Recent Advances in the Construction of Polycyclic Compounds by Palladium‐Catalyzed Atom‐Economical Cascade Reactions

Abstract

The development of cascade reactions that realize step-economical syntheses of complex compounds by multiple bond formation is one of the most attractive subjects in modern organic chemistry. Another important challenge in this area is to improve atom economy by minimizing waste product formation and avoiding prefunctionalization of the substrates. Because palladium catalysts are well known to promote a variety of atom-economical elementary reactions, many useful palladium-catalyzed cascade reactions have been developed. In this Focus Review, recent advances in palladium-catalyzed atom-economical cascade reactions for the construction of polycyclic compounds are summarized. Especially, the cascade reactions reported in the past decade, which include carbopalladation onto alkyne/alkene/allenes, nucleophilic reaction, and direct arylation/C À H bond functionalization, are highlighted.

Nickel‐CatalyzedDicarbofunctionalization of Alkenes†

“…[ 1‐7 ] Among the developed methods, transition metal‐catalyzed difunctionalization of alkenes enables preparation of complex molecules from simple available alkenes by diversifying the C=C double bond with high atom‐ and step‐economic efficiency. [ 8‐21 ] In particular, the dicarbofunctionalization of alkenes has gained special attention because it can construct complex carbon skeletons by assembling two carbon entities across the C=C bond and forming two C—C bonds in an one‐pot reaction (Scheme 1). [ 22‐25 ] Over the past decade, considerable efforts have been devoted to this area and impressive progress has been achieved.…”

Tandem Pd-Catalyzed Cyclization/Coupling of Non-Terminal Acetylenic Activated Methylenes with (Hetero)Aryl Bromides

“…Steric hindrance caused by shift of a substituent to the ortho position seemed to have little influence on the overall efficiency of the process (9 and 10). Various functional groups, including amides, ketones, and aldehydes were well tolerated (7)(8)(9)(10)14). Moreover, a range of heteroaryl bromides, including medicinally relevant N-heterocycles, were competent reaction partners, generally delivering products 14-24 in very good yields.…”

“…Cyclization of alkynes and alkenes bearing a tethered nucleophilic group constitutes a direct and effective strategy for the construction of a range of carbo-and heterocyclic scaffolds [1][2][3][4][5][6][7][8][9][10]. Since the seminal work by Conia [11,12] on thermal cyclization of unsaturated carbonyl compounds, a range of catalytic methods towards carbocyclic motifs, featuring excellent atom economy and high efficiency under mild conditions were developed (Scheme 1a) [13].…”

Enantioselective Synthesis of Tetrahydropyrano[3,4‐b]indoles: Palladium(II)‐Catalyzed Aminopalladation/1,4‐Addition Sequence

“…[5] Among the developed cascade reactions,t ransition-metal-catalyzed transformations have proved to be powerful methods for the synthesis of either cyclic or acyclic compounds from relatively simple starting materials in as tepwise way. [7] In light of our interest in the use of palladium(II) catalysts for domino reactions in aredox-neutral way and our recently reported works on successful synthesis of some nitrogen-and oxygen-containing heterocycles, [8] we want to prepare 1,3,4,9-tetrahydropyrano [3,4-b]-indoles by using aniline-tethered alkynyl cyclohexadienones as the substrates. [7] In light of our interest in the use of palladium(II) catalysts for domino reactions in aredox-neutral way and our recently reported works on successful synthesis of some nitrogen-and oxygen-containing heterocycles, [8] we want to prepare 1,3,4,9-tetrahydropyrano [3,4-b]-indoles by using aniline-tethered alkynyl cyclohexadienones as the substrates.…”

“…[6] Particularly,p alladium-catalyzed tandem cyclizations,c onstituting an important synthetic route to complex heterocyclic compounds,have captured much attention. [7] In light of our interest in the use of palladium(II) catalysts for domino reactions in aredox-neutral way and our recently reported works on successful synthesis of some nitrogen-and oxygen-containing heterocycles, [8] we want to prepare 1,3,4,9-tetrahydropyrano[3,4-b]-indoles by using aniline-tethered alkynyl cyclohexadienones as the substrates. This tandem cyclization would be initiated by intramolecular aminopalladation of alkynes and quenched by addition to the intramolecular cyclohexenone (Scheme 1c).…”