Synthesis of 1‐Heteroaryl‐ and 1,3‐Bis(heteroaryl)azulenes: Electrophilic Heteroarylation of Azulenes with the Triflates of N‐Containing Heteroarenes

Abstract

An efficient synthesis of 1‐heteroaryl‐ and 1,3‐bis(heteroaryl)azulenes was established by electrophilic substitution. The reaction of azulenes and 1,1′‐biazulene with the triflate of N‐containing heteroarenes proceeded smoothly in the presence of excess heteroarenes to afford the corresponding 1‐dihydroheteroaryl‐ and 1,3‐bis(dihydroheteroaryl)azulene derivatives in good yields. The 1‐dihydroheteroaryl‐ and 1,3‐bis(dihydroheteroaryl)azulene derivatives were readily converted into the desired 1‐heteroaryl‐ and 1,3‐bis(heteroaryl)azulenes by treatment with tBuOK in DMSO or KOH in EtOH in excellent yields. The pyridinium salts 26+·I– and 272+·2I– were also prepared by the reaction of 4a and 5a with methyl iodide. 1‐Heteroaryl‐ and 1,3‐bis(heteroaryl)azulenes exhibited a significant color change in acetic acid from that in dichloromethane due to the development of intramolecular charge‐transfer (CT) absorption bands.

Azulene Functionalization by Iron-Mediated Addition to a Cyclohexadiene Scaffold

“…Synthesized according to general procedure B using azulene derivative 8 (20.6 mg, 0.101 mmol), iron complex 6 (40.5 mg, 0.111 mmol), and NaHCO 3 (16.9 mg, 0.202 mmol). The product was purified by flash chromatography (100% petroleum ether), yielding 13 as a blue-green solid (40.6 mg, 95%); mp 51−55 °C; 1 H NMR (400 MHz, chloroform-d) δ 8.41 (dd, J = 9.7, 0.9 Hz, 1H), 8.23 (d, J = 9.5 Hz, 1H), 7.84 (s, 1H), 7.61−7.56 (m, 2H), 7.55−7.46 (m, 3H), 7.35 (app ddt, J = 7.9, 6.8, 1.3 Hz, 1H), 7.06 (app t, J = 9.8 Hz, 1H), 7.03 (app t, J = 9.7 Hz, 1H), 5.59 (ddd, J = 6.5, 3.3, 2.0 Hz, 1H), 5.46 (ddd, J = 5.9, 4.1, 1.5 Hz, 1H), 4.06 (dt, J = 11.2, 3.6 Hz, 1H), 3.33 (ddd, J = 6.4, 3.6, 1.4 Hz, 1H), 3.31−3.27 (m, 1H), 2.57 (ddd, J = 15.2, 11.1, 3.8 Hz, 1H), 1.90−1.83 (m, 1H); 13 Tricarbonyl[1-(4-methoxycyclohexa-2,4-dien-1-yl)-3phenylazulene]iron (14). Synthesized according to general procedure B using azulene derivative 8 (100 mg, 0.490 mmol), iron complex 7 (212 mg, 0.539 mmol), and NaHCO 3 (82.3 mg, 0.979 mmol) in 4.0 mL acetone.…”

“…Azulenes are potent nucleophiles for electrophilic aromatic substitution (S E Ar), with the 1- and 3-positions being the most reactive toward electrophiles . Reported methods for derivatizing azulenes include (a) the Michael addition, (b) Friedel–Crafts , and Vilsmeier–Haack reactions, , (c) azulene addition to heteroaromatic triflates, and (d) the formation of diazo compounds (Scheme ). Azulenes are also susceptible to (e) electrophilic halogenations. , In addition, cross-coupling reactions have been reported .…”