Enantioselective Synthesis of N–N Indole-Pyrrole Atropisomers via Palladium/Chiral Phosphonic Acid Relay Catalysis

N–N
atropisomers have emerged as indispensable structural
motifs in natural products, medicinal chemistry, and asymmetric catalysis
due to their unique stereochemical properties. Herein, we introduce
an innovative synthetic methodology for the enantioselective construction
of N–N indole-pyrrole atropisomers through palladium/chiral
phosphonic acid (CPA) relay catalysis. This process involves allylic
alkylation, condensation, and dehydration between vinyl methylene
cyclic carbonates and N-amino-indoles, enabling the
efficient synthesis of structurally diverse N–N atropisomers
with excellent yields (up to 92%) and exceptional enantiocontrol (up
to 99% ee). Furthermore, biological evaluation revealed
that compounds 3ta, 3sa, 3ca, 3bd, and 3bi demonstrate potent anti-inflammatory
activity, significantly inhibiting nitric oxide (NO) production in
LPS-stimulated RAW264.7 macrophages.