Membrane-based TBADT recovery as a strategy to increase the sustainability of continuous-flow photocatalytic HAT transformations

Abstract

Photocatalytic hydrogen atom transfer (HAT) processes have been the object of numerous studies showcasing the potential of the homogeneous photocatalyst tetrabutylammonium decatungstate (TBADT) for the functionalization of C(sp3)–H bonds. However, to translate these studies into large-scale industrial processes, careful considerations of catalyst loading, cost, and removal are required. This work presents organic solvent nanofiltration (OSN) as an answer to reduce TBADT consumption, increase its turnover number and lower its concentration in the product solution, thus enabling large-scale photocatalytic HAT-based transformations. The operating parameters for a suitable membrane for TBADT recovery in acetonitrile were optimized. Continuous photocatalytic C(sp3)-H alkylation and amination reactions were carried out with in-line TBADT recovery via two OSN steps. Promisingly, the observed product yields for the reactions with in-line catalyst recycling are comparable to those of reactions performed with pristine TBADT, therefore highlighting that not only catalyst recovery (>99%, TON > 8400) is a possibility, but also that it does not happen at the expense of reaction performance.

Rapid plugged flow synthesis of nucleoside analogues via Suzuki-Miyaura coupling and heck Alkenylation of 5-Iodo-2’-deoxyuridine (or cytidine)

“…Furthermore, automation of parameters such as temperature and pressure can help with reproducibility in continuous flow reactors compared to classical batch techniques [62,63]. Research groups of Ley [64][65][66], Kappe [67][68][69], Noel [70][71][72] have made significant contributions to the microreactor flow technology for synthesis. More recently, the Hilton group has been using microreactor flow technology [73][74][75] popular with both chemical and process engineers [76,77].…”

Ring‐Opening Coupling Reaction of Cyclopropanols with Electrophilic Alkenes Enabled by Decatungstate as Photoredox Catalyst

“…[62,63] Recently, TBADT recycling strategy by nanofiltration was developed by the group of Noёl, allowing to use TBADT-photocatalyzed reactions at industrial scale. [64] After a brief optimization (see Tables S4 and S5 in the Supporting Information), we were able to prepare compounds 3 aa and 3 la in good 74-75% yields and gram amounts with 20-30 min of residence time. Owing to the limited solubility of TBADT in dichloromethane, acetonitrile was employed as a solvent under continuous-flow conditions.…”

“…Flow chemistry is especially advantageous for performing photochemical transformations, since it ensures more efficient light irradiation, consistency of results, and scalability among other benefits [62,63] . Recently, TBADT recycling strategy by nanofiltration was developed by the group of Noёl, allowing to use TBADT‐photocatalyzed reactions at industrial scale [64] . After a brief optimization (see Tables S4 and S5 in the Supporting Information), we were able to prepare compounds 3 aa and 3 la in good 74–75% yields and gram amounts with 20–30 min of residence time.…”

Inline purification in continuous flow synthesis – opportunities and challenges

“…Interestingly, another vacuum Teflon membrane is used to remove the ethylene that is produced as byproduct in the metathesis reaction. Some subsequent publications include the Pd-complex removal after a Suzuki coupling [126], a Heck catalyst retention with reverse boiling-point-order solvent exchange [127], and a membrane for recovery of the photocatalyst TBADT (tetrabutylammonium decatungstate) [128]. Organic solvent inline nanofiltration is an interesting green approach for solvent recovery that also concentrates, and thus improves the purity of the target compounds.…”