Synthesis of Unprotected Indoles

The classical Fischer indole synthesis has persisted as a commonly used procedure due to its working simplicity. However, this method suffers some drawbacks, such as the need for strong acids, poor selectivity with unsymmetrical ketones, and poor functional group tolerance. Huang et al. developed an alternative synthetic strategy for the synthesis of unprotected indoles a tandem ortho-C-H activation and annulation by using triazenyl arenes and alkynes. This reaction involves a ring contraction by a 1,2-Rh shift and an N=N insertion (Eq. (5.12)) 

A highly regioselective protocol was reported that delivered numerous 3,4-disubstituted indole derivatives with excellent yields by hydrazine-directed Rh-catalyzed C-H activation, in which the protected hydrazine acts as a directing group and as an internal oxidant (Eq. (5.14)) [11a]. The reaction was promoted by an acetic acid additive. Similarly, a Rh(IIl)-catalyzed reaction of an arylhydrazine salt, a diethyl ketone, and an alkyne to synthesize a 3,4-disubstituted indole was also reported by our group. The reaction proceeds by in situ condensation of an arylhydrazine with diethyl ketone to form an arylhydrazone intermediate (Eq. (5.15)) [11b]. 

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