Phenolic Activation in Chiral Bronsted Acid-Catalyzed Intramolecular α-Amidoalkylation Reactions for the Synthesis of Fused Isoquinolines.

ABSTRACT: An organolithium addition-intramolecular α-amidoalkylation sequence on N-phenethylimides has been developed for the synthesis of fused tetrahydroisoquinoline systems using 1,1'-bi-2-naphthol (binol)-derived Brønsted acids. This transformation is the first in which activated benzene derivatives are used as internal nucleophiles, instead of electron-rich heteroaromatics, generating a quaternary stereocenter. Phenolic substitution on the aromatic ring of the phenethylamino moiety and the use of binol-derived N-triflylphosphoramides as catalysts are determinants to achieve reasonable levels of enantioselection, that is, up to 75% enantiomeric excess, in the α-amidoalkylation step. The procedure is complementary to the intermolecular α-amidoalkylation process, as opposite enantiom

SUBMITTER: Aranzamendi E 

PROVIDER: S-EPMC6641169 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature