A Continuous‐Flow Process for Palladium‐Catalyzed Olefin Cleavage by using Oxygen within the Explosive Regime

Abstract

A continuous‐flow protocol for Pd‐catalyzed olefin cleavage by using molecular oxygen as the sole oxidant to give carbonyl compounds was explored. The developed flow protocol allowed the use of a low catalyst loading (0.1 mol %), and decomposition of the active catalyst was prevented through stabilization by poly(ethylene glycol)‐400 (PEG‐400), which was present as a cosolvent. Radical scavengers inhibited the reaction, which indicated the involvement of a free‐radical path in the reaction mechanism. The applicability of the continuous‐flow protocol was demonstrated on several olefin substrates. The continuous‐flow process enabled safe and scalable olefin cleavage.

Slurry loop tubular membrane reactor for the catalysed aerobic oxidation of benzyl alcohol

“…The selective oxidation of alcohols is of great interest in the che-mical industry [1][2][3][4], as aldehydes and ketones are valuable molecular platforms in organic synthesis, manufacture of fragrances and pre-paration of drug candidates [1,5]. From a green chemistry perspective, the utilization of pure oxygen and environmentally friendly hetero-geneous catalysts has attracted much attention [6][7][8][9][10][11][12]. In this regard, continuous flow oxidations can off er advantages, allowing for improved control over the operating parameters and safety of hazardous reactions [7,13].…”

“…Aerobic oxidation of alcohols can pose safety risks due to flamm-ability [12,13,26,27]. In this regard, various research groups have tried to address this issue by using either diluted oxygen [28,29], or micro-channel reactors which have been shown to be safe to operate [9,15,[30][31][32]. Keeping the gaseous phase oxidant separate from the organic substrate by using membrane contactors represents an alter-native solution [7,13,33,34].…”

Continuous‐flow Synthesis of Aryl Aldehydes by Pd‐catalyzed Formylation of Aryl Bromides Using Carbon Monoxide and Hydrogen

“…We also investigated the use of stabilizing solvents to prevent the formation of black Pd 0 particles. Even though environmentally their use should be minimized, polar aprotic solvents, for example, DMF and dimethylacetamide (DMA), can stabilize Pd 0 species in solution . However, using these solvents as co‐solvents did not improve conversion or yield (Table S3) and therefore not investigated further.…”

“…We knew from the outsett hat aw ell-known phenomenon, and often unavoidable process, is the aggregation of Pd 0 to form clusters that ultimately and irreversibly precipitate in the form of Pd black, which can then deposit onto the reactor wall. [27] Deposited Pd can be recovered from as tainless-steel coil by washing with 20 %a queous nitric acid solution at 60 8C. The reactor coil was always washed between experiments (unless otherwise specified) with aqueousn itric acid solution to remove residual Pd.…”

Recent Applications of Continuous Flow in Homogeneous Palladium Catalysis

“…47 In 2017, Kappe et al described a continuous flow protocol for a Pd-catalysed olefin cleavage using gaseous oxygen. 48 The applicability of this flow transformation was demonstrated on several olefin substrates to yield the corresponding carbonyl compounds in moderate to excellent yields (Scheme 31). The flow protocol used a low catalyst loading (0.1 mol%), while decomposition of the active catalyst species was prevented via stabilisation by PEG 400 .…”