Palladium Nanoparticle-Catalyzed Stereoselective Domino Synthesis of 3-Allylidene-2(3H)-oxindoles and 3-Allylidene-2(3H)-benzofuranones

Abstract

A single-step, stereoselective protocol for the synthesis of unsymmetrically substituted (E)-3-allylideneoxindole and (E)-3-allylidenebenzofuran from readily accessible starting materials using palladium binaphthyl nanoparticles (Pd-BNPs) has been developed. Pd-BNP showing a wide range of functional group tolerance and an immense array of substrate scope have been explored with the successful synthesis of the drug molecule “tubulin polymerization inhibitor” free from trace metal impurities. The model reaction is extended to a gram-scale synthesis, and one of the products is utilized for derivatization. The Pd-BNP has been recycled up to 5 catalytic cycles without any loss in reaction yields and particle size of nanoparticles.

Stereoselective Construction of Unsymmetrically Linked Heterocycles via Palladium-Catalyzed Alkyne Insertion/Cycloimidoylation Cascade

“…Next, we tested the imidoylative cyclization with N -(2-iodophenyl)­propiolamide as the electrophilic coupling partner. Unexpectedly, products 3a and 5a , rather than their E -isomers, were generated in relatively lower yields under the applied conditions through anti alkyne insertion reactions (Scheme a,b) . Suzuki and Sonogashira coupling of 3e were realized, giving products 7a and 7b in 76 and 69% yields, respectively.…”

Synthesis of Benzofused O- and N-Heterocycles through Cascade Carbopalladation/Cross-Alkylation of Alkynes Involving the C–C Cleavage of Cyclobutanols

“…The fact that propiolamide substrates afford the E- alkenylated oxindoles 3s – u as main coupling products reveals that in those cases the alkenyl-Pd­(II) intermediate, arising from the syn carbopalladation step, could undergo an isomerization process. There are several precedents in the literature of related Pd-catalyzed cascade reactions involving the syn carbopalladation of alkynes and subsequent isomerization prior to the final C–Pd bond functionalization. ,,,− Generally, the isomerization of the alkenyl-Pd intermediates is driven by steric factors. Nevertheless, α-alkyl-substituted alkynyl substrates, such as 1a , require the use of bulky phosphine ligands (Q-Phos, X-Phos, or P t Bu 3 among others) to increase the steric hindrance around the Pd center and therefore promote the isomerization. ,, In the case of α-acyl-substituted alkynyl substrates, such as propiolamides 1m – o , the isomerization is a frequent feature in a range of different conditions, probably due to the conjugation of the alkenyl-Pd moiety and the carbonyl group, which might lower the energy barrier for the C–C rotation process (Scheme ).…”

Recent Progress of Metal Nanoparticle Catalysts for C–C Bond Forming Reactions

“…Wu et al have established a cascade alkynylation and selective hydrogenation catalyzed by covalent binaphthyl-stabilized Pd NPs to provide a novel and highly efficient methodology for accessing Z and Z,Z-selective phosphinyl [3]dendralenes [374]. Binaphthylstabilized Pd NPs were also utilized to synthesize diphenylallylidenemethylindolin-2-ones, indanone derivative, 3-allylidene-2(3H)-oxindoles, and 3-allylidene-2(3H)-benzofuranones (Scheme 38) [375][376][377][378]. Obora et al found that Ir NPs showed excellent catalytic activity in β-(aryl)methylation of alcohol [379,380].…”