Domino Aryne Annulation via a Nucleophilic–Ene Process

Abstract

1,2-Benzdiyne equivalents possess the unique property that they can react with two arynophiles through iteratively generated 1,2- and 2,3-aryne intermediates. Upon rational modification on the second leaving group of these aryne precursors, a domino aryne annulation approach was developed through a nucleophilic-ene reaction sequence. Various benzo-fused N-heterocyclic frameworks were achievable under transition metal-free conditions with a broad substrate scope.

Microflow Fluorinations of Benzynes: Efficient Synthesis of Fluoroaromatic Compounds

“…This efficient mixing was particularly beneficial during the microflow reactions of halogenated benzynes 4h-j ( Table 3, Entries 1-3), resulting in the suppression of characteristic side-reactions of halobenzynes, such as the halogen dance reaction, 96) Thia-Fries rearrangement, 93,97,98) and the further formation of other benzynes. [99][100][101][102] The reaction of 3,5-iodobenzyne (4k) seems to be too difficult to be achieved even under microflow conditions probably because of the high leaving ability of the iodo group.…”

Arene Trifunctionalization with Highly Fused Ring Systems through a Domino Aryne Nucleophilic and Diels–Alder Cascade

“…Our previous study revealed that the OTs group on 1 a only departs in a facile manner at about 130 °C, a temperature at which a certain amount of cinnamyl sulfonamide will decompose. Meanwhile, we noticed that an elevated temperature is necessary to propel the intramolecular Diels–Alder reaction with a relatively less active styrene moiety in the 2,3‐aryne ii stage (Table S1), while preventing side reactions.…”

“…Along with our study on aryne chemistry and in line with our goal of preparing biologically active as well as medicinally important molecules using these procedures,– we envisioned that switching the 2,3‐aryne ii reaction partner from an ene–arynophile to one that could incorporate two substituents other than hydrogen would enable aryne trifunctionalization. 1,3‐Dienes were thus chosen, and 1,2,3‐trisubstituted arenes with [6, n ,6]‐tricyclic system could be conceived through a cascade nucleophilic and [4+2] cycloaddition process with our domino aryne precursors (Scheme b).…”

“…Furthermore, a breakthrough was realized by combining two different types of arynophiles in the same cascade process. To this end, a domino aryne nucleophilic‐ene reaction was successfully accomplished (strategy II, Scheme a) . Despite the fact that this method is amenable to the preparation of natural related indoline scaffolds, its drawback resides in only 1,2‐difunctionalization with the formation of a C−H bond at the C3‐position of the benzene ring.…”

Discussion Addendum for: The Direct Acyl-Alkylation of Arynes. Preparation of Methyl 2-(2-acetylphenyl)acetate

“…60 The Li group discovered that these latent 1,2benzdiynes can also participate in ene reactions. 61…”