Continuous-Flow Asymmetric Aldol Reactions Using Sawdust-Supported Cross-Linked L-Proline Catalysts

Abstract

Cross-linked L-proline immobilized on polymaleated octadecene (PMHC18-L-pro-CL) was developed as a robust heterogeneous catalyst for asymmetric Aldol reactions and evaluated under both batch and continuous-flow conditions. Although the polymer exhibited partial gelation in DMSO during batch operation, blending with sawdust generated a mechanically stable, permeable packed bed that enabled gravity-driven flow without external pumping, thereby functioning as a pump-optional catalytic evaluation platform. The optimized 50:50 sawdust/polymer bed afforded quantitative conversion, a 97:3 syn:anti ratio, and >90% ee in a single 53 min residence time. Mass-normalized TON/TOF values were determined (TON = 3.4, TOF = 0.14 h⁻¹ in batch; TON = 0.05, TOF = 0.05 h⁻¹ under flow), and contextualized against representative heterogeneous proline catalysts. Axial-dispersion analysis indicated near-plug-flow behavior, consistent with the reproducible ee/dr across cycles and the absence of channeling. A preliminary multi-tubular reactor model (Fig. 5) was developed to assess industrial feasibility, suggesting that the packed-bed concept can be scaled using multiple small-diameter tubes. Overall, this gravity-assisted sawdust-stabilized reactor provides a simple, low-energy, pump-optional platform for early-stage continuous-flow organocatalysis and offers mechanistic and engineering insights relevant to future scale-up.