Synthesis of ketones via organolithium addition to acid chlorides using continuous flow chemistry

Abstract

An efficient method for the synthesis of ketones using organolithium and acid chlorides under continuous flow conditions has been developed.

In Situ Reaction Monitoring of Unstable Lithiated Intermediates through Inline FTIR Spectroscopy

“…Concerning laboratory experiments, many authors successfully synthesized a variety of organolithium compounds within microstructured devices, by taking advantage of precisely adjustable reaction conditions to easily control those highly exothermic and fast reactions [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. Key examples are studies by the groups of Yoshida, Feng, and Browne, as shown below.…”

Continuous flow synthesis of diaryl ketones by coupling of aryl Grignard reagents with acyl chlorides under mild conditions in the ecofriendly solvent 2-methyltetrahydrofuran

“…[36][37][38] Recently, the Jamison group described an efficient continuous ow synthesis of ketones from carbon dioxide and organolithium or Grignard reagents at ambient temperature and pressure. 39 The Kim group developed an efficient method for the synthesis of ketones using organolithium reagents and acid chlorides under continuous ow conditions at À40 C. 40 Unfortunately, most of the solvents used in the synthesis of diaryl ketones are not environmentally friendly. In recent years there has been a trend towards the use of bio-derived, green solvents as replacements for hazardous and/or environmentally-damaging solvents.…”

Flow Technology for the Genesis and Use of (Highly) Reactive Organometallic Reagents

“…The flow process could be efficiently applied to aryllithiums, alkenyllithiums as well as alkynyllithiums. In a similar way, Kim developed the synthesis of ketones by a continuous flow addition of organolithiums to acylchlorides (Scheme b) . In both processes, the high level of chemocontrol, with respect to batch processing, is a consequence of the accurate control of the reaction parameters applied in the flow microreactor systems.…”

“…In as imilar way,K im developed the synthesis of ketones by ac ontinuous flow addition of organolithiumst oa cylchlorides (Scheme 12 b). [34] In both processes, the high level of chemocontrol, with respectt ob atch processing, is ac onsequence of the accurate controlo ft he reaction parameters appliedi nt he flow microreactor systems. It is worth mentioning that the formation of the tertiarya lcohol is very difficult to controlu nder batch conditions, even if the reaction is performed at very low temperature.…”