Page 9 - Chiral N,N-Dioxides: New Ligands and Organocatalysts for Catalytic Asymmetric Reactions

Chiral N,N -Dioxides Liu et al.
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SCHEME 16. Asymmetric Michael Reaction of 4-Substititued
5-Pyrazolones

FIGURE 5. Asymmetric conjugate additions of nitroalkanes.

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the reaction without extra solvent, whereas N,N -dioxide
Sc(OTf) 3 only produced trace amounts of products.
Central metal promoted reversal of enantioselectivity in
the asymmetric Michael addition between 4-substititued-5-
pyrazolones and 1,4-dicarbonylbut-2-enes was discovered.
Using L2h as the ligand, both the Sc(OTf) 3 complex and the
Y(OTf) 3 complex were able to provide the products but with
reversed enantioselectivity (Scheme 16). 35 The influence of
the solvent was carefully studied, as it may be a key factor in
the stereoswitching.
Following C-nucleophiles in the conjugate additions, we
examined the sulfa-Michael reaction between thioglycolate

FIGURE 6. Asymmetric conjugate additions of malonates. and chalcones. Again, the screening of catalysts highlights
the influence of the nature of the ligand on the activity and
enones including (E)-4-oxo-4-arylbutenoates, chalcones, enantioselectivity of the reaction. Ligands bearing 2,6-diiso-
and cinnamones (Figure 5). 33 Benzylamine-derived L3a propylphenylamine were crucial to the enantioselectivity,
and L1fLa(OTf) 3 conferred extremely high inducement (up
Sc(OTf) 3 showed superior performance versus L3fSc(OTf) 3
in the Michael reaction of malonates or R-chloromalonate to 99% ee) at 1 mol % or even 0.01 mol % catalyst loading. 36
with a wide range of chalcone derivatives or (E)-4-oxo-4- The reaction also exhibited an intriguing asymmetric ampli-
arylbutenoates (Figure 6). 34 In the case of β,γ-unsaturated ficationphenomenoninwhichhighenantioselectivity(98%ee)
R-ketoesters and malonates, L2fY(OTf) 3 instead promoted was achieved by using La(OTf) 3 and 2% ee ligand L1f at

FIGURE 7. Asymmetric sulfa-Michael reaction.

582 ’ ACCOUNTS OF CHEMICAL RESEARCH ’ 574–587 ’ 2011 ’ Vol. 44, No. 8