inactive, the chromium(III) complex 1 did catalyze the
reaction to a limited extent. A turnover frequency below 1
h-1 was measured and the ring-opened product 3 was
obtained in 14% ee. While these results indicated that Cr(III)
might be a competent metal ion for aziridine ring opening,
we suspected that the steric requirements of the coordinated
aziridine might be the cause for diminished enantioselectivity
and reactivity with the salen complexes relative to that seen
with epoxides and the same catalyst (Figure 1). Following
Table 1. Asymmetric Ring Opening of N-2,4-Dinitrobenzyl
Cyclopentene Imine (2) Catalyzed by Cr(III) Complexes of
Ligands 4-10a
ligand
4
5
6
7
8
9
10
70
100
ee (%)b
convn (%)c
4
30
7
50
24
60
66
100
64
100
69
100
a Reactions were carried out at room temperature in acetone with 5 mol
% of catalyst. b Enantiomeric excesses were determined by HPLC analysis
of crude reaction mixtures. c Reaction time was 24 h for 4-6 and 3 h for
7-10.
higher enantioselectivity with more sterically demanding
3-substituents.7 In this manner, ligand 10 was identified as
the most effective of those evaluated, and it was selected
for further study.
The identity of the aziridine N-substituent was found to
play an important role in the enantioselective ring opening.
Sulfonyl-protected aziridines proved unreactive with any of
the Cr Schiff base catalysts examined, while high conversions
but low enantioselectivities were observed with amide and
carbamate derivatives. N-Alkyl-substituted aziridines proved
to be the most effective substrates by a wide margin, with
those bearing the highly electron-deficient 2,4-dinitrobenzyl
group giving the best results.8
Figure 1. Schematic illustrating the possible advantage of tridentate
ligands for the activation of aziridines.
this rationale, we evaluated chromium(III) complexes of
tridentate ligands 4-10, with the hope that a less sterically
hindered coordination environment at the catalyst might lead
to improved results (Figure 2).
Solvent was found to have an important effect on the
reaction rate. In what might be considered an unexpected
result for a Lewis acid-catalyzed process,7 reactions carried
out in acetone proceeded with the fastest rates, with reactions
reaching complexion within 3 h at room temperature in the
presence of 5 mol % of 10. In contrast, use of solvents such
as THF, CH2Cl2, and CH3CN led to 27%, 83%, and 63%
conversion, respectively, under the same conditions. On the
other hand, product ee’s were almost invariant in these
different solvents.
The reactivity of the catalyst could be enhanced further
by counterion methatesis to generate the corresponding azide
complex.9 Treatment of the complex derived from ligand 10
and CrCl3 with TMSN3 afforded a catalyst that displayed
reasonable reactivity even at reduced temperatures. This
allowed substantially higher enantioselectivities to be ob-
tained in the ring opening of 2 (74% ee at 20 °C, 87% ee at
-30 °C). Using the optimized catalyst and reaction condi-
Figure 2. Ligands 4-10.
Four different chiral amino alcohols were condensed with
di-tert-butylsalicylaldehyde to provide ligands 4-7. Of these,
the aminoindanol-derived ligand (7) proved substantially
more reactive and enantioselective in the model reaction
(Table 1).6 Variation of the substituents of the salicylidene
aromatic group revealed a subtle-yet-clear trend toward
(7) For a similar trend in asymmetric hetero-Diels-Alder reactions,
see: Dossetter, A. G.; Jamison, T. F.; Jacobsen, E. N. Angew. Chem. Intl.
Ed. Engl.1999, 38, 2398.
(8) Osborn, H. M. I.; Sweeney, J. Tetrahedron: Asymmetry 1997, 11,
1693.
(9) Procedure for preparation of catalyst (1S,2R)-10‚CrN3: In a
flame-dried Schlenk flask under a nitrogen atmosphere, (1S,2R)-ligand 10
(763 mg, 1.70 mmol) was disolved in dry THF (30 mL). 2,6-Lutidine (0.79
mL, 6.81 mmol, freshly distilled from CaH2) was added to the flask,
followed by chromium(III) chloride tetrahydrofuran complex (1:3, 97%)
(636 mg, 1.70 mmol). The resulting dark brown solution was stirred under
nitrogen for 12 h and then diluted with tert-butylmethyl ether (200 mL)
and washed with NH4Cl and brine. The organic portion was dried over
Na2SO4 and then concentrated under reduced pressure. The dark brown
air-stable solid thus obtained was treated with TMSN3 (2.25 mL, 17 mmol)
and was stirred under a nitrogen atmosphere overnight at room temperature.
Volatile materials were removed in vacuo. Flash column chromatography
(13-20% acetone in hexane) afforded 459 mg (50% yield) of the complex
as an air-stable brown solid.
(5) (a) Martinez, L. E.; Leighton, J. L.; Carsten, D. H.; Jacobsen, E. N.
J. Am. Chem. Soc. 1995, 117, 5897. (b) Larrow, J. F.; Schaus, S. E.;
Jacobsen, E. N. J. Am. Chem. Soc. 1996, 118, 7420. (c) Schaus, S. E.;
Larrow, J. F.; Jacobsen, E. N. J. Org. Chem. 1997, 62, 4197.
(6) General Procedure for Aziridine Ring-Opening Reaction: To a
stirred solution of tridentate Cr(III) catalyst (5-10 mol %) in 1 mL of dry
solvent was added the aziridine (0.50 mmol) under a nitrogen atmosphere
at room temperature. After 15 min, the reaction temperature was stabilized
as indicated (room temperature or -30 °C) and TMSN3 (1.05 equiv) was
added via syringe. The solution was stirred for the appropriate reaction
time. Finally, the reaction mixture was concentrated in vacuo and isolation
of the pure ring-opened product was accomplished by flash column
chromatography on silica gel.
1612
Org. Lett., Vol. 1, No. 10, 1999
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