Aromatic aza-Claisen rearrangements

Simple aromatic aza-Claisen rearrangement without charge acceleration by addition of an acid required other activating factors to enable the reaction to be run at acceptable temperatures. The reduction of ring strain was found to serve as a useful promoter to induce aromatic aza-Claisen rearrangement [21]. 

An example of an aromatic aza-Claisen rearrangement on water (a term defined due to the lack of water solubility of the reactants) has recently been achieved by McErlean and Beare [57]. They demonstrated the effect by transforming Al-prenylated arylamines (98) into synthetically useful products (99) (Figure 18.7). The developed process was then used to probe the mechanism of the reaction and persuasive evidence in support of the acid-catalysis hypothesis for the on-water effect was obtained. The authors went on to demonstrate the applicability of the reaction with the synthesis of a previously inaccessible heterocyclic naphtho[c]isoxazole scaffold (100) in high yield. 

Water has been shown to catalyse the rearrangement of reverse Af-prenylated naph-thylamines and anilines and reported to make the aromatic aza-Claisen rearrangement synthetically useful (Scheme 31)." ... 

However, the most typical transformation of A-allylanilines is the [3,3]-sigmatropic rearrangement, known as the amino-Claisen rearrangement (46 - 47 48) that has been described in many reviews67-70 (equation 20). This process is sometimes also called the aza-Claisen rearrangement 71 as well as the aromatic aza-Cope rearrangement 72. 

Two reviews written by Majumdar are available that cover the aforementioned chemistry and other advances in the aromatic ort/to-Claisen and aza-Claisen rearrangements [16, 17], What characterizes the Thyagarajan indole syntheses are the very mild conditions (spontaneous) and the excellent yields. 

Gagosz has studied a gold(I)-catalyzed process to convert various allyl pentynyl tosylamides to functionalized pyrroles under mild conditions. Alkyne activation by Au(I) triggers a nuclephilic cyclization of tosylamide to generate the presumed alkenyl gold intermediate 385 which undergoes aza-Claisen rearrangement. Aromatization followed by protodemetalation leads to the pyrrole 387. ... 

The aromatic aza-C.laisen rearrangements of fluorinated A -(l -methylbut-2-enyl(anilines 473 and b have been carried out in refluxing n-xylene in the presence of zinc(II) chloride 39 mixtures of ortho- and /wrn-Claisen products are obtained. In the case of 3,4-difluoro-/V-(1-methylbut-2-enyl)aniline, the product corresponding to 48 predominates, but 4,5-difluoro-yV,2-bis(l -methyl-but-2-enyl)aniline is also formed, which led to the proposal of an intermolecular mechanism. 

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