A R T I C L E S
Lu et al.
Scheme 2
control of the cis/trans selectivity of the aziridines could be
achieved and 20 mol % of the chiral sulfide is required. A third
approach involves the activation of an imine by a chiral Lewis
or Bronsted acid toward reaction with a carbenoid. It is this
latter approach that has been the focus of this laboratory over
the past few years.7
While it has been known for some time that Lewis acids can
effect the formation of aziridines from imines and diazo
compounds, it was not until the work of Brookhart and
Templeton and co-workers8a and later by Jorgensen and co-
workers8b,c that the generality of this process was appreciated.
With the information in these reports, it was found that catalysts
derived from triphenylborate and either vaulted binaphthol
(VANOL) or vaulted biphenanthrol (VAPOL) were effective
in catalyzing the formation of cis-aziridine-2-carboxylates from
N-benzhydrylimines and ethyl diazoacetate (Scheme 2).7b This
asymmetric aziridination reaction (AZ reaction) proved to be
general for imines derived from aromatic and aliphatic
aldehydes giving the aziridine 7 with high cis/trans ratios in
good to high yields with excellent enantioselective
induction. A very surprising aspect to this reaction is that the
VANOL- and VAPOL-derived catalysts were essentially equally
effective in providing asymmetric induction for each imine
examined. This is in contrast to other reactions where either
the VANOL- or VAPOL-derived catalyst was more effective,
Scheme 3
(4) For reports of catalytic asymmetric aziridinations that have appeared after
2003, see (a) Suga, H.; Kakehi, A.; Ito, S.; Ibata, T.; Fudo, T.; Watanabe,
Y.; Kinoshita, Y. Bull. Chem. Soc. Jpn. 2003, 76, 189. (b) Omura, K.;
Murakami, M.; Uchida, T.; Irie, R.; Katsuki, T. Chem. Lett. 2003, 32, 354.
(c) Chanada, B. M.; Vyas, R.; Landge, S. S. J. Mol. Catal. A: Chem. 2004,
223, 57. (d) Liang, J.-L.; Yuan, S.-X.; Chan, P. W. H.; Che, C.-M.
Tetrahedron Lett. 2003, 44, 5917. (e) Taylor, S.; Gullick, J.; McMorn, P.;
Bethell, D.; Page, P. C. B.; Hancock, F. E.; King, F.; Hutching, G. J. Top.
Catal. 2003, 24, 43. (f) Taylor, S.; Gullick, J.; Galea, N.; McMorn, P.;
Bethell, D.; Page, P. C. B.; Hancock, F. E.; King, F.; Willock, D. J.;
Hutching, G. J. Top. Catal. 2003, 25, 81. (g) Fraile, J. M.; Garcia, J. I.;
Herrerials, C. I.; Mayoral, J. A.; Harmer, M. A. J. Catal. 2004, 221, 532.
(h) Aggarwal, V. K.; Vasse, J-L. Org. Lett. 2003, 5, 3987. (i) Solladie-
Cavallo, A.; Roje, M.; Welter, R.; Sunjic, V. J. Org. Chem. 2004, 69, 1409.
(j) Li, J.; Liang, J.-L., Chan, P. W. H.; Che, C.-M. Tetrahedron Lett. 2004,
45, 2685. (k) Fruit, C.; Muller, P. Tetrahedron: Asymmetry 2004, 15, 1019.
(l) Fraile, J. M.; Garcia, J. I.; Lafuente, G.; Mayoral, J. A.; Salvatella, L.
ARKIVOC 2004, iV, 67. (m) Xu, J.; Ma, L.; Jiao, P. Chem. Commun. 2004,
1616. (n) Saniere, L.; Leman, L.; Bourguignon, J.-J.; Dauban, P.; Dodd,
R. H. Tetrahedron 2004, 60, 5889. (o) Fioravanti, S.; Mascia, M. G.;
Pellacani, L.; Tardella, P. A. Tetrahedron 2004, 60, 8073. (p) Omura, K.;
Uchida, T.; Irie, R.; Katsuki, T. Chem. Commun. 2004, 2060. (q) Gullick,
J.; Ryan, D.; McMorn, P.; Bethell, D.; King, F.; Hancock, F.; Hutching,
G. New J. Chem. 2004, 28, 1470. (r) Ryan, D.; McMorn, P.; Bethell, D.;
Hutching, G. Org. Biomol. Chem. 2004, 2, 3566. (s) Redlich M.; Hossain,
M. M. Tetrahedron Lett. 2004, 45, 8987. (t) Murugan, E.; Siva, A. Synthesis
2005, 12, 2022. (u) Ma, L.; Du, D.-M.; Xu, J. J. Org. Chem. 2005, 70,
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and in no other case was such a nearly identical profile
observed.9,10
Many of the optically active benzhydrylaziridines 7 that we
have considered for various synthetic applications would require
removal of the N-benzhydryl group to form N-H-aziridine 13
(Scheme 3) and reprotection with an electron-withdrawing group
on the nitrogen. Thus, for maximum versatility, there would be
a need for deprotection methods that would allow for the clean
conversion of benzhydrylaziridines 7 to N-H-aziridines 13.
Alternatively, a better solution would be to perform the reaction
with an imine already bearing an electron-withdrawing group
on the nitrogen. However, it was found that the benzhydryl
group was essential for achieving high asymmetric inductions
in these reactions. Efforts to replace the benzhydryl on the imine
with a benzyl group, a trityl group, or to employ diphenylphos-
phinoylimines or diphenylhydrazones led to either low reactivity
or low asymmetric induction.
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The most common method for deprotection of N-benzhydry-
lamines is treatment with acid, and this is also viable for certain
N-benzhydrylaziridines.11 However, aryl-substituted N-benzhy-
(9) The VANOL and VAPOL ligands are now commercially available from
Sigma-Aldrich Corp. and Strem Chemicals, Inc.
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7186 J. AM. CHEM. SOC. VOL. 129, NO. 22, 2007