Page 8 - Chiral N,N-Dioxides: New Ligands and Organocatalysts for Catalytic Asymmetric Reactions

Chiral N,N -Dioxides Liu et al.
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SCHEME 13. Asymmetric Reactions of R-Diazoacetates SCHEME 15. Asymmetric HeteroEne and AzaEne Reactions

SCHEME 14. Asymmetric CarbonylEne Reactions

complex of L2f was developed and used in the ketone-
ene reaction to produce enantioenriched trifluoromethyl-
substituted compounds, due to the abundance and low
toxicity of this type of alkaline earth metal. The reaction
could also be conducted under solvent-free conditions
with extremely high enantioselectivity (Scheme 14). Hetero-
ene reaction between isatins and alkyl enol ethers gave
3-substituted 3-hydroxyoxindoles with up to 99% ee
using L3fMg(OTf) 2 catalyst (Scheme 15). 32 Asymmetric
and simultaneously prevented racemization of the product. synthesis of (R)-convolutamydine A was realized conveni-
A series of R-alkyl-R-diazoesters with aromatic aldehydes ently in 97% ee. The activity of Ni(BF 4 ) 2 L2e derived from
could be used to give the chiral R-alkyl-β-ketoesters chemo- 2-bromobenzenamine was superior to that of L2f from
selectively in 8798% ee. Poor results were obtained for 2,6-isopropylaniline in the aza-ene-type reaction of enam-
aliphatic and R,β-unsaturated aldehydes. ides or enecarbamates. 12 2-Hydroxy-1,4-dicarbonyl com-
Ene and AzaEne Reactions. The ene reaction, which pounds with up to 99% ee were obtained (Scheme 15).
involves the nucleophilic addition of an active allylic CH Conjugate Addition of r,β-Unsaturated Compounds.
bond followed by allylic transposition, can be used to con- Michael addition can be used to introduce functionalized
struct multifunctionalized compounds. Significant effort CC, CN, CO, or CS bonds at the β-position of
has been devoted to the asymmetric ene-type reaction of R,β-unsaturated compounds. The efforts encompass num-
glyoxylate using chiral ligands such as BINOL, salen, bis- bers of variants in the terms of the donor and acceptor. Chiral
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(oxazoline), and diamine derivatives. The N,N -dioxide biquinoline N,N -dioxideSc(OTf) 3 has been used in the
metal complexes catalyzed asymmetric reactions employing Michael addition of β-ketoesters to R,β-unsaturated carbo-
glyoxal, ketones, or isatins as enophiles, and alkenes, en- nyl compounds in 7398% yields and 3884% ee by the
amides or enecarbamates, or alkyl enol ethers as nucleo- Nakajima group. 6
philes; those reactions were undertaken with remarkable The efficacy of N,N -dioxidemetal complexes is also
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results (Scheme 14). γ,δ-Unsaturated R-hydroxy carbonyl demonstrated in asymmetric conjugate additions, using
compounds with 97% to >99% ee were obtained from malonates, nitroalkanes, and the thioglycolate as nucleo-
L2fNi(BF 4 ) 2 catalyzed carbonyl-ene reaction of glyoxal philes. Satisfactory results were achieved using L3fSc(OTf) 3
derivatives and glyoxylate. 31 The chiral magnesium(II) and DMAP as additive in the addition of nitroalkanes to

Vol. 44, No. 8 ’ 2011 ’ 574–587 ’ ACCOUNTS OF CHEMICAL RESEARCH ’ 581