Jason Williams

Synlett
DOI: 10.1055/s-0037-1611054

Palladium-catalyzed bond-forming reactions, such as the ­Suzuki–Miyaura and Mizoroki–Heck reactions, are some of the most broadly utilized reactions within the chemical industry. These reactions frequently employ hazardous solvents; however, to adhere to increasing sustainability pressures and restrictions regarding the use of such solvents, alternatives are highly sought after. Here we demonstrate the utility of dimethyl isosorbide (DMI) as a bio-derived solvent in several benchmark Pd-catalyzed reactions: Suzuki–Miyaura (13 examples, 62–100% yield), Mizoroki–Heck (13 examples, 47–91% yield), and Sonogashira (12 examples, 65–98% yield).
[...]

© Georg Thieme Verlag Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

Get in line! The immobilization of Rose Bengal (RB) onto mesoporous silica nanoparticles (MSNs) enabled the ¹O₂ photooxygenation of various organic substrates under microfluidic conditions upon irradiation with 540 nm LEDs. An improved resistance to photobleaching was obtained and the heterogenized photosensitizer could be easily recovered from the reactor effluent by in‐line membrane separation.

Abstract

Continuous flow photochemistry relying on photosensitizers faces two main challenges: 1) Photodegradation (bleaching) and 2) the downstream removal of the photosensitizer. Rose bengal (RB) is a common photosensitizer utilized for photooxygenation reactions with singlet oxygen (¹O₂), but is notoriously sensitive to photobleaching and difficult to remove from reactor effluents. The heterogenization of photosensitizers on mesoporous silica nanoparticles (MSNs) is arguably a viable option for such applications. Herein, we report on the use of RB covalently incorporated into MSNs (RB@MSNs) for photooxygenation reactions under continuous flow conditions. RB@MSNs enable the ¹O₂ photooxygenation of various organic substrates upon irradiation with 540 nm LEDs. A series of organic substrates were evaluated including methionine, α‐terpinene, 2‐furoic acid, triphenylphosphine, citronellol and cyclopentadiene. These results emphasize an improved resistance to photobleaching, and the possibility to use RB@MSNs as an easily recoverable catalyst, which could be removed from the reactor effluent either a) by centrifugation or b) by in‐line membrane filtration.

Shine on: The generation of a 2‐oxazolidinone intermediate from protected phenylalanine requires a light‐induced benzylic bromination as the key step. A continuous flow photochemical procedure has been developed to enable the large‐scale production of the target compound.

Abstract

A continuous flow procedure for the benzylic photobromination of methyl N,N‐bis (tert‐butoxycarbonyl) phenylalaninate is presented. This photochemical transformation generating the brominated intermediate is the critical step in the synthesis of the oxazolidinone methyl (4S,5R)‐3‐N‐tert‐Butoxycarbonyl‐5‐phenyl‐1,3‐oxazolidin‐2‐oxo‐4‐carboxylate, a key intermediate for the preparation of active pharmaceutical ingredients. The reaction was optimized in three continuous flow photoreactors: A self‐made reactor based on a T5 8 W black light lamp, as well as the commercially available VapourTec® UV‐150 and Corning® Advanced‐Flow™ reactors, both equipped with LED light sources. Under optimal conditions, concentrated solutions (95 g/L) of the starting material could be processed on a multi‐gram scale, providing high conversion (96 %) within 7 min at 30 °C, using 2 equivalents of N‐bromosuccinimide (NBS).