ABSTRACT. A novel four-step domino process for the synthesis of 3-[2-(aryl/alkylsulfonyl)ethyl]indoles starting from readily available 2-iodoanilines is reported. The domino reaction is based on the intramolecular palladium-catalyzed α-arylation of sulfones, which was combined with both intermolecular aza-Michael and Michael addition reactions using vinyl sulfones as the electrophile. The domino process produced good yields and tolerated the presence of substituents with different electronic properties on the aniline ring. In addition, Density Functional Theory (DFT) calculations were carried out to gain more insight into the formation of the observed indole derivatives.
The intramolecular carbene C–H insertion of α‐diazo‐α‐(methoxycarbonyl)acetamides leading to β‐lactams is effectively catalyzed by palladium complexes. It is found that although Pd0 catalysts typically produce mixtures of β‐lactams together with Buchner‐type reaction products, the use of PdII catalysts results in highly chemoselective transformations. According to DFT calculations, this insertion reaction occurs stepwise and involves an unprecedented PdII‐promoted Mannich‐type reaction through a metallacarbene‐induced zwitterionic intermediate.
A new strategy for the synthesis of tetrahydroisoquinolines based on the Pd(0)-catalyzed intramolecular α-arylation of sulfones is reported. The combination of this Pd-catalyzed reaction with intermolecular Michael and aza-Michael reactions allows the development of two- and three-step domino processes to synthesize diversely functionalized scaffolds from readily available starting materials.
Sulfonates, sulfonamides, and phosphonates have proven useful nucleophiles for palladium‐catalyzed intramolecular α‐arylation reactions leading to tetrahydroisoquinolines. Although the sulfonate α‐arylation reaction can be successfully combined in a domino process with a broad range of Michael acceptors, only vinyl sulfones can be used in Michael additions when starting from sulfonamides. No domino process was developed with the phosphonate derivative. DFT calculations were carried out to gain more insights into the experimental differences observed in the reactions involving these substrates.
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