Unlocking geminal fluorohaloalkanes in nucleophilic fluoroalkylation chemistry: generation and trapping of lithiumfluorocarbenoids enabled by flow microreactors

Abstract

A direct nucleophilic monofluoroalkylation strategy leveraging on lithium fluorocarbenoids has been developed. Flow microreactor technology allows capitalizing the synthetic potential of these scarcely explored short-lived intermediates – namely 1-fluoro-2-phenylethyllithium, 1-fluoro-3-phenylpropyllithium,...

Micro-flow heteroatom alkylation via TfOH-mediated rapid in situ generation of carbocations and subsequent nucleophile addition

“…Precise control of short periods of reaction time (<1 s) and temperature can be achieved utilising micro-flow technology. 8 We have developed efficient micro-flow syntheses for producing valuable organic compounds. 9 Recently, we reported the rapid generation of a highly active indolylmethyl electrophile and its nucleophilic substitution in a micro-flow reactor.…”

Synthesis of Alcohols: Streamlined C1 to Cn Hydroxyalkylation through Photoredox Catalysis

“…Mindful of the inherent challenges posed by batch photocatalytic methods at scale, our subsequent objective was to transition this hydroxyalkylation reaction to a continuous-flow platform. 45,46,47 Based on our expertise in microfluidic technology, 48,49,50 we identified some issue in the batch protocol that would hinder transitioning to a flow process. Firstly, the heterogeneous nature of the reaction mixture would result in nonuniform irradiation and limited light penetration when operating at larger scales.…”

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

“…Flow chemistry [52][53][54][55][56] involving the employment of continuous-flow reactors in the past decade has proven to be a powerful alternative to batch reactor systems to increase both yields and selectivity [57] in chemical reactions. This technological advancement has proven to be advantageous as it allows reactions to be performed under safe working conditions [58,59] (hazardous and reactive substrates can also be handled safely) [60,61], as well as shortening the process time compared to the batch process. Furthermore, automation of parameters such as temperature and pressure can help with reproducibility in continuous flow reactors compared to classical batch techniques [62,63].…”