Palladium‐Catalyzed Double Cyclization Processes Leading to Polycyclic Heterocycles: Recent Advances

Abstract

In this minireview, we discuss some recently reported methods for the synthesis of polycyclic heterocycles by palladium‐catalyzed double cyclization processes. Paradigmatic examples taken by the most recent literature (from 2014 to the beginning of 2019) are presented. Only transformations in which palladium is involved in at least one cyclization stage are taken into consideration. The first part deals will Pd(0)‐catalyzed processes. Double cyclizations initiated by the oxidative addition of an Ar–X bond or other functional groups are treated first, followed by processes beginning with carbopalladation by Pd(0) attack to unsaturated bonds. The second part concerns Pd(II)‐catalyzed reactions, and begins with double cyclizations initiated by intramolecular nucleophilic attack to unsaturated bonds coordinated to Pd(II), followed by processes initiated by aromatic palladation.

Site-Selective Double and Tetracyclization Routes to Fused Polyheterocyclic Structures by Pd-Catalyzed Carbonylation Reactions

“…We have recently reported efficient palladium-catalyzed syntheses of indole-fused furanones and furofuranone derivatives as examples of successful carbonylative cascade double-cyclization processes from easy accessible multifunctional precursors to complex molecular structures . In particular, anilines bearing propargyl alcohol moieties in the ortho position delivered a variety of polycyclic furo­[3,4- b ]­indol-1-ones through a sequence of indolization ( I-1 ), carbonylation ( I-2 ), and lactonization reactions in the presence of PdI 2 /KI as a stable and highly efficient catalytic system (Scheme a) .…”

Isoindolinone Synthesis via One‐Pot Type Transition Metal Catalyzed C−C Bond Forming Reactions

“…During the past decade, av arietyo fc atalytic methodologies have been investigated in order to minimize the number of reaction steps and to maximize the directutilization of commercially availablec ompounds fort he synthesis of isoindolinone based structures. [17] Especially transition-metal catalyzed CÀCb ond formation with subsequent lactamization have provided simplified access to al arge variety of isoindolinone derivatives. These reactions involve the use of CÀHa ctivation, carbonylation, cross-coupling, addition, condensation, formal cycloaddition and annulation based strategies.…”

A Zinc-Mediated Deprotective Annulation Approach to New Polycyclic Heterocycles

“…The development of efficient methods for the synthesis of high value added polycyclic heterocyclic derivatives by metal-promoted annulation of acyclic precursors is one of the most important area of research in heterocyclic chemistry [ 1 , 2 , 3 , 4 , 5 ]. Polycyclic heterocyclic systems, in fact, are largely present as fundamental cores in natural products and in biologically active compounds [ 6 , 7 , 8 , 9 , 10 , 11 ], and the possibility to obtain them by a simple cyclization process starting from readily available substrates is particularly attractive [ 1 , 2 , 3 , 4 , 5 ].…”

“…Among acyclic substrates able to undergo a metal-promoted cyclization to give a polycyclic heterocycle, functionalized alkynes bearing a suitably placed heteronucleophile play a major role, as the triple bond can be easily electrophilically activated by a suitable metal species thus promoting the cyclization by intramolecular nucleophilic attack [ 1 , 2 , 3 , 4 , 5 ]. Usually, processes like these are promoted by costly metals (mainly gold [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ], palladium [ 20 , 21 , 22 , 23 ], rhodium [ 24 , 25 , 26 ], platinum [ 27 , 28 , 29 ], and, occasionally, ruthenium [ 30 ]), while the use of less expensive metal species, such as cobalt [ 31 ], nickel [ 32 ], copper [ 33 , 34 , 35 , 36 ], zinc [ 37 , 38 , 39 , 40 ], and silver [ 41 , 42 ] compounds, has been scantly reported in the literature, and applied to a limited number of examples.…”