Page 5 - Chiral N,N-Dioxides: New Ligands and Organocatalysts for Catalytic Asymmetric Reactions

Chiral N,N -Dioxides Liu et al.
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SCHEME 3. Other N,N -Dioxide Catalyzed Strecker Reactions
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Cycloaddition Reaction. The catalytic asymmetric [4 þ 2]
SCHEME 4. R-Chlorination of Cyclic β-Ketoesters
cycloaddition reaction is effective for the construction of six-
membered ring compounds. Chiral dihydropyranones, dihy-
dropyridinones, and tetrahydroquinolines were obtained
using chiral N,N -dioxidemetal complexes.
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Chiral 2,5-disubstituted dihydropyrones have been pre-
pared via asymmetric hetero-DielsAlder (HDA) reaction of
Danishefsky's diene derivatives using a Schiff baseCr(III)
complex or BINOLTi(IV) complex. However, control of the
stereochemistry of the reaction of 2,5-dimethyl substituted
Danishefsky-type diene to produce 2,3,5-trisubstituted dihy-
r-Chlorination of β-Ketoesters. Asymmetric halogena- dropyrone with two chiral centers is more difficult. We
tion is a useful strategy for producing halogen-containing attempted to realize this reaction by the use of chiral
chiral compounds. The N,N -dioxide L2f was effective for the N,N -dioxide as a ligand. 21 Indium(III), an element that is
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asymmetric R-chlorination of cyclic β-ketoesters with about three times as abundant as silver, was found to be
N-chlorosuccinimide (NCS). It represents a departure from amenable to coordination with N,N -dioxide and activating
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the conventional role of N-oxide as an activator for silicon carbonyl groups. The subunits of the N,N -dioxide moiety
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reagents. 19 A series of R-chloro-β-ketoesters were obtained exerted significant effects on both the yield and the stereo-
in 8698% ee. The bifunctional character of the organoca- selectivity of the reaction. Interestingly, aromatic- and ali-
talyst enables simultaneous activation of NCS with amide- phatic-amide-based N,N -dioxides exhibited enantioswitching
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NH and of the β-ketoester with the N-oxide moiety as a and the former produced better results. The stable catalyst
hydrogen acceptor (Scheme 4). L2fIn(OTf) 3 mixed with 4 Å molecular sieves showed
excellent activity and chiral control in the formation of
N,N -Dioxides as Chiral Ligands in Metal 3,5-dimethyldihydropyranones from a variety of aromatic, ali-
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Complexes Catalysis phatic, and cyclic aldehydes (Scheme 5). Subgram quantities
The utilization of N-heteroaromatic N-oxides in metal com- of propionaldehyde could be used for the transformation to
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plexes can be traced back to the 1970s, but their applica- the triketide. The cycloaddition of 2-methyl-substituted Da-
tion to asymmetric catalysis lay dormant for decades. Chiral nishefsky-type diene also performed well with 8098% ee.
pyridineN-oxidemetal complexes were sporadically Chiral Lewis acids including binaphtholZr(Ot-Bu) 4 ,
used in a negligible number of asymmetric reactions with binaphtholboron, and ferroceneCu(I) were developed
less than satisfactory results, which eclipsed their roles in for the aza-DielsAlder reaction of Danishefsky's diene to
asymmetric transformations. A major breakthrough came in synthesize chiral 2,5-disubstituted dihydropyridinones. We
the form of our study on the N,N -dioxideIn(III) complex have utilized an N,N -dioxidescandium(III) complex to cat-
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catalyzed enantioselective allylation reaction, 20 following alyze the asymmetric cycloaddition of N-arylimines gener-
which the use of N,N -dioxides as versatile ligands in asym- ated from aldehydes and 2-aminophenol. 22 Sc(OTf) 3 , which
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metric reactions was expanded. has the advantages of strong Lewis acidity and stability even

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