Access to Fused Indolines with a Quaternary N,N′‑Aminal Center: Aza-Wacker-Type Cyclization for a Telescoped Reaction Sequence

TL;DR

A new one-pot chemical process efficiently creates complex fused indoline structures with a quaternary aminal center.

Contribution

A novel aza-Wacker-type cyclization enables rapid synthesis of tricyclic indole architectures with a C2-N,N′-aminal center.

Findings

The reaction sequence uses Zn(II) and Cu(II) catalysis for bond formation and cyclization.

The method produces 9a-substituted tricyclic indoles in good to excellent yields.

The approach shows broad substrate tolerance for fused polycyclic indolines.

Abstract

A highly efficient one-pot sequence has been developed
for the
rapid construction of fused polycyclic indolines bearing a C2-N,N′-aminal quaternary center. The process, which
employs 1,2-diaza-1,3-dienes and 2-substituted indoles as key substrates,
proceeds through a Zn­(II)-catalyzed Michael addition, followed by
an intramolecular Cu­(II)-catalyzed dearomative oxidative cyclization.
This sequence enabling N–C­(sp2) bond formation via
formal C­(sp2)–H activation, azoalkene addition,
and aza-Wacker-type cyclization exhibits broad substrate tolerance
and delivers unprecedented tricyclic indole architectures (namely
9a-substituted 9,9a-dihydro-1H-pyridazino­[3,4-b]­indoles) in good to excellent yields.

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