Indole synthesis by a gold(I)-catalyzed intermolecular formal [4+2] reaction between 1,3-diynes and pyrroles has been developed. This reaction involves the hydroarylation of 1,3-diynes with pyrroles followed by an intramolecular hydroarylation to give the 4,7-disubstituted indoles. This reaction can also be applied to the synthesis of carbazoles when indoles are used as the nucleophiles instead of pyrroles.

New and interesting polycyclic compounds have been synthesized from non-conjugated diyne systems by dual gold catalysis. A quaternary carbon center in the backbone and the accompanying Thorpe–Ingold effect enabled the unprecedented insertion of sp³ and sp² CH bonds that for the first time were incorporated within the backbone of the diyne system and allowed the construction of complex polycyclic carbon scaffolds inaccessible by previous approaches in which the CH bonds for the insertion were situated at the other end of the alkyne.

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/CH bond functionalization, are highlighted.

The development of cascade reactions is an area of considerable interest in modern organic chemistry. Efficient cascade reactions realize the economical synthesis of complex target molecules through multiple bond formations in a single operation. Elementary reactions that form fewer waste products are desirable in terms of atom economy and in order to suppress side product formation in sequential processes. Recent advances in homogeneous gold catalysis have opened up further possibilities for cascade reactions. In this review, recent advances in gold-catalyzed cascade cyclizations of alkynes are summarized. In particular, cascade reactions based on nucleophilic/electrophilic addition, carbene cyclopropanation/insertion, ring expansion, and cycloaddition are highlighted. Notably, many of the cascade reactions shown in this mini-review feature no theoretical waste products.

The total synthesis of the pentacyclic tetrahydroisoquinoline alkaloid quinocarcin, which possesses intriguing structural and biological features, has been achieved through a gold(I)-catalyzed regioselective hydroamination reaction. It is noteworthy that the regioselectivity of the intramolecular hydroamination of an unsymmetrical alkyne could be completely switched through substrate control. Other key features of this synthesis include the highly stereoselective synthesis of 2,5-cis-pyrrolidine through the intramolecular amination of the bromoallene and the Lewis acid mediated ring opening of dihydrobenzofuran.

Palladium-catalyzed cascade CH alkenylation and arylation provides convenient access to polycyclic aromatic compounds. Treatment of 3-bromoaniline derivatives bearing a bromocinnamyl group on the nitrogen atom with a catalytic amount of [Pd(OAc)₂] and PCy₃⋅HBF₄ in the presence of Cs₂CO₃ in dioxane affords naphthalene-fused indole derivatives in good yields. This double cyclization reaction is also applicable to heterocyclic substrates, giving fused indoles containing a heteroaromatic ring such as dibenzofuran, dibenzothiophene, carbazole, indole, or benzofuran through heterocyclic CH arylation. When using a 2,6-unsubstituted aniline derivative, the first CH arylation preferentially proceeds at the more hindered position of the aniline ring.

Aniline-substituted diethynylarenes, which are readily synthesized through Sonogashira coupling reactions from commercially available 1,2-dihaloarenes, directly produce aryl- and heteroaryl-annulated[a]carbazoles by the gold-catalyzed intramolecular cascade hydroamination/cycloisomerization without producing theoretical by-products. This new atom-economical route is easily applicable to various aryl-annulated[a]carbazoles containing an alkyl, aryl or ester substituent.

The palladium(0)-catalyzed direct construction of bicyclic heterocycles is described. Treatment of propargyl bromides that have nucleophilic functional groups connected by two or three carbon atoms with catalytic [Pd(PPh₃)₄] affords bis-cyclization products in good yields. The desired bicyclic heterocycles can be obtained selectively when using substrates with appropriate nucleophilic groups. We also describe the reaction of a 2-alkynylazetidine derivative with a catalytic amount of [Pd(PPh₃)₄] under base-free conditions, which affords the same fused heterocycles as the corresponding propargyl bromides.

Structually related to the known CK2 inhibitors, 2,6-disubstituted pyrazine and 4,6-disubstituted pyrimidine derivatives were synthesized and their inhibitory activities toward CK2α and CK2α′ were evaluated. Structure-activity relationship study has revealed that several pyrazine derivatives bearing a (pyrrol-3-yl)acetic acid and a monosubstituted aniline possess potent inhibitory activities.