# Ligand flexibility as a concept to unlock catalytic activity: acyclic carbenes for base-free transfer ruthenium hydrogenation catalysis

## TL;DR

Flexible acyclic carbene ligands enable base-free hydrogenation reactions, allowing the use of sensitive substrates that are incompatible with traditional methods.

## Contribution

The introduction of acyclic (diamino)carbene ligands provides a novel approach to base-free transfer hydrogenation catalysis.

## Key findings

- Acyclic (diamino)carbene ligands enable high catalytic activity in base-free transfer hydrogenation with turnover numbers >1000.
- Base-free conditions allow hydrogenation of substrates containing base-sensitive groups like esters and amides.
- Late-stage hydrogenation of complex substrates is now possible without the complications of strong bases.

## Abstract

Many ligands are structurally rigid and well-defined, e.g. N-heterocyclic carbenes display a fan-like structure with a defined buried volume. Here, we break this dogma by introducing more flexibility around the catalytically active center by using acyclic (diamino)carbene (ADC) ligands. The ADC ligand was constructed in a straightforward protocol on the ruthenium center via methyl isocyanide coordination and subsequent reaction with amines such as pyrrolidine. Ligand flexibility in the formed (pyrrolidine)(methylamine)carbene ruthenium complex Ru-2 was demonstrated both in solution (variable temperature NMR) and in the solid state through crystallographic identification with the protic NH site oriented either distal or proximal to the ruthenium center. In contrast to their cyclic analogues, the Ru-ADC complexes are highly active in base-free transfer hydrogenation, with turnover numbers >1000. The base-free conditions allowed for the transformation of substrates with base-sensitive groups such as esters, amides, acids, and amines, substrates that typically fail to undergo transfer hydrogenation under classical conditions. The absence of base also enabled late-stage hydrogenation of more complex substrates, and it avoids complications such as corrosion attributed to KOH and related strong bases.

Acyclic (diamino)carbene ligands impart flexibility and allow for protic units to be inserted proximal to a catalytic metal center, which enables base-free transfer hydrogenation of substrates that are incompatible with classic conditions.