Multi‐Step Continuous Flow Synthesis of β/γ‐Substituted Ketones

Abstract

The smooth preparation of β/γ‐substituted ketones has been carried out by using a three‐step continuous flow synthesis involving the initial photocatalyzed addition of an aldehyde onto phenyl vinyl sulfone. The resulting β‐ketosulfones were then elaborated in flow to prepare in situ an enone upon basic elimination of the sulfonyl group and then to give γ‐nitroketones, a 4‐chromanone, and β‐(3‐indolyl)ketones in moderate to good yields.

Direct Photocatalyzed Hydrogen Atom Transfer (HAT) for Aliphatic C–H Bonds Elaboration

“…The environmental performance of these acylations was further ameliorated making use of continuous flow conditions . The adoption of this operation mode also allowed design of multistep procedures, wherein the photocatalytic C­(sp 2 )–C­(sp 3 ) bond formation was followed by additional thermal steps on the resulting acylated derivatives. , …”

“…382 The adoption of this operation mode also allowed design of multistep procedures, wherein the photocatalytic C(sp 2 )−C(sp 3 ) bond formation was followed by additional thermal steps on the resulting acylated derivatives. 435,436 An elegant one-pot protocol comprised of two distinct photochemical steps was adopted for the preparation of homoallyl ketones starting from cyclopentanones and electronpoor olefins. The sequence involved an initial Norrish type-I photoinduced fragmentation of the 5-membered ring to give a 4-pentenal derivative followed by the TBADT-photocatalyzed hydroacylation of an electron-poor olefin.…”

Technological Innovations in Photochemistry for Organic Synthesis: Flow Chemistry, High-Throughput Experimentation, Scale-up, and Photoelectrochemistry

“…TBADT is also known to activate aldehydes . An interesting example is reported by Fagnoni, Ravelli, and co-workers, who described the multistep synthesis of β/γ-substituted ketones starting from the addition of aldehydes onto vinyl sulfones in continuous-flow (Scheme A) . After the first TBADT-photocatalytic step (PTFE tubing, 12 mL), the subsequent desulfonylation was performed in basic conditions by adding tetramethyl guanidine to the reaction stream through a T-mixer.…”

Multi‐Step Continuous‐Flow Organic Synthesis: Opportunities and Challenges

“…The Ravellig roup achieved the synthesiso fb/g-substituted ketones under flow conditions (Figure 24). [26] This strategy used photocatalysis to allow the addition of vinyl sulfone 75 to aldehydes to produce b-ketosulfone 76.Using polystyrenesupport-ed-triazabicyclodecene (PS-TBD) and alkali, unstable enone 77 was generated in situ and quickly combined with an ucleophilic reagent to obtain the target product b-(3-indolyl) ketone 78 in moderate to good yields (20-67 %). The successo ft his reaction is partially attributed to the excellent mixing providedb y the flow microreactor,w hich allowed the immediate consumption of unstable enone and limited side reactions.…”