Scalable Process for Reduction of Aromatic Carboxylic Acids to Aldehydes via Pinacolborane

The transformation of carboxylic acids to their corresponding aldehydes is one of the most important reactions in both organic syntheses and industrial applications. Our previous research reported an efficient and convenient aldehyde preparative method via controllable reduction of carboxylic acids with pinacolborane (HBpin/DMAP). However, the new method still suffered from some limitations during scaling-up, for example, a large excess of reagents, obvious exotherms, and silica gel column purification. The process development was performed to address these troublesome issues and also to make the new method a practical synthetic protocol. After the detailed exploration of reaction parameters, including the reaction conditions, charging mode, and workup methods, a safe, efficient, and column-free process of reduction of aromatic carboxylic acids to aldehydes via DMAP/HBpin has been successfully established. The newly developed robust process could provide a practical and alternative method for straightforward access of aldehydes from carboxylic acids.