New Diastereoselective Synthesis of 3-Alkylidene-1-methyloxindoles

Abstract

Addition of alkyl or aryl α-substituted acetophenones to N-methylisatin in basic media gives diastereomeric mixtures of the corresponding α-substituted 3-benzoylmethyl-3-hydroxy-1-methyloxindole in good yields. Under anhydrous conditions (concentrated sulfuric acid at 0 °C) these adducts eliminate benzoic acid, instead of water, to give pure (E)-3-alkylidene derivatives in quantitative yield. Applying the same treatment to the α-unsubstituted analogue, dehydration took place to give pure (Z)-3-benzoylmethylen-1-methyloxindole.

Key words

indoles - addition reactions - eliminations - rearrangements - isatinylidenes

References

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8

Compound (Z)-3 has been obtained in Ref.^5e by isomerization of (E)-3 in the presence of AlCl₃.

9

Both isomers are clearly distinguished by the chemical shift of their H(3α)-protons.

11

A mutual NOE between H-4 and (3α)-methyl protons characterized the Z-isomer.