Continuous-flow enantioselective α-aminoxylation of aldehydes catalyzed by a polystyrene-immobilized hydroxyproline

Abstract

SummaryThe application of polystyrene-immobilized proline-based catalysts in packed-bed reactors for the continuous-flow, direct, enantioselective α-aminoxylation of aldehydes is described. The system allows the easy preparation of a series of β-aminoxy alcohols (after a reductive workup) with excellent optical purity and with an effective catalyst loading of ca. 2.5% (four-fold reduction compared to the batch process) working at residence times of ca. 5 min.

Pursuing Chemical Efficiency by Using Supported Organocatalysts for Asymmetric Reactions under Aqueous Conditions

“…Resin 5 was recovered by filtration and reused three times affording similar results [56]. This resin was also deployed under continuous flow in the presence of organic solvents for other enantioselective transformations [57]. The attachment of the proline moiety directly through the 1,2,3-triazole linker (resin 6, Figure 1) allowed the establishment of a hydrogen-bond-based aqueous microphase around the hydrophobic resin.…”

Catalytic Enantioselective Flow Processes with Solid‐Supported Chiral Catalysts

“…Encouraged by these results, we decided to explore the generality of the concept, so we moved to the α‐oxidation of aldehydes using nitrosobenzene as the electrophile. A related packed bed reactor filled with 2 turned out to be very active and in 5 min residence time the desired products were obtained in good conversions (Figure ). However, the practicality of this process was hampered by a side reaction of the catalyst that led to deactivation of the resin.…”

Synthesis and catalytic applications of C3-symmetric tris(triazolyl)methanol ligands and derivatives

“…48 The PS-supported derivative 21a has been used in the highly enantioselective α-aminoxylation of aliphatic aldehydes under continuous flow conditions. 48 The same organocatalytic system was previously applied to the asymmetric α-aminoxylation of aldehydes and ketones under bath conditions, 49 for the direct enantioselective aldol reactions in batch 41,47 and for highly enantioselective, syn-diastereoselective Mannich reactions in batch and flow.…”

“…48 The PS-supported derivative 21a has been used in the highly enantioselective α-aminoxylation of aliphatic aldehydes under continuous flow conditions. 48 The same organocatalytic system was previously applied to the asymmetric α-aminoxylation of aldehydes and ketones under bath conditions, 49 for the direct enantioselective aldol reactions in batch 41,47 and for highly enantioselective, syn-diastereoselective Mannich reactions in batch and flow. 50 Another immobilised chiral proline derivative (21b), which contains a longer spacer between the triazole ring and the polymer backbone, was designed for higher catalytic activity and allowed the development of the first practical flow version of highly enantioselective aldol reactions.…”