Palladium-free zinc-mediated hydroamination of alkynes: efficient synthesis of indoles from 2-akynylaniline derivatives

Transition‐Metal‐Catalyzed Hydroamination Reactions

“…By exploiting the known formation of indole from σ-ethynylaniline, Okuma was able to realize this Lewis-acid-mediated transformation with simple Zn 2+ salts (Scheme 15.109). Interestingly, in a one-pot reaction, σ-nitro-substituted phenylalkynes could be used as substrates whereby Zn metal is first used to reduce the nitro group and then the Zn salts formed in situ mediate the subsequent hydroamination for indole formation [345]. As o-substituted aniline starting materials are commonly applied in indole synthesis and can be used in combination with a broad range of catalysts, Messerle and coworkers [346] showed that this transformation provided the basis for a highthroughput screening approach in catalyst discovery.…”

A Reusable MOF‐Supported Single‐Site Zinc(II) Catalyst for Efficient Intramolecular Hydroamination of o‐Alkynylanilines

“…Both higher and lower amounts of toluene had ad eleterious effect (entries 4, 5, and 10), which might be because the solvent impacted the diffusion and concentration of both substrate and product. This observation shows indirectly that the cycloisomerization reaction was catalyzed by unsaturated Lewis acidic Zn II sites inside the MOFs.R eaction conditions similar to those used with Zn-UiO-67-BPY were established in ah omogeneous catalytic system (Table S1, entries [19][20][21][22][23][24][25][26] and unexpectedly,t he main product was 1-(2-aminophenyl)-2-phenylethanone (3a)i n 73 %-86 %y ield (Table S1, entries 19 and 23), which corresponds to the hydration of the alkyne to construct acarbonyl motif. To further understand the cycloisomerization reaction, control experiments were conducted (Table S1).…”

Zinc reagents as non-noble catalysts for alkyne activation

“…23 Later, Okuma and co-workers showed that zinc halides were also effective catalysts for this transformation. 24 Scheme 5. Zinc-catalyzed synthesis of indole 26 via intramolecular hydroamination.…”