Metal-Catalyzed Cascade Reactions between Alkynoic Acids and Dinucleophiles: A Review

Abstract

Cascade reactions provide a straightforward access to many valuable compounds and reduce considerably the number of steps of a synthetic sequence. Among the domino and multicomponent processes that involve alkynes, the cascade reaction between alkynoic acids and C-, N-, O- and S-aminonucleophiles stands out as a particularly powerful tool for the one-pot construction of libraries of nitrogen-containing heterocyclic compounds with scaffold diversity and molecular complexity. This reaction, based on an initial metal-catalyzed cycloisomerization that generates an alkylidene lactone intermediate, was originally catalyzed by gold(I) catalysts, along with silver salts or Brönsted acid additives, but other alternative metal catalysts have emerged in the last decade as well as different reaction media. This review examines the existing literature on the topic of metal-catalyzed cascade reactions of acetylenic acids and dinucleophiles and discusses aspects concerning substrate/catalyst ratio for every catalyst system, nature of the aminonucleophile involved and substrate scope. In addition, alternative solvents are also considered, and an insight into the pathway of the reaction and possible intermediates is also provided.

New Avenues for the Synthesis of Oxa‐Cycles Using Lewis/Brønsted Acid Mediated Carboxygenation and Carboalkoxylation of Alkynes

“…Given the importance of alkyne-carboxygenation and carboalkoxylation, several reviews have appeared involving transition metal-catalyzed CÀ C and CÀ O bond-forming reactions. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] However, generation of bio-hazardous waste, and metallic by-products were the longstanding problem in these types of reactions. To circumvent these deficiencies, various transition metal-free strategies exhibiting cascade functionalization of alkynes have been also reported in the literature.…”

“…Given the importance of alkyne‐carboxygenation and carboalkoxylation, several reviews have appeared involving transition metal‐catalyzed C−C and C−O bond‐forming reactions [12–26] . However, generation of bio‐hazardous waste, and metallic by‐products were the longstanding problem in these types of reactions.…”

Transition metal catalysed cascade C–C and C–O bond forming events of alkynes

“…In addition to this significant utility of cascade processes in synthetic methodologies, these processes have been extensively used in the stereoselective and enantioselective total synthesis of complex natural products. [1][2][3][4][5][6][7][8][9][10] Alternatively, the existing dual nature (electrophilic and nucleophilic properties) of alkynes in a suitable reaction environment has made them valued synthons, and thus, alkynes have attracted significant attraction from the synthetic…”

Total Synthesis of Strigolactones via Palladium-Catalyzed Cascade Carbonylative Carbocyclization of Enallenes

“…The reaction of dissymmetric substrate 4k (R 1 = H, and R 2 = CHMe 2 ) produced two products, 3ka On the basis of the cascade reactions depicted in Scheme 2, we developed a one-pot process involving Pd-catalyzed carbonylative carbocyclization and elimination of TsOH from the tosylated product in the presence of Et 3 N to afford cyclopentenone 3m (in 63% yield) and 3n (in 84% yield), which could serve as useful intermediates for the synthetic route to SLs (Scheme 3). Kinetic isotope effect studies suggest that the formation of Int-1 (Scheme 1B), involving C(sp 3 )−H be the ratedetermining step (RDS) (cf. the Supporting Information for a detailed discussion).…”

“…Cascade reactions in organic synthesis are challenging and innovative but require delicate retrosynthetic strategies. − In addition to their aesthetic appeal, cascade processes offer economical and environmentally friendly means for generating molecular complexity. , Consequently, these reactions have found numerous applications in the synthesis of complex molecules, both natural and designed. Utilizing cascade reactions in the synthesis of natural products can be highly efficient and may produce remarkable outcomes. , …”