Copper(I) substitutions. Scope and mechanism of cuprous acetylide substitutions

Transition Metal‐Catalyzed Synthesis of Fused Five‐Membered Aromatic Heterocycles

“…Castro first documented cycloisomerization of ortho-alkynylanilines 96 to give the 2-phenyl indole 97 in the presence of substoichiometric amounts of Cu(I) catalyst in excellent yield (Scheme 9.35) [77,111]. Mechanistically, it is believed that 5-exo-dig cyclization follows the generally accepted mechanism proposed for an intramolecular addition of various nucleophilic entities to transition metal-activated carboncarbon multiple bonds.…”

“…Hence, recent contributions to these methods are discussed in detail below. The synthesis of benzofurans and related compounds from ortho-iodophenol and copper(I) acetylides via a coupling-cyclization reaction (vide infra) was introduced by Castro in the 1960s [75][76][77] and stimulated the development of many contemporary transition metal-catalyzed synthetic approaches toward the assembly of the benzofuran unit. In a subsequent report from Castros group, it was proposed that the formation of the benzofuran core occurs in a stepwise fashion with the intermediacy of ortho-alkynylphenol, which, upon activation by the Cu(I) salt promoter, undergoes subsequent cycloisomerization [77].…”

“…According to the proposed mechanism, the reaction begins with the exchange process between the alkynyl silane 47 and the Cu(I)-catalyst to generate the copper(I) acetylide 49. In parallel, a more Lewis- [75][76][77]111]. It was proposed that the formation of the benzofuran 57 is a stepwise reaction involving formation of the ortho-alkynylphenol intermediate 56 [77].…”

“…In parallel, a more Lewis- [75][76][77]111]. It was proposed that the formation of the benzofuran 57 is a stepwise reaction involving formation of the ortho-alkynylphenol intermediate 56 [77]. The authors demonstrated that a variety of substituted benzofurans could be synthesized in generally high yields via this stoichiometric approach.…”

“…[75,76,111], simultaneously with the mentioned earlier coupling-cyclization reaction en route to benzofurans 57 (Scheme 9.21). It is believed that this stoichiometric in copper cascade reaction proceeded with the generation of an intermediary ortho-alkynylaniline 263 [77]. Attempts to turn this reaction into a more practical catalytic process, using basic conditions to generate Cu(I)-acetylide from a terminal alkyne in the presence of CuI, provided poor yields of the respective indoles 264.…”