Pd-Catalyzed Chemoselective O‑Benzylation of Ambident 2‑Quinolinone Nucleophiles

We have discovered and developed a highly chemoselective
O-benzylation
of ambident 2-quinolinone nucleophiles via Pd-catalysis. Detailed
reaction analysis using direct-injection high resolution mass spectrometry
(DI-HRMS) combined with in situ 31P NMR implicate a phosphine
mono-oxide Pd­(II) η1-benzyl complex as a key intermediate
on the catalytic cycle. Extrapolation of this method to selectively
O-alkylate a series of substituted 2-quinolinones using several benzylic
electrophiles is demonstrated providing 2-benzyloxy quinolines in
good yields and high O:N selectivities (up to 100:1) utilizing as
little as 1 mol % Pd-catalyst to achieve these results.