3-Trifluoromethylbenzyne: Precise Orientation in Cycloaddition Reaction Enabled Regioselective Synthesis of Trifluoromethylated Triptycenes

Abstract

The first regioselective addition reactions to 3-trifluoromethylbenzyne are reported. Triple cycloaddition of ynolates to the benzyne provided 1,8,13-tris(trifluoromethyl)triptycenes with high regioselectivity. 1-Trifluolomethyltriptycene was regioselectively obtained by the Diels-Alder reaction of anthranoxide with benzyne. These selectivities are attributed to the electron acceptor nature of the trifluoromethyl group on the benzyne.

Trifluoromethoxylation of Arynes Using 2,4‐Dinitro‐1‐(trifluoromethoxybenzene) as Trifluoromethoxide Anion Source

“…Finally, the trifluoromethoxylation conditions applied to the 3‐piperidyne precursor 2 m gave a low isolated yield of 12 % of 3 m as a single regioisomer. In terms of regioselectivity preferences, the results obtained for 3 e – f , h , j – m are in accordance with calculations reported by Santelli et al ., [20] Garg, Houk et al ., [21] and Iwata, Shindo et al [22] . regarding the distortion angle of the active triple bond.…”

Arynes as synthetic linchpins towards the construction of diversely functionalized natural product skeletons

“…products. [11][12][13][14][15] Among them, the synthetic organic chemists have been enticed to aryne intermediates due to their highly reactive nature, [16][17][18][19][20][21][22] and are well known for their diverse synthetic scaffolding to carbocycles, 23 heterocycles, 24 natural products 22,25 and pharmaceutically pertinent drug molecules. 26 Arynes 1 are a unique class of highly reactive and transient intermediates with a strained triple bond that enables them to be versatile electrophilic building blocks in their reactions with nucleophiles to afford functionalized adducts.…”

“…6–10 Several synthetic intermediates have been reported to synthesize bioactive natural products. 11–15 Among them, the synthetic organic chemists have been enticed to aryne intermediates due to their highly reactive nature, 16–22 and are well known for their diverse synthetic scaffolding to carbocycles, 23 heterocycles, 24 natural products 22,25 and pharmaceutically pertinent drug molecules. 26…”