# Strong Hydrogen Bond Donating Solvents Accelerate the Passerini Three-Component Reaction

## TL;DR

Using a specific solvent speeds up a chemical reaction, even when using alcohol-like solvents that usually slow it down.

## Contribution

The study shows that strong hydrogen bond donating solvents can accelerate the Passerini three-component reaction.

## Key findings

- HFIP as a cosolvent increases the reaction rate of the Passerini reaction.
- Strong HBD alcohols enhance the reaction rate despite typical expectations.
- Most aprotic solvents benefit from this effect, except strong HBA solvents like DMF.

## Abstract

We report enhanced reaction rates of the Passerini reaction
(P-3CR)
using 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as a cosolvent. Although
alcoholic solvents typically increase the energy barrier of the rate-determining
step for the P-3CR, we observed significant rate enhancements even
when employing strong hydrogen bond donating (HBD) alcohols as cosolvents.
This rate enhancement was observed for most aprotic organic solvents,
with the exception of strong hydrogen bond accepting (HBA) solvents
such as DMF. Experimental kinetic studies and DFT calculations provided
a mechanistic rationale for our observations. An investigation of
the substrate scope showed that this rate enhancement generally resulted
in a (slight) increase of the overall yield in the P-3CR.