Triflylpyridinium Enables Rapid and Scalable Controlled Reduction of Carboxylic Acids to Aldehydes using Pinacolborane

Building up new and efficient methods for the controlled conversion of carboxylic acids to aldehydes is important. Herein, we report a rapid, modular and scalable method for the conversion of carboxylic acids to aldehydes using pinacolborane at ambient temperature, in which a triflylpyridinium reagent is used. The conversion of carboxylic acid to intermediate acylpyridinium by triflylpyridinium is new. A binary pyridine-coordinated boronium complex is generated after reduction. The unprecedented reduction of the acylpyridinium by HBpin opens up a practically direct synthesis of aldehydes from carboxylic acids. Theoretical studies indicate that the reduction of acylpyridinium requires a lower activation free energy than that of the product aldehyde. The synthetic advantage of this protocol is further highlighted by the scalable synthesis of aldehyde via continuous flow process. Configuration retention for chiral acids are presented in those syntheses.

Automated summary

Developing new and efficient methods for the controlled conversion of carboxylic acids to aldehydes is crucial. In this study, a rapid, modular and scalable method using pinacolborane at ambient temperature was developed. The reduction of acylpyridinium by HBpin enables the direct synthesis of aldehydes from carboxylic acids, with lower activation energy compared to the product aldehyde. The synthetic advantage of this protocol is demonstrated through scalable synthesis of aldehyde via continuous flow process.