Nitrogen heterocycles are prevalent structures in agrochemicals, pharmaceuticals, and material science. They are also commonly found in natural products and other biologically active molecules. As a consequence, a large number of protocols for the preparation of these nitrogen-containing compounds have become available to synthetic chemists. However, the development of novel methods for the rapid and efficient synthesis of nitrogen heterocycles remains a priority. In particular, methods that are scalable and environmentally friendly are highly valuable, especially if they are reliable across a wide variety of substrates. We recently discovered that iminoquinones, readily accessible by condensation of aliphatic or aromatic primary amines with 1,4-benzoquinones, behave as electrophilic sources of nitrogen. Exploration of this reactivity led to the discovery and development of new methods for the synthesis of pyrroles, indoles and carbazoles. These reactions are characterized by in situ generation of iminoquinone intermediates that undergo acid-catalyzed ring closure with concomitant aromatization of the iminoquinone ring. Condensation of homoallylic primary amines with quinones, followed by a sequence of tautomerization and oxidation events leads to a dienamine intermediate that undergoes acid-catalyzed cyclization to afford N-aryloxy pyrroles. On the other hand, readily accessible 2-vinyl and 2-aryl anilines undergo in situ iminoquinone formation followed by acid-catalyzed cyclization, affording N-aryloxy indoles and carbazoles. These methods require only catalytic ammounts of trifluoroacetic acid and / or triflic acid, and tolerate a wide variety of functional groups, as well as steric and electronic modifications. The discovery, development and evaluation of these transformations will be discussed.

Iminoquinones as a source of electrophilic nitrogen for heterocycle synthesis

2019 Spring National Meeting

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