Aniline derivatives, cascade reaction

Saito and Hanzawa extended their cydoisomerization route, involving the amino-Claisen rearrangement-cyclization cascade reaction (Scheme 9.68), to a one-pot procedure toward the functionalized 2,3-dimethylindole derivatives 281 (Scheme 9.97) [226]. The key propargyl anilines 280 were generated in situ via the propargylation of substituted anilines 278 with the propargrl bromide 279. 

A relay catalytic hydroamination/redox reaction for the synthesis of cyclic aminals 83 from tertiary amine-substituted 3-en-l-yne derivatives 81 and various aniline derivatives 82 was recently developed by Gong and coworkers (Scheme 12.40) [43]. The gold carbene complex [(IPrlAuNTfj] and TfOH were found to be optimal cocatalysts for this cascade reaction. In their preliminary studies, the authors found that this reaction could be carried out in a highly enantioselective manner, despite that 2 equiv. of an expensive chiral phosphoric acid are required. Interestingly, the diastereoselectivity for a particular substrate appears to be independent of the catalyst or ee. This suggests that the enantioselectivity may result from the ring-closure step, rather than the hydride shift step. 

Grigg and Xu have developed a variety of so-called queuing cascades involving allenes. The intra-intermolecular carbopalladation sequence of the <9-iodo-A-methyl-A -(methylallyl)aniline 142 and 1,1-dimethylallene 143 with subsequent / -dehydropalladation leads to the 1,3-dienyl-substituted indole derivative 144, which is immediately trapped by an added dienophile (e.g., A-methylmaleimide) in a Diels-Alder reaction to yield 145 (Scheme 37)7 ... 

Imino-Diels-Alder reaction [49] containing the coupling of imine and electron-rich alkene gradually became a powerful tool for the synthesis of quinazohne derivatives [50], In Povarov imino-Diels-Alder reaction, aniline and ethyl glyoxalate were chosen as substrates. And two molecules of a-iminoesters, which were obtained from the condensation of aniline and ethyl glyoxalate, were hypothesized to form the direct additive product. Cascade imino-Diels-Alder reaction conducted by Chenetal. [51] (Scheme 13.11) was extended from the Povarov imino-Diels-Alder reaction. In this research, researchers chose the same substrates as in the Povarov imino-Diels-Alder reaction, adopted various kinds of Lewis acids as catalysts, and finally produced quinazoline derivatives. Iron powder was determined as the optimized catalyst with highest yields. 

Indole and isoquinolone nuclei are prominent structural units frequently found in numerous natural products and pharmaceutically active compounds. Thus, the search for new methodologies to obtain these scaffolds with different substitution patterns is a current major objective in organic synthesis. Similar to benzofuran synthesis, Aluraez et al. observed that the palladium-catalyzed cascade intramolecular alkyne aminopaUadation/intermolecular Heck-type coupling reaction under oxidative conditions is an efficient methodology for the synthesis of indole 217 and isoquinolone 219 derivatives, starting from readily available aniline 216 or benzamide 218 substrates and functional alkenes [77] (Scheme 6.60). 

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