Conjugate Additions to Vinyl-Substituted Aromatic N-Heterocycles

Abstract

Conjugate or Michael addition to vinyl-substituted aromatic N-heterocycles has been a useful synthetic method for the synthesis of functionalized heterocyclic compounds. A wide variety of heterocycles and nucleophiles undergo this chemistry. Recent work in this area has utilized transition-metal catalysts and some asymmetric synthesis has been accomplished. An overview of this chemistry is presented in this account.

Enantioselective Aza Michael‐Type Addition to Alkenyl Benzimidazoles Catalyzed by a Chiral Phosphoric Acid

“…An ideal example of this type of construction is the conjugate addition to an alkenyl moiety, having an electron‐deficient aromatic N‐heterocycle (azaarene), a reaction which is an analogue of the classical Michael addition to an α,β‐unsaturated carbonyl compound. This particular transformation is often seen in biosynthesis, and has also been developed by synthetic chemists into a beneficial synthetic method . However, asymmetric conjugate addition to alkenyl azaarenes has been less exploited and remains a challenging task .…”

“…To validate the transformation envisaged, we employed benzimidazole as the aromatic N‐heterocyclic unit for the alkenyl azaarene. While many five‐ or six‐membered aromatic N‐heterocycles (e.g., thiazole, pyridine, and pyrimidine) have been reported as basal units of the alkenyl azaarenes for Michael‐type additions, the alkenyl benzimidazoles 2 (Figure b) have never been used in the proposed MTA, despite benzimidazoles being typical elements of biologically active compounds . The reactivity of 2 as well as the stereochemical outcome of the addition products could be tuned through the choice in the protecting group at the nitrogen atom of the benzimidazole moiety.…”

Photoredox-catalyzed branch-selective pyridylation of alkenes for the expedient synthesis of Triprolidine

“…yridine is recognized as one of the most important heterocycles in pharmaceuticals, agrochemicals, and bioactive natural products 1,2 . Alkenylpyridines, an important subunit of pyridines, also serve as versatile synthetic building blocks for complex pyridines 3,4 , as well as important ligand scaffolds in the area of catalysis (Fig. 1a) 5 .…”

Bifunctional iminophosphorane catalysed enantioselective sulfa-Michael addition of alkyl thiols to alkenyl benzimidazoles

“…Their functionalization, especially when performed in an enantioselective manner, is therefore of particular interest in the field of organic synthesis. Alkenyl azaarenes have been used extensively as synthetic precursors for the functionalization of N-containing heterocycles 1. The electron deficiency of the aromatic ring, part-activates the conjugated alkene towards Michael-type additions,2 allowing for the rapid generation of molecular complexity.…”