Oxidative [3+3] Annulation of Atropaldehyde Acetals with 1,3‐Bisnucleophiles: An Efficient Method of Constructing Six‐Membered Aromatic Rings, Including Salicylates and Carbazoles

Abstract

An oxidative [3+3] annulation of atropaldehyde acetals with various 1,3‐bisnucleophiles was developed using either N‐bromosuccinimide or copper(II) bromide as oxidizing reagent and Brønsted or Lewis acids as catalyst. The [3+3] annulations can be considered mechanistically as oxidizing reagent‐induced acid‐acid‐catalyzed domino reactions established through the concept of auto‐tandem catalysis. Alkyl acetoacetates, α‐(indol‐2‐yl)acetate, anilines, 1‐methyl‐1H‐pyrazol‐3‐amine, ethyl 5‐amino‐1H‐pyrazole‐3‐carboxylate, and 3‐amino‐1H‐indazole can all be used as 1,3‐bisnucleophiles in this type of transformation. The established reactions can very efficiently construct six‐membered aromatic rings, including salicylates and carbazoles. A four‐step method of synthesizing the anti‐inflammatory agent diflunisal was also developed based on the oxidative [3+3] annulation reaction, and the yield was high.magnified image

Lewis Acid-Catalyzed Synthesis of Benzofurans and 4,5,6,7-Tetrahydrobenzofurans from Acrolein Dimer and 1,3-Dicarbonyl Compounds

“…Recently, we have found that N -bromosuccinimide (NBS) can act as an oxidizing reagent to cooperate with a Lewis acid catalyst, and the established combined Lewis acid/NBS system can construct five- and six-membered aromatic rings . In this Article, we report a facile way to construct a six-and-five two-aromatic-ring fused heterocycle, namely, benzofuran, by using easily available chemicals, acrolein dimer and 1,3-dicarbonyl compounds, as precursors.…”

Acid‐Acid‐Catalyzed Tandem Reactions Driven by an Additive‐Like Component

“…Our group reported NBS‐assisted Al(OTf) 3 ‐catalyzed [3+3] annulation of atropaldehyde acetals with bisnucleophiles, which can construct aromatic rings with high efficiency (Scheme 4). [19] It was proposed that the reaction proceeded through acascade annulation/aromatization process. Likewise, NBS contributed a significant role in the last aromatization step, and shifted the equilibrium toward the right side.…”

Diversity‐Oriented Metal‐Free Synthesis of Nitrogen‐Containing Heterocycles Using Atropaldehyde Acetals as a Dual C3/C2‐Synthon

“…In the past five years, our group has focused on the reactivity exploration of atropaldehyde acetals and the establishment of cascade process based on atropaldehyde acetals, which acted as multipurpose precursors for various units to construct diverse privileged scaffolds (Scheme 1). [9c,d] For instance, atropaldehyde acetals were utilized as a pivotal C3 fragment to combine with different bisnucleophiles through oxidative [3+3] annulation in the presence of NBS, affording six‐membered aromatic rings, salicylates and carbazoles [9c] . Atropaldehyde acetals were recently demonstrated to be a masked C2 electrophile like a new type of “phenylacetyl or styryl surrogate”, due to the easy cleavage of the carbon‐carbon bond.…”