Direct synthesis of alkylated 4-hydroxycoumarin derivatives via a cascade Cu-catalyzed dehydrogenation/conjugate addition sequence

Abstract

An efficient approach for the direct synthesis of alkylated 4-hydroxycoumarin derivatives via Cu-catalyzed cascade dehydrogenation/conjugate addition sequence staring from simple saturated ketones and 4-hydroxycoumarins has been developed. This protocol features...

Copper-catalyzed dehydrogenative cyclization/alkenylation towards dihydroquinolinones

“…To examine the feasibility of the sequential reaction as presented in Scheme 1, the reaction was performed utilizing ketone 1A (1.0 mmol), CuBr (10 mol%), 1,10-phen (10 mol%), and TEMPO 39 (10 mol%) in DMSO at 100 °C for 10 h; then 1,3-cyclohexanedione 2A (1.5 mmol) and NH 4 Cl (10.0 mmol) were added and the reaction was continued at 100 °C for 5 h. Subsequently, the reaction mixture was treated with p -methoxy benzyl alcohol 3A (1.0 mmol), and heating was continued for an additional 15 h. We observed a 12% yield of the final product 4A (Table 1, entry 1). Likewise, a trace of the final product was observed even after changing the ligand to terpyridine, 2,2′-bipyrazine, or 2,2′-bipyridyl (Table 1, entries 2–4).…”

Iodoarene-directed photoredox β-C(sp3)–H arylation of 1-(o-iodoaryl)alkan-1-ones with cyanoarenes via halogen atom transfer and hydrogen atom transfer

“…2,3 In contrast to the well-explored arylation of C(sp 3 )–H bonds at the α-position in carbonyl compounds, 1,2 direct arylation of C(sp 3 )–H bonds at the β-position or at remote positions in the carbonyl compounds is largely underdeveloped and remains a great challenge in site selectivity control due to the competitive reactions, such as the more acidic α-C(sp 3 )–H bond arylation. 3–6 Typically, transition-metal-catalyzed chelation-assisted β-C(sp 3 )–H arylation reactions as reliable methods for producing β-aryl carbonyl systems have been intensively developed, where the vast majority of which concerned directing group (DG)-possessing amides, 3,4 a – d and ketones/aldehydes (using amino-acid based transient directing groups). 4 e – m Alternatively, the β-C(sp 3 )–H arylation of ketones and esters via α,β-dehydrogenation using transition-metal redox catalysis obviating the need for the directing group installation and removal redundant phases has been developed.…”

Palladium-Catalyzed β-C(sp3)–H Arylation of Silyl Prop-1-en-1-ol Ethers with Aryl Halides: Entry to α,β-Unsaturated Ketones

“…The C­(sp 3 )–H arylation reaction of saturated carbonyls, including ketones, aldehydes, esters, and amides, has emerged as a powerful technology in organic synthesis to increase molecular complexity through incorporation of aryl groups into the alkyl scaffolds. , While transition-metal-catalyzed α-C­(sp 3 )–H arylation reactions of carbonyls through enolate chemistry have been scrutinized and well documented, reports on the remote β-C­(sp 3 )–H bond arylation of carbonyls are much less abundant and still remain greatly challenging. − In recent years, the majority of efforts concentrated on the β-C­(sp 3 )–H arylation of carbonyls, including ketones, aldehydes, amides, carboxylic acids, and esters, using a chelation-assisted transition metal catalysis or a Pd catalysis . In contrast, remote β-C­(sp 3 )–H arylation reactions of simple ketones remain underdeveloped. − A breakthrough strategy that comprises combining Ir­(ppy) 3 photoredox and enamine catalysis enabled β-arylation of cyclic ketones with electron-deficient arylnitriles (ArCN) as the aryl source . Dong and Huang have established a new Pd­(II)-catalyzed direct oxidative β-C­(sp 3 )–H arylation of simple ketones (such as cyclic ketones and linear ketones) with aryl halides through ketone oxidative α,β -dehydrogenation, aryl halide activation, conjugate addition, and protonation cascades for the synthesis of β-monoaryl-substituted unsaturated ketones (Scheme a up) .…”

“…Dong and Huang have established a new Pd­(II)-catalyzed direct oxidative β-C­(sp 3 )–H arylation of simple ketones (such as cyclic ketones and linear ketones) with aryl halides through ketone oxidative α,β -dehydrogenation, aryl halide activation, conjugate addition, and protonation cascades for the synthesis of β-monoaryl-substituted unsaturated ketones (Scheme a up) . Despite impressive advances in the Pd­(II) oxidative catalysis enabled ketone β-arylation involving the use of various aryl resources and/or oxidants, these reactions require stoichiometric oxidants and thus may result in the diffculty to accommodate substrates that are sensitive to oxidants . Cheng and co-workers have developed a Pd(0) redox-neutral catalysis strategy, enabling dehydrogenative β-arylation of simple saturated carbonyls with aryl halides to assemble diverse α,β -unsaturated carbonyl compounds (Scheme a down) .…”

“…The plausible mechanism for this β-C­(sp 3 )–H arylation protocol was proposed (Scheme ). ,− Oxidative addition of aryl iodide 2 with the active Pd(0)­L n species A readily occurs to form ArPd­(II)­L n I intermediate B , followed by addition across the CC bond of ether 1 and desilylation by a base to afford alkylPd­(II)­L n Ar intermediate C . Dehydrogenation of the intermediate C and then coordination with the intermediate B deliver the alkene-complexed Pd intermediate D and ArPd­(II)­L n H species E .…”