Continuous Flow Process for Carbonyl and α,β-Unsaturated Carbonyl Compounds Reduction Using NaBH4 Solutions: Toward Implementation of Luche Reduction in Flow

Carbonyl reductions using NaBH4 are generally high-yielding and highly selective processes commonly used in organic synthesis and the pharmaceutical industry. However, the reaction is exothermic, and the stability of the NaBH4 solution is limited, resulting in long reaction times at a controlled temperature in batch reactors, which are costly and energy-intensive on a large scale. Due to the low solubility of NaBH4 or lack of stability of NaBH4 solution in protic solvents, this reducing agent is underutilized in flow synthesis. In this work, efficient reductions of ketones and aldehydes are reported for the first time in a continuous advanced-flow reactor using stabilized solutions of NaBH4 within short residence times (between 20 and 80 s) at 60 °C. This methodology was also successfully applied to perform a straightforward and easy-to-handle continuous chemoselective reduction of α,β-unsaturated carbonyl compounds in the presence of cerium(III) chloride in methanol (i.e., Luche reduction).