Unexpected Substituent Effects in Spiro-Compound Formation: Steering N-Aryl Propynamides and DMSO toward Site-Specific Sulfination in Quinolin-2-ones or Spiro[4,5]trienones.
J Org Chem
; 86(14): 9490-9502, 2021 07 16.
Article
in En
| MEDLINE
| ID: mdl-34184892
ABSTRACT
A highly substituent-dependent rearrangement allows for the novel and SOCl2-induced divergent synthesis of 3-methylthioquinolin-2-ones and 3-methylthiospiro[4.5]trienones through intramolecular electrophilic cyclization of N-aryl propyamides. DMSO acts as both solvent and sulfur source, and use of DMSO-h6/d6 enables the incorporation of SCH3 or SCD3 moieties to the 3-position of the heterocyclic framework. Different para-substituents trigger divergent reaction pathways leading to the formation of quinolin-2-ones for mild substituents and spiro[4,5]trienones for both electron-withdrawing and -donating substituents, respectively. On the basis of both computational and experimental results, a new mechanism has been put forward that accounts for the exclusive spirolization/defluorination process and the surprising substituent effects.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Spiro Compounds
/
Dimethyl Sulfoxide
Language:
En
Journal:
J Org Chem
Year:
2021
Type:
Article
Affiliation country:
China