α-Arylation of (hetero)aryl ketones in aqueous surfactant media

Abstract

α-Arylations can be run under micellar catalysis conditions using a Pd(i) pre-catalyst together with KO-t-Bu as base. Sequences using this coupling along with as many as four additional steps can be carried out in a 1-pot fashion, all in water.

Allylations of aryl/heteroaryl ketones: neat, clean, and sustainable. Applications to targets in the pharma- and nutraceutical industries

“…15 Hence, given that the anticipated proton abstraction "in water" has already been achieved, 13 it was rather unexpected to find that absolutely none of the α-allylated ketone had formed upon replacing catalytic Pd/aryl bromide with an allylic bromide; indeed, the same ketone, aqueous medium, and base were present as used previously (in α-arylations) with considerable success. 13 All attempts to alter each of the reaction variables did nothing to change the outcome. It became quite clear that in this case, "chemistry in water" was not applicable (Table 1).…”

“…13,14 Although this approach seems counterintuitive, it is enabled by use of designer surfactant TPGS-750-M, where nanomicelles derived from this amphiphile form a hydrophobic inner core in which the enolization/α-allylation could occur. 15 Hence, given that the anticipated proton abstraction "in water" has already been achieved, 13 it was rather unexpected to find that absolutely none of the α-allylated ketone had formed upon replacing catalytic Pd/aryl bromide with an allylic bromide; indeed, the same ketone, aqueous medium, and base were present as used previously (in α-arylations) with considerable success. 13 All attempts to alter each of the reaction variables did nothing to change the outcome.…”

Cascade Processes with Micellar Reaction Media: Recent Advances and Future Directions

“…Without isolation of the intermediates, the aldehyde was generated, reduced to the benzylic alcohol, and treated with 2-chloronicotinonyl chloride to achieve the desired ester product ( Figure 9 ). The product was isolated by extraction with ethyl acetate and further purified by flash chromatography, resulting in a 66% isolated yield [ 127 ].…”

“…The product was recovered by extraction with ethyl acetate and flash chromatography, with an overall isolated yield of 66%. Adapted from [ 127 ] with permission.…”

Multicomponent Bifunctionalization of Methyl Ketones Enabled by Heterogeneous Catalysis and Solar Photocatalysis in Water

“…Over the past few decades, significant advances have been achieved in developing novel and efficient methods for the synthesis of α-functionalized ketones because such compounds are versatile intermediates for the construction of a variety of natural products, advanced materials, as well as pharmaceuticals and related compounds. , Recently, the direct C­(sp 3 )-H functionalization reactions have been regarded as a promising approach for the α-functionalization of ketones due to their advantages such as atom- and step-economy. Based on this strategy, various solutions to the formation of α-functionalized ketones have been provided, including the iodine-promoted transformation, − transition metal catalysis, − and so on. − For example, Maulide’s group in 2020 reported a triflic anhydride-mediated α-arylation of acetophenones via metal-free electrophilic activation (Scheme a, top) . Later, Nishikata and co-workers developed an efficient copper-organocatalyst system for the C–H alkylation of ketones (Scheme a, middle) .…”