Synthesis of a spirocyclic indoline lactone.
Base-promoted cyclization of tert-butyl [2-(benzylideneamino)phenyl]acetate (13a) and subsequent C3-alkylation with allyl bromide affords 3-allyl-2-phenyl-2,3-dihydro-1H-indole-3-carboxylic acid, tert-butyl ester (15b) in high yield as a single diastereomer. This result is contrary to prior publications that describe failed cyclization of an analogous ethyl ester (ethyl [2-(4-methoxybenzylideneamino)phenyl]acetate) under strongly basic conditions. N-Acylation, olefin dihydroxylation, and tert-butyl ester cleavage affords the spirocyclic lactone 18 as a pair of diastereomers. Isolation and characterization of individual diastereomers 18a and 18b are described.
Hodges
John C
JC
Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, Michigan 48105, USA. jack.hodges@pfizer.com
Wang
Wei
W
Riley
Frank
F
D000215:Acylation; D000478:Alkylation; D003500:Cyclization; D007211:Indoles / Q000138:chemical synthesis*; D007783:Lactones / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013141:Spiro Compounds / Q000138:chemical synthesis*; D013237:Stereoisomerism
C486097:5-(hydroxymethyl)-2-oxo-2'-phenyl-4,5-dihydrospiro(furan-3,3'-indole)-1'-(2'H)-carboxylic acid, methyl ester; D007211:Indoles; D007783:Lactones; D013141:Spiro Compounds