Page 6 - Chiral N,N-Dioxides: New Ligands and Organocatalysts for Catalytic Asymmetric Reactions

Chiral N,N -Dioxides Liu et al.
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SCHEME 5. Asymmetric Synthesis of 2,3,5-Trisubstituted SCHEME 7. Asymmetric Synthesis of Tetrahydroquinolines
Dihydropyrones

SCHEME 8. Asymmetric DA and IEDDA Reactions

SCHEME 6. Asymmetric Synthesis of Dihydropyridinones

in aqueous media, was most suitable for the asymmetric the oxazolinescandium complex provide an insight into
cycloaddition of N-arylimines. Moderate to good enantios- the potential of the synthetic avenues of N,N -dioxides.
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electivities were achieved at a 2:1 molar ratio of L1f to Aldol Type Reaction. The asymmetric aldol reaction
Sc(OTf) 3 (Scheme6).Astrongpositivenonlinearrelationship 23 remains the focus of extensive studies, and the develop-
between the enantiomeric excess of the product and L1f ment of the useful nucleophiles for such reactions is of great
was observed which might be due to the reservoir effect. importance, especially for the construction of quaternary
N-Arylimines are also able to serve as dienes in the stereogenic centers. Biologically active oxindole-containing
inverse electron-demand aza-DielsAlder reaction (IEDDA),
compounds could be conventionally produced from oxi-
using electron-rich alkenes as dienophiles to produce tetra-
ndoles or isatins. We first focused our attention on the aldol
hydroquinolines. Previous efforts using cyclopentadiene as 26
reaction of 3-substituted oxindoles. Neither Sc(OTf) 3 nor N,
the dienophile failed to produce the mutual benefits of high
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N -dioxide by itself could initiate the reaction between
yield and enantioselectivity. Lewis acids such as La(OTf) 3 ,
3-methyl-2-oxindole and glyoxal derivatives. However, it
Y(OTf) 3 , and Yb(OTf) 3 produced only trace amounts of the
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wasfound that,ina ligand-accelerated process,N,N -dioxide
product. Catalyst L3fSc(OTf) 3 , derived from L-ramipril acid,
Sc(OTf) 3 complex could promote the reaction efficiently. The
exhibited excellent stereofacial discrimination in the reac-
yield and stereoselectivity were affected by the amide
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tion (Scheme 7). Chiral cyclopenta[3,2,c]quinolines were
moiety of the ligand. 2,6-Diisopropylbenzenamine-derived
obtained from various aldehydes in a one-pot synthesis. The
ligands exhibited better yields than others, with L2f pro-
products may undergo transformations to potentially phar-
ducing the best results. The addition of 3 Å molecular
maceutically active tetrahydroquinoline derivatives.
sieves shortened the reaction time. Various glyoxals or
The L2fCu(OTf) 2 complex was used in asymmetric cy-
trifluoropyruvates and 3-substituted-2-oxindoles could be
cloadditions of β,γ-unsaturated R-ketoesters with cyclopenta-
diene as diene or dienophile, respectively (Scheme 8). 25 used toproduce3-(R-hydroxy-β-carbonyl)oxindoleswithqua-
Brideged bicyclic compounds were the main product of the ternary stereocenters (Scheme 9). Although the ratio of ligand
DielsAlder (DA) process at room temperature, whereas to Sc(OTf) 3 was 1:1, a (þ)-NLE was observed for both diaste-
ring-fused pyran derivatives were the dominant product of reomers, which was a consequence of the formation of
the IEDDA process at 20 °C. The improved chemoselec- oligomeric species. 23 The same catalyst could also success-
tivity and milder reaction conditions compared with those of fully be employed in the enantioselective R-amination using
Vol. 44, No. 8 ’ 2011 ’ 574–587 ’ ACCOUNTS OF CHEMICAL RESEARCH ’ 579