Synthesis of Polysubstituted Indoles and Indolines by Means of Zirconocene-Stabilized Benzyne ComplexesJeffrey H. Tidwell, Stephen L. Buchwald; J. Am. Chem. Soc.; 1994; 116(26); 11797-11810.
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http://pharmacist.the-hive.tripod.com/polysubstindoles.pdf)
Synthesis of Tryptamine Analogs: We felt that olefins 10 and 11 would be useful not only in the Alder-ene reaction but also as nucleophiles as shown in Scheme 9. We further easoned that iminium salts could act as electrophiles, providing a simple synthesis of tryptamine analogs. Further, since a wide variety of iminium salts can be readily prepared, a wide range of tryptamine analogs would be readily available. Typically, the preparation of dialkyl tryptamine analogs involves multistep syntheses, the yields of which can vary widely, depending upon the substituents on the indole ring. The reaction of olefins 10 and 11 with iminium salts in CH3CN proceeded under extremely mild conditions (45 °C, 2 h) to give 4-iodotryptamine derivatives in excellent yield (Table 2). For example, reaction of 10 with N,N-diethyl-N-methyleneammonium chloride gave diethyltryptamine derivative 26 in 85% yield based on diiodide 8. It is worth noting that the use of 3-methyleneindolines protected as carbamates, such as 25, gives the desired tryptamine products in yields comparable to those protected with alkyl groups (Scheme 10).
