Page 4 - Chiral N ,N -Dioxides: New Ligands and Organocatalysts for Catalytic Asymmetric Reactions
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Chiral N,N -Dioxides Liu et al.
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coordination of the substrate in what is hereafter termed a
proper chiral environment. Additionally, the central metal
can also fine-tune the spatial arrangement of the ligand, as
evidenced by the disparity in bond lengths and bond angles
of the various metal complexes.
Based on the aforementioned considerations, the chiral
N,N -dioxide appears to be a suitable choice as an organo-
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catalyst or as a metal ligand in asymmetric catalysis.
FIGURE 4. Possible catalytic model.
N,N -Dioxides as Chiral Organocatalysts
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A number of groundbreaking studies on chiral N-oxides SCHEME 2. Asymmetric Silylcyanation Reactions
toward asymmetric metal-free transformations have been
reported over the last 10 years. 5,6 Stemming from the
formation of hypervalent silicate intermediates, chiral pyr-
idine-type N-oxides have been extensively used in asym-
metric addition reactions of allylchlorosilane.
Silylcyanation of Aldehydes, Ketones, and Imines. The
cyanation of carbonyl compounds and imines is one of the
most prevalent strategies for producing homochiral cyano-
hydrins and amino nitriles. Trimethylsilylcyanide (TMSCN) is
a potential nucleophile, accelerated by anionic or neutral
Lewis bases. However, few studies have attempted to acti-
vate TMSCN with N-oxides. We explored the potential of
N,N -dioxide amide to catalyze silylcyanation reactions, con-
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sidering that it should facilitate the activation of TMSCN and
the electrophile at the fixed positions defined by the dual
activation centers composed of the Lewis base and hydro-
gen bond.
Systematic variation of the subunits of the amide, amino stereoselectively attacked the substrate, which was acti-
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acid, and linker of the N,N -dioxides showed that optimal vated by the hydrogen bond of a nearby amide. In these
silylcyanation of aldehydes was achieved with the L-proline- cases, aliphatic-amine-derived N,N -dioxides achieved better
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based N,N -dioxide L1a (Scheme 2). 13 N,N -Dioxide L1b enantioselectivities owing to the steric hindrance effect of
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was most effective in the asymmetric silylcyanation of the amide subunit. Contemporaneously, a mono N-oxide
R,R-dialkoxy ketones. Interestingly, L1b could be prepared amide was developed by Hoveyda et al., which was em-
in situ from m-chloroperoxybenzoic acid (m-CPBA) and the ployed in the organocatalytic allylation of aldehydes. 16 This
precursor, bisamide L4a. 14 A similar methodology was represents the only other example of the use of an amine
successfully employed in the asymmetric Strecker reaction N-oxide in asymmetric reactions, so far.
of phosphinoyl ketimines with L-piperidinamide L4b and In order to improve the stereoselectivity of the asymmetric
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m-CPBA. 15 Chiral N,N -dioxide was quantitatively recovered reactions, we also designed other types of chiral N,N -dioxides
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and was able to be reused at least five times without loss of (Scheme 3). The connection of amides via (1S,2S)-1,2-
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efficiency. diphenylethane-1,2-diamine produced the N,N -dioxide L5
Comparative experiments using a mono N-oxide amide which exhibited improved performance in the three-com-
or bisamide yielded poor results. 14,15 A possible bifunctional ponent Strecker reaction. 17 A concentration of 2 mol % of
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catalytic model of N,N -dioxide organocatalysis is shown in catalyst L6, which incorporates the BINOL structure, effi-
Figure 4. The hypervalent silicon intermediate generated ciently catalyzed the Strecker reaction of various aryl and
from the bidentate N,N -dioxide which enhanced both alkyl N-tosyl ketimines in 9099% enantiometric excess
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the nucleophilicity of the cyano group and the rigidity (ee), 18 indicating that organocatalysts with more rigid back-
of the reaction environment. The cyano group therefore bones could enhance the stereoselectivity of the reaction.
Vol. 44, No. 8 ’ 2011 ’ 574–587 ’ ACCOUNTS OF CHEMICAL RESEARCH ’ 577