Tunable Pd-Catalyzed Cyclization of Indole-2-carboxylic Acid Allenamides: Carboamination vs Microwave-Assisted Hydroamination

Abstract

A variety of 3-vinyl-substituted imidazo[1,5-a]indole derivatives were synthesized by intramolecular Pd-catalyzed cyclization of the title allenamides through either a domino carbopalladation/exo-cyclization process or a novel hydroamination reaction that proceeds smoothly under microwave irradiation. Both the observed pathways involve a π-allyl-palladium(II) complex arising from insertion of the allene group into a palladium(II) species, the latter being formed in situ by the intervention of an aryl iodide or of the N-H group. In both cases, the role of nucleophile is covered by the indole nitrogen.

Transition‐Metal‐Catalyzed Hydroamination Reactions

“…This early result pointed toward the application of gold-catalyzed allene hydroamination with both protected and unprotected amines for the synthesis of more complex heterocyclic target compounds [226][227][228]. These aspects will be highlighted in Section 15.4.4.…”

Allenamides: A Powerful and Versatile Building Block in Organic Synthesis

“…Broggini 66 further developed their carboamination and microwave-assisted hydroamination work using allenamides 192 that contains an indolyl unit (Scheme 56). Using 192 , Styryl-substituted indoloimidazoles derivatives 194 were synthesized through the intermediacy of palladium π-allyl complex 193 in which the trapping exclusively occurred at the internal allenic carbon by the indole nitrogen.…”

Gold‐ or Palladium‐Catalyzed Allene Carbocyclization/Functionalization: Simple and Efficient Synthesis of Carbazoles

“…[7] On the other hand, despite the rich chemistry of palladium, [8,9] the Pd-catalyzed cyclizations of indole-tethered allenes find rare precedents in the literature; only Broggini has recently reported the N-cyclization of indole-2-carboxylic acid allenamides. [10] A process which involves a selective chemical reaction, even if the structure of the substrate suggests numerous possibilities for reactivity, represents an attractive strategy. [11] NH-Indole-tethered allenols have diverse reactive sites, at which different transformations (C-cyclization versus O-cyclization versus N-cy-A C H T U N G T R E N N U N G clization) can take place.…”