Synthesis of a spirocyclic indoline lactone

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Heterocyclic Chemistry

Background:

• Previous studies reported failed cyclization of ethyl [2-(4-methoxybenzylideneamino)phenyl]acetate under basic conditions.
• The tert-butyl ester analog was investigated to explore alternative reaction pathways.

Purpose of the Study:

• To investigate the base-promoted cyclization and C3-alkylation of tert-butyl [2-(benzylideneamino)phenyl]acetate.
• To synthesize and characterize the resulting dihydroindole derivative and a spirocyclic lactone.
• To reconcile conflicting results regarding the cyclization of related esters.

Main Methods:

• Base-promoted cyclization of tert-butyl [2-(benzylideneamino)phenyl]acetate.
• C3-alkylation using allyl bromide.
• N-acylation, olefin dihydroxylation, and tert-butyl ester cleavage to form a spirocyclic lactone.
• Isolation and characterization of diastereomers using spectroscopic methods.

Main Results:

• High yield synthesis of 3-allyl-2-phenyl-2,3-dihydro-1H-indole-3-carboxylic acid, tert-butyl ester (15b) as a single diastereomer.
• Successful formation of a spirocyclic lactone (18) as a pair of diastereomers.
• Demonstrated successful cyclization contrary to prior literature for analogous ethyl esters.

Conclusions:

• The tert-butyl ester moiety facilitates successful base-promoted cyclization and C3-alkylation, unlike the ethyl ester.
• The synthetic route provides access to functionalized dihydroindole derivatives and spirocyclic lactones.
• This work clarifies discrepancies in the literature regarding the cyclization of these specific ester derivatives.