Page 7 - Chiral N,N-Dioxides: New Ligands and Organocatalysts for Catalytic Asymmetric Reactions

Chiral N,N -Dioxides Liu et al.
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SCHEME 9. Asymmetric Synthesis of R-Hydroxyoxindole Derivatives SCHEME 11. Asymmetric Hydroxymethylation Reaction

SCHEME 10. Asymmetric Amination Reactions of 2-Oxindole
Derivatives

SCHEME 12. Asymmetric Synthesis of 1,3-Bis(hydroxymethyl)-2-oxi-
ndole Derivatives

azodicarboxylatesandhydroxyaminationusingnitrosoarenes 27
to generate 3-amino-2-oxindole derivatives (Scheme 10).
By exploiting the water-tolerant nature of the scandium
complexes, Kobayashi's group developed an asymmetric
hydroxymethylation reaction between aqueous HCHO and
silicon enolate in water. 28 Both L7Sc(DS) 3 in the presence
0 afford a variety of transformations. Asymmetric aldol reac-
of Triton X-705 and N,N -dioxide L1eSc[O 3 S(CH 2 ) 10 CH 3 ] 3
with CH 3 (CH 2 ) 10 SO 3 Na were able to afford the desired tion of R-diazoacetate and R-ketoesters using the L2fSc-
products with excellent results, and the loading of the latter (OTf) 3 complex was realized to yield tertiary alcohols with
catalyst could be reduced to 12 mol % without sacrificing the reservation of the diazo group (Scheme 13). However,
the reaction efficiency (Scheme 11). when the catalyst was employed in the reaction between
It was found that the L3fNd(OTf) 3 complex was water- aldehydes and R-alkyl-R-diazoacetates, the Roskamp reac-
tolerant in the enantioselective hydroxymethylation reaction tion occurred to produce R-alkyl-β-ketoesters through the
of unprotected 3-substituted-2-oxindoles and formalin. 29 An addition of R-diazoacetate with concomitant 1,2-H-migra-
unexpectedtandemC-andN-additionprocesswasfoundtogive tion and extrusion of diazo (Scheme 13). There are relatively
1,3-bis(hydroxymethyl)-2-oxindole derivatives (Scheme 12). few reports of the catalytic asymmetric Roskamp reaction,
This method reduces the synthetic process to enantioen- due to the difficultly controlling the chemoselectivity and
riched linchpins such as physostigmine and coerulescine. racemization of R-alkyl-β-ketoesters. These issues were ad-
0
Nd(OTf) 3 and the ligand could be recovered and reused with dressed, for the first time, by using the highly efficient N,N -
loss of neither activity nor enantioselectivity. dioxide L3fSc(OTf) 3 catalyst. 30 The catalyst loading could
Roskamp Reaction. R-Diazoesters can function as nu- be reduced to 0.05 mol %, which allowed for convenient
cleophiles, and the decomposition of diazo functionality can separation of the catalyst and the product by flash filtration

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