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 enantiomers are formed, and to the Pictet−
Spengler cyclization, which allows the formation of tertiary stereocenters