Palladium‐Catalyzed Heterocyclization: A Carbon‐Centered Approach

Abstract

Heterocycles are some of the most important and widely used motifs in synthetic and medicinal chemistry.I ti s therefore not surprising that the synthesis of heterocycles is ar ich area of chemical research. Catalytic heterocyclization that makes use of heteroatomic nucleophiles, such as oxygen and nitrogen, is one such powerful strategy.T his Focus Review considers an alternative approach that uses carbon-based nucleophiles that are generated during palladium-catalyzed heterocyclization reactions. This complimentary method allows accesst oar ange of useful and otherwise-inaccessible targets. Occurring throughar ange of different mechanisms, the utility of this approach can be seen in the wide range of transformations that can be undertaken, along with its repeated application in the synthesis of complex molecules.

Syntheses of 3,3-Disubstituted Dihydrobenzofurans, Indolines, Indolinones and Isochromanes by Palladium-Catalyzed Tandem Reaction Using Pd(PPh3)2Cl2/(±)-BINAP as a Catalytic System

“…Compound V exhibits selective 5-hydroxytryptamine7 (5-HT 7 ) antagonist activity (K i = 0.79 nm) [13] and alstonisine (VI) also reveals antiplasmodial activity against Plasmodium falciparum, with an IC50 (half maximal inhibitory concentration) of 7.6 µM [14] (Figure 1). Therefore, organic chemists around the world made extensive efforts to develop the highly efficient methods of constructing these heterocycles [15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Of these molecules, 3,3-disubsitituted five-membered chemists around the world made extensive efforts to develop the highly efficient methods of constructing these heterocycles [15][16][17][18][19][20][21][22][23][24][25][26][27][28].…”

“…The domino reactions of the synthesis of them were summarized mainly as follows: (i) the Pd or Ni-catalyzed cyclocarbopalladation/coupling fractions, in which the process was initiated by Heck cyclization of a starter (halide) and a relay (alkene), followed by intermolecular coupling reactions with a terminator (organometallic reagents, alkenes, alkynes, etc. ), including Suzuki, Stille, Heck, Sonogashira, C-H activation, carbonylation and amination and so forth [15][16][17]22,24,25,[29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44]; (ii) the C-H oxidative radical coupling reactions, in which these transformations were based on tandem radical addition/cyclization in the presence of oxidants with/without metal catalysts [18][19][20][21]23,26,[45][46][47][48][49][50][51][52][53][54][55]; and (iii) the other reactions [24,[56][57][58][5...…”

Recent Advances in Phthalan and Coumaran Chemistry

“…To the best of our knowledge, the last two comprehensive reviews concerning coumaran synthesis were published in 2009 and 2011 . The most recent review focuses on palladium‐catalyzed cyclization to yield various heterocyclic systems, including coumarans, but does not discuss alternative preparatory routes.…”

Synthesis of 3,3-Disubstituted Heterocycles by Pd-Catalyzed Arylallylation of Unactivated Alkenes

“…3 A lesser-used set of reactions utilizes starting materials where the carbon–heteroatom bonds are already in place. 4 For example, Pd-promoted cyclization of aryl bromide 3 , followed by Sonogashira–type coupling affords oxindole 4 (Figure 1b). 5…”