mL) was treated with
iodosylbenzene (1.2 equiv), the resulting green solution filtered after 10
m, treated with donor ligand L (1 equiv), cooled to 0 °C, treated with E-â-
methylstyrene (9-12 µL, 1 equiv), and left until an orange color persisted.
After evaporation and short path chromatography (alumina, Et2O), analysis
was by csp GLC on a Supelco R-cyclodextrin capillary column with
n-decane as internal standard. Product configuration was determined and
precursor chromium(III)-salen complexes prepared as described previously
(ref 3d).
(15) Samsel, E. G.; Srinivasan, K.; Kochi, J. K. J. Am. Chem. Soc. 1985,
107, 7606-7617.
(16) Hosoya, N.; Hatakeyama, A.; Yanai, K.; Fujii, H.; Irie, R.; Katsuki,
T. Synlett 1993, 641-645. Hamada, T.; Irie, R.; Katsuki, T. Synlett 1994,
479-481.
(8) Previously, Norrby, Linde, and Åkermark9 had proposed a nonplanar
salen ligand in their putative oxametallocylic intermediate for epoxidation
in the manganese series. Subsequently, both Katsuki and co-workers10 and
Houk and co-workers11 adduced evidence for nonplanar manganese salens;
the latter on the basis of a reexamination of crystal structures of manganese-
(III)-salen complexes in the Cambridge Structural Database. The former
also called attention to nonplanar crystal structure data to explain the striking
effects of certain chiral ligands on epoxidations using achiral manganese-
salen complexes. Recently, high level calculations by Plattner, Wiest, and
co-workers12 on these systems have revealed a great amount of detail about
the exact nature of the distortions from planarity.
Org. Lett., Vol. 3, No. 22, 2001
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