3//-Indoles, 3-halo-, formation

Reaction sequences involving halogen transfer, followed by non-radical interception of the alkyl iodide or bromide formed can allow for the trapping of products arising from less exothermic or even endothermic atom transfer additions and are exemplified in Scheme 11. Yoon [30] and Curran [31] have demonstrated that the a-halo ethers formed upon addition to vinyl ethers can be trapped with alcohols, leading to formation of acetals. Substitution reactions on the heteroaromatics pyrrole and indole have been carried out through a sequence of steps involving I- or Br-... 

This reaction was first reported by Hantzsch in 1890. It is the preparation of 2,5-dialkyl or 2,4,5-trialkylpyrrole derivatives from the condensation of of-halo-ketones, )0-ketoesters and ammonia or amines. Therefore, it is often known as the Hantzsch pyrrole synthesis or simply the Hantzsch synthesis. During this synthesis, ammonia or amine reacts quickly with y0-keto esters to form enamine esters or 3-amino crotonates that cyclize with of-halo-ketones to form pyrrole derivatives upon heating, and the regioselectivity strongly depends on the substituents on the starting materials. Thus, this reaction can directly start from 3-amino crotonates or enamines of 0-keto esters. Further extension of this reaction from aromatic amines results in the formation of indole derivatives, or carbazole derivatives if cyclized with a-halo-cyclohexanones. The synthesized pyrroles have wide application in medicinal chemistry, conducting polymers, molecular optics, sensors,etc. 

Wu and coworkers in 2014 explored a [3 4-2] cycloaddition between substituted indoles and oxyallyl dipoles, derived in situ from dehalogenation via enolization of a-halo ketones. Applying their method toward the synthesis of the echitamine core, they first treated a solution of protected trypt-amine 200 and a-chlorocyclopentanone (199) in trifluoroethanol with sodium carbonate (Scheme 21). These conditions eHcited formation of the... 

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