Kita indole synthesis

Some 40 years earlier, Harley-Mason and Cromartie synthesized 5-hydroxyindole in excellent yield via the oxidation of 2,5-dihydroxyphenylalanme with potassium ferricyanide (Scheme 6, equation 1) [9]. This simple oxidation when applied to 2,3-dihydroxypheny-lalanine gave 7-hydroxyindole in 20% yield [9] and 3,4-dihydroxyphenylalanine gave 5,6-dihydroxyindole in 30% yield (but not repeatable) [10], This simple oxidation procedure with ferricyanide was used to synthesize bufotenine and serotonin [11], In chemistry related to the Kita indole synthesis, Clive and Stoffman presented a synthesis of 4-halo-5-hydroxyindoles from the corresponding coumarins... 

The Engler-Kita indole synthesis, combined with the Nenitzescu indohzation, represent powerful and versatile syntheses of 5-hydroxyindoles. 

Scheme 6 Applications of the Engler-Kita Indole Synthesis...

While the Engler indole synthesis has not been pursued by others, Kita and coworkers developed a related intramolecular amine cyclization onto benzoquinones leading to 5-oxygenated indoles (Scheme 4) [7]. The yields are excellent, and several examples are shown (yields are overall from the starting quinones or quinone acetal). 

A general and efficient synthesis of 5-oxygenated indoles 126 and 128 has been reported by Kita et al. (92H503). The method involves intramolecular imine formation from p-benzoquinones 125 and p-benzoquinone monoacetals 127 bearing the 2-aminoethyl side chain. Compounds 125 and 127 are prepared by the oxidation of 124 with IBTA in acetonitrile in the presence of water and methanol, respectively (Scheme 35). 

Kita has described an excellent synthesis of 5-oxygenated indoles viathephenyliodine (III) bis(trifluoroacetate) (PIFA) oxidation of 2-aminoethyl oxygenated phenols (Scheme 2, equations 1 and 2) [5]. This method was extended to the preparation of 5-hydroxyindole, 5-methoxyindole, and 7-bromo-5-hydroxyindole in 65% to 100% yield from the requisite quinone or quinone acetal. 

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