Hemetsberger Indole Synthesis

The Hemetsberger indole synthesis involves the thermolysis of α-azidocinnamate esters in xylene to give the corresponding indole-2-carboxylates via nitrene intermediates. The starting azides are readily prepared by an aldol condensation between aryl aldehydes and α-azidoacetates. Provided the necessary aryl aldehyde is available, the indolization of the precursor α-azidocinnamate is practically failsafe. In addition to the indoles in Entries 1 and 2, Kim and colleagues synthesized pyrano[3,2-f]- and pyrano[2,3-g]indoles. The chemistry reported by Rees and coworkers in Entry 5 was employed in a synthesis of the bacterial coenzyme methoxatin. Moody uncovered the novel Claisen-type rearrangement following the Hemetsberger indole synthesis in Entry 6.