Hydroxyindoles, synthesis

NENITZESCU 5-Hydroxyindole Synthesis 5-Hydroxyindole synthesis from quinones and p-aminocrotonates (see 1st edition). 

Although Nenitzescu is best known for his 5-hydroxyindole synthesis (Chapter 15), he and his colleagues pioneered the reduction and cyclization of ort/jo-p-dinitrostyrenes to indoles. This classic reaction paved the way for other indole ring syntheses involving the reduction of nitroarenes. Nenitzescu described the inaugural reaction in 1925 as shown in Scheme 1, equation 1 [1], The o,p-dinitrostyrene was prepared by the base-catalyzed condensation of... 

The Nenitzescu indole synthesis involves the condensation of a quinone 1 and an enamine 2 to generate a hydroxyindole 3. 

The choice of experimental conditions exerts a major influence on the course of Nenitzescu procedure and thereby determines the structure of the major product. The mechanism demonstrated to be operative for the method can be employed to understand the genesis of certain anomalous products and suggests ways to avoid them, thus increasing the efficiency of the synthesis of 5-hydroxyindoles. 

Since the last review (76AHCS1, p. 240), progress has been made in the synthesis of A-hydroxyindoles (83JOC3639 94C4991 97T5501). Com-... 

Its structural determination had to wait for 25 years until 1998 (98H2481), when we reached the stage where we could apply suitable characteristic reactions found in 1-hydroxyindole chemistry to the synthesis of the authentic 6-ethoxy-2-phenylindole (148). 

The first total synthesis of 87 was published in 1990 (90TL1523). 5-Hydroxyindole (88) was mesylated and then reduced with sodium cyanoborohydride to give an indoline which was brominated to afford the bromoindoline 89 in good yield (Scheme 33). Cross-coupling with ortho-formyl boronic acid under Suzuki conditions, followed by air oxidation of the resulting cyclized product, followed by reduction of the lactam formed with excess Red-Al gave the target compound 87. 

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