Grignard Addition to Imines Derived from Isatine: A Method for the Asymmetric Synthesis of Quaternary 3-Aminooxindoles

Abstract

Addition of Grignard reagents to chiral imines derived from isatine afforded chiral, optically enriched 3-substituted 3-aminooxindoles in satisfactory yields and diastereoisomeric ratios. A general protocol is described for the addition of alkyl, alkenyl, and aryl Grignard reagents. In one case, the absolute configuration at C3 was determined and the selective N-deprotection was described, enabling further synthetic transformations of the reaction product.

Catalytic Asymmetric Synthesis of Oxindoles Bearing a Tetrasubstituted Stereocenter at the C‐3 Position

“…The use of a lower amount of chiral catalyst (1 mol% or less) is for sure practical and attractive; iii) to develop new reactions. For example, although the catalytic asymmetric addition of nucleophiles to ketimines has been developed very fast,5g–i ketimines derived from isatins have not been integrated in these transformations;62 iv) to achieve protecting‐group‐free synthesis. While most of the current methods employ starting materials with N ‐protecting groups, the oxindole subunit in most of the natural products and pharmaceuticals is without protecting groups.…”

Stereoselective Synthesis of Spiro-α-methylene-γ-lactams via Chiral Quaternary 3-Aminooxindole Adducts Accessed by Zn-Mediated Allylation of Sulfinyl Ketimines

“…14 For chiral 3-allyl-3-aminooxindoles, Silvani developed MgBr 2 promoted allylation of isatin derived chiral tert-butanesulfinyl ketimines by Grignard addition. 15 Subsequently, Zn-mediated addition of allyl bromide to isatin derived chiral N-tert-butanesulfinyl ketimines was realized by Xu. 16 Recently, our group also explored the reactions of isatin derived N-tert-butanesulfinyl ketimines for asymmetric preparation of synthetically important chiral amines.…”

Crystal structures of amino acids: from bond lengths in glycine to metal complexes and high-pressure polymorphs

“…[ [30] and dl-2-ammonio-3-(trimethylsilyl)propanoate (KUMKAF). [88] Alternatively, water molecules may be incorporated as parts of the hydrogen bonding network. This can happen in a number of different ways, Figure 12 shows one example observed for two fluorinated derivatives of l-Phe (EXAXAC and EXAXIK).…”