Regioselective synthesis of tetrahydroquinolines via syn- and anti-nucleopalladation-initiated cascade processes.

Palladium(ii)-catalyzed regioselective syn-chloropalladation and anti-acetoxypalladation-initiated cascade processes were developed for the synthesis of functionalized tetrahydroquinolines. A series of N-propargyl arylamines tethered with an α,β-unsaturated carbonyl scaffold underwent atom economical cascade reactions to deliver chloro- and acetoxy-substituted tetrahydroquinolines bearing an exocyclic double bond in high yields. A mechanism is proposed for these cascade processes involving a sequential syn-chloropalladation or anti-acetoxypalladation of alkynes followed by intramolecular olefin insertion (6-exo-trig) and protonolysis steps.

Direct Access to 9-Chloro-1-benzo[]furo[3,4-]azepin-1-ones via Palladium(II)-Catalyzed Intramolecular -Oxypalladation/Olefin Insertion/sp-C-H Bond Activation Cascade.

An efficient Pd(II)-catalyzed cascade approach was established for the synthesis of 9-chloro-1-benzo[]furo[3,4-]azepin-1-ones starting from -propargyl arylamines having a pendant α,β-unsaturated ester scaffold. The mechanism of this sequential process involved intramolecular -oxypalladation followed by olefin insertion and sp-C-Cl bond formation reactions. This high atom- and step-economical cascade sequence generated two heterocycle rings and three new bonds in a single synthetic operation.

Palladium-Catalyzed Regioselective Syn-Chloropalladation-Olefin Insertion-Oxidative Chlorination Cascade: Synthesis of Dichlorinated Tetrahydroquinolines.

A palladium catalyzed cascade process involving syn-chloropalladation, intramolecular olefin insertion, and oxidative C-Cl bond formation reactions was demonstrated for the synthesis of dichlorinated tetrahydroquinolines in high yields (up to 93%). The N-propargyl arylamines having a tethered α,β-unsaturated carbonyl moiety underwent a regioselective syn-chloropalladation followed by a Heck-type reaction to deliver the tetrahydroquinoline scaffold. The rare insertion of the second chlorine atom was rationalized comprising a Pd catalytic cycle and oxidative cleavage of the C-Pd bond.

Synthesis, Characterization, and Biomedical Applications of an Alkylated Quercetin-Gadolinium Complex.

Flavonoids and their derivatives have been extensively studied for their pharmaceutical applications due to their antioxidant and anti-inflammatory properties. The coordination complexes of several flavonoids have demonstrated DNA binding ability that can confer anticancer properties. The structure of the flavonoid has a pronounced influence on its pharmacological properties.

Palladium-Catalyzed Internal Nucleophile-Assisted Hydration-Olefin Insertion Cascade: Diastereoselective Synthesis of 2,3-Dihydro-1H-inden-1-ones.

A novel palladium-catalyzed hydration-olefin insertion cascade assisted by internal nucleophiles was developed for the synthesis of biologically significant 2,3-dihydro-1H-inden-1-ones under mild conditions. A detailed mechanistic study revealed that the assistance of the internal nucleophiles is crucial to trigger the cascade reaction via nucleopalladation of the alkyne moiety. The overall reaction is equivalent to regioselective hydration of alkynes followed by intramolecular Michael addition.

Synthesis of 5,6-Dihydrodibenzo[b,h][1,6]naphthyridines via Copper Bromide Catalyzed Intramolecular [4 + 2] Hetero-Diels-Alder Reactions.

A highly efficient synthesis of 5,6-dihydrodibenzo[b,h][1,6]naphthyridines was achieved by reaction between 2-(N-propargylamino)benzaldehydes and arylamines in the presence of CuBr2. The in situ generated electron-deficient heterodienes bearing a tethered alkyne partner underwent an intramolecular inverse electron-demand hetero-Diels-Alder reaction followed by air oxidation to furnish the products in high yields. This reaction tolerated a large number of substituents to afford diverse products under mild conditions.

Palladium(II)-catalyzed intramolecular carboxypalladation-olefin insertion cascade: direct access to indeno[1,2-b]furan-2-ones.

A catalytic, atom-economical, domino 5-endo-dig cyclization-intramolecular olefin insertion sequence was developed under mild conditions. Aryl alkynoic acids bearing a tethered enone partner afforded the indeno[1,2-b]furan-2-ones, the core skeleton present in a number of biologically significant molecules including the natural product solanacol, under ligand-free, palladium-catalyzed reaction conditions in high yields. The competitive β-hydride elimination in the final step leading to the conjugated analogs was avoided by the addition of lithium bromide.