Annulation of internal alkynes through a hydroamination/aza-Heck reaction sequence for the regioselective synthesis of indoles

Domino CN Coupling/Annulation versus CN Coupling/ Hydroamination of 2‐Alkynyl‐3‐bromobenzothiophenes and 2‐Alkynyl‐3‐bromothiophenes. Highly Efficient Synthesis of Benzothieno[3,2‐b]quinolines and Thieno[3,2‐b]pyrroles

“…Buchwald and co-workers showed that (copper-catalyzed) domino C À N coupling/hydroamination reactions proceed with the C À N coupling as the first step. [7] Therefore, we believe that this is the case also in our transformation. While the C À N coupling must proceed by palladium catalysis, the subsequent annulation may proceed either by a palladium-catalyzed or by a thermal process.…”

“…[6] Ackermann et al reported the synthesis of indoles and various other ring systems by domino Narylation/hydroamination reactions. [7] They also developed an efficient approach to indoles by Pd-or Cucatalyzed domino C À N coupling/hydroamination reactions of ortho-alkynylated aryl halides. [8] Buchwald et al reported the synthesis of pyrroles and pyrazoles by a related strategy.…”

“…As mentioned above, Buchwald and co-workers reported the synthesis of thienopyrroles by copper-catalyzed domino C À N coupling/hydroamination reaction of 2-alkynyl-3-bromothiophenes with (BOC)NH 2 . [7] On the one hand, annulation reactions are, of course, only possible for anilines, but not for alkylamines or (BOC)NH 2 . On the other hand, the different chemical behaviour of 2-alkynyl-3-bromobenzothiophenes and 2-alkynyl-3-bromothiophenes in their reaction with anilines is surprising.…”

Transition‐Metal‐Catalyzed Hydroamination Reactions

“…Approaches for indole synthesis using hydroamination as a key step in their syntheses has been an ongoing area of investigation over the past several years [329,330]. Early examples focused on one-pot intermolecular hydrohydrazination followed by the Lewis-acid-catalyzed Fischer indole synthesis [331,332] (Scheme 15.102) or one-pot intermolecular hydroamination followed by cross-coupling to either form a C-N bond (via the Buchwald-Hartwig amination) [333] (Scheme 15.103) or a C-C bond (via a Heck reaction) [334,335] (Scheme 15.104). Alternatively, σ-alkynylanilines can be used directly as substrates for intramolecular hydroamination (Scheme 15.105) [198,200,[336][337][338][339][340].…”

Titanium Reagents in Heterocyclic Synthesis

“…2-chlorophenyl substituted enamine is formed in one-pot procedure (Scheme 3). [13] Unsymmetric al substituted alkynes enable the synthesis of diversely functionalized indoles with regioselectivity. However, more selective anti-Markovnikov hydration of internal and terminal alkynes was attained using more sterically hindered amines.…”