A Precise Synthetic Toolbox: H-Bond-Assisted Quadruple Reactivity of o-Dimethylaminoaryloximes

TL;DR

This paper introduces a new chemical method using hydrogen bonds to create a variety of nitrogen-containing compounds from a single starting material under mild conditions.

Contribution

The study introduces a transition-metal-free synthetic toolbox using non-covalent interactions for precise and selective chemical transformations.

Findings

Hydrogen bonding activates the reactivity of o-dimethylaminoaryloximes into nitriles and nitrogen heterocycles.

The method allows selective synthesis of fused pyrazoles, isoxazoles, and pyrroles using simple acids and solvents.

The 'buttressing effect' of substituents next to the NMe2 group enhances the reaction's precision and flexibility.

Abstract

Non-covalent interactions
are a highly promising tool
for the development
of transition-metal-free chemospecific synthetic transformations.
Here, we demonstrate the implementation of non-covalent interactions
as a simple, precise, and flexible synthetic toolbox, allowing the
controlled transformation of o-dimethylaminoaryloximes
into nitriles and hard-to-reach nitrogen heterocycles under mild conditions.
This diverse reactivity is activated via hydrogen bonding and facilitated
via the “buttressing effect” of the substituents next
to the NMe2 group. All transformations require only simple
and easily available acids and solvents, which generally provide precise
control over the direction of the reaction, allowing the selective
synthesis of nitriles, fused pyrazoles, isoxazoles, and pyrroles.

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