Rhodium(III)‐Catalyzed Redox‐Neutral CH Annulation of Arylnitrones and Alkynes for the Synthesis of Indole Derivatives

Abstract

By using an itrone as the oxidizing directing group,amild, practical and efficientr hodium(III)-catalyzed C À Hf unctionalization for the synthesis of indole derivatives hasb een developed. This reactiono bviates the need for an externalo xidant and showsg ood functional group tolerance. Thee mployment of as terically hinderedM es group on the carbon center of the nitrone is crucial to produce indoles in high yield.

Recent Progress in the Transition Metal Catalyzed Synthesis of Indoles

“…contrast to a similar rhodium-catalyzed indole synthesis, which was non-regioselective with diarylalkynes and low-yielding with alkylarylalkynes [20]. However, it should be noted that dialkylsubstituted alkynes delivered a 3,3-disubstituted indoline.…”

“…Another common feature was the chance of scaling up the reactions without significant yield modification.Cobalt(III) catalysis often needs an oxidative directing group, but also a redox-neutral directing group has been found effective in the reaction.Among oxidative directing groups, Ackermann reported the reaction of nitrones and alkynes (Scheme 2) [19]. This reaction allowed the annulation of unsymmetrically substituted alkynes in contrast to a similar rhodium-catalyzed indole synthesis, which was non-regioselective with Catalysts 2018, 8, 458 3 of 64 diarylalkynes and low-yielding with alkylarylalkynes [20]. However, it should be noted that dialkyl-substituted alkynes delivered a 3,3-disubstituted indoline.…”

“…The authors carried out some experiments, which allowed proposing the mechanism depicted in the scheme. Catalysts 2018, 8, x FOR PEER REVIEW 3 of 64contrast to a similar rhodium-catalyzed indole synthesis, which was non-regioselective with diarylalkynes and low-yielding with alkylarylalkynes [20]. However, it should be noted that dialkylsubstituted alkynes delivered a 3,3-disubstituted indoline.…”

Nitrone Directing Groups in Rhodium(III)‐Catalyzed C−H Activation of Arenes: 1,3‐Dipoles versus Traceless Directing Groups

“…In 2013 we reported the first catalytic CÀH activation of nitrones. [5] Later, we and others realized their couplings with alkenes, alkynes, diazo compounds, and arenes under redox-neutral conditions, [6] where the role of the nitrone is limited to its oxidizing or electrophilic properties in post-coupling transformations.…”

Reaching Green: Heterocycle Synthesis by Transition Metal‐Catalyzed C−H Functionalization in Sustainable Medium

“…[33] Later,L u's group developed another methodf or indole synthesis from arylnitrones 24 and alkynes through Rh-catalyzed CÀHa ctivation. [34] The reaction delivered av ariety of indole derivatives in as ustainable reaction medium, however,i tp roduced as toichiometric amount of mesityl aldehyde as the by-product.…”