One-Pot C–H Arylation/Lactamization Cascade Reaction of Free Benzylamines

An
efficient method has been developed for the synthesis of seven-membered
biaryl lactams involving Pd-catalyzed, native amine-directed, ortho-arylation of benzylamines followed by in situ lactamization. This cascade sequence is enabled by the use of 2-iodobenzoates,
which facilitates C–H arylation from the free amine under conditions
that typically require an improved directing group approach. This
reaction is characterized by a broad substrate scope with good functional
group tolerance. The need for an ester versus carboxylic acid-functionalized
coupling partner is also explored, as is the potential for synthesizing
eight-membered biaryl lactams. Various applications are also investigated,
including access to the aza-brassinolide core.