Catalytic Enantioselective Birch-Heck Sequence for the Synthesis of Phenanthridinone Derivatives with an All-Carbon Quaternary Stereocenter.
J Org Chem
; 87(2): 1154-1172, 2022 01 21.
Article
en En
| MEDLINE
| ID: mdl-34985891
ABSTRACT
Novel phenanthridinone analogues with an all-carbon quaternary stereocenter have been enantioselectively synthesized using the Birch-Heck sequence. Flat phenanthridinone structures have extensive bioactivity but consequently also suffer from poor therapeutic selectivity. The addition of a quaternary center to the phenanthridinone skeleton has the potential to generate more complex analogues with improved selectivity. Unfortunately, no general synthetic pathway to such derivatives exists. Herein we report a four-step process that transforms inexpensive benzoic acid into 22 different quaternary carbon-containing phenanthridinone analogues with a variety of substituents on all three rings alkyl groups at the quaternary center; methyl, methoxymethyl, or para-methoxybenzyl on the amide nitrogen; and halogen and methyl substituents on the aryl ring. Good to very good enantioselectivity was demonstrated in the key intramolecular desymmetrizing Mizoroki-Heck reaction. Transformations of the Heck reaction products into molecules with potentially greater therapeutic relevance were also accomplished.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Carbono
/
Betula
Idioma:
En
Revista:
J Org Chem
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos