Switchable C2/C3 positional selectivity of thioisatins in a three-component domino reaction: combined computational and experimental studies.
Org Biomol Chem
; 20(48): 9639-9644, 2022 12 14.
Article
em En
| MEDLINE
| ID: mdl-36411991
ABSTRACT
The nucleophile-induced domino reaction is a featured reactivity mode of thioisatin, but the C2/C3 positional selectivity towards a nucleophile has not been understood in-depth. In this work, a domino reaction of thioisatin with bromoacetophenone and tryptamine hydrochloride to produce a benzothiophene-fused eight-membered N-heterocycle was described, showing that the Brønsted acid-base form of the amine partner was crucial for the selectivity, because using tryptamine instead of tryptamine hydrochloride gave a different product. Control experiments and density functional calculations revealed that the domino reaction using tryptamine or tryptamine hydrochloride was triggered by a condensation reaction at the C2 or C3 position of thioisatin, respectively. A delicate balance between local electrophilicity and polarization effect may be responsible for the observed selectivity.
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1
Base de dados:
MEDLINE
Assunto principal:
Triptaminas
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article