A convenient enantioselective CBS-reduction of arylketones in flow-microreactor systems

Abstract

A convenient, versatile, and green CBS-asymmetric reduction of aryl and heteroaryl ketones has been developed by using the microreactor technology. The study demonstrates that it is possible to handle borane solution safely within microreactors and that the reaction performs well using 2-MeTHF as a greener solvent.

Recent advancements on the use of 2-methyltetrahydrofuran in organometallic chemistry

“…The same Luisi’s group exploited the combination of using, in flow technology, 2-MeTHF for the synthesis of enantioenriched alcohols via the Corey–Bakshi–Shibata (CBS) oxazaborolidine-mediated reduction of the prochiral ketones [61]. Under the optimized reaction conditions, the process reached to completion within few minutes, thus providing the desired asymmetric targets in up to 99% yield and 91:9 enantiomeric ratio ( er ) (Scheme 5).…”

Enzymatic synthesis of nucleoside analogues from uridines and vinyl esters in a continuous-flow microreactor

“…Moreover, unique reactivities and selectivities are sometimes observed under continuous-ow conditions. 11,12 As a result of the outow of products, overreactions are avoided, and catalyst/substrate conditions in continuous-ow systems can increase the reactivity and selectivity. The separation of catalysts and products is very easy when heterogeneous catalysts are packed in continuous-ow columns.…”

A Practical 11B NMR Evaluation of BH3 Titer in Commercial Solutions

“…Borane (BH 3 ) is a widely employed reagent in organic synthesis. Usually, BH 3 is generated from stable salts (i.e., NaBH 4 or LiBH 4 ) or can be directly used as solutions of its complexes (i.e., BH 3 •THF or BH 3 •SMe 2 , henceforth abbreviated as BH 3 •DMS). However, the growing industrial interest on borane as reducing agent needs efforts to clarify the titer and stability of such complexes in solution.…”

“…However, the growing industrial interest on borane as reducing agent needs efforts to clarify the titer and stability of such complexes in solution. For example, commercially available solutions of BH 3 •THF have tremendous importance in reductions or hydroboration-oxidation protocols as well as other transformations. 1 Reduction of amides, ketones, alkynes, alkenes, all occur using BH 3 •THF or BH 3 •DMS as reducing agents or other sources of BH 3 .…”

“…Recently, we came across this issue during the development of a sustainable protocol for the asymmetric reduction of aryl ketones in a microfluidic device. 3 In the microflow system, it was possible to handle safely the in situ generated borane CBS-oxazaborolidine complex using a green solvent such as 2-methyltetrahydrofuran (2-MeTHF), and without using conventional stabilizers. During the optimization of the flow process, we needed a reliable method for establishing the exact titer of BH 3 in commercial solutions in order to deliver the right amount inside the microreactor.…”