Abnormal Nucleophilic Substitution on Methoxytropone Derivatives: Steric Strategy to Synthesize 5‐Substituted Azulenes

Abstract

Azulene is an on-alternant non-benzenoid aromatic system,a nd in turn, it possesses unusualp hotophysical properties. Azulene-based conjugated systems have received increasing interesti nr ecent years as optoelectronic materials. Despite the routes available for the preparationo fs ubstituted azulene derivatives, there remain few methods that allow regioselective substitution on the seven-membered ring of azulenes due to the subtle reactivity difference among the various positions. This report explores the reactivity of substituted tropolones as the azulene precursors and also provides anew method to create 5-substitutedazu-lenes. The reactiono fc yanoacetate enolate with unsubstituted 2-methoxytropone affords azulene through the attack of the nucleophile on the C-2 center( normal pathway). We have observed that 3-substituted 2-methoxytropones undergo steric-guided nucleophilic addition at the C-7 center (abnormalp athway) to afford 5-substituteda zulene derivatives. Based on this observation and DFT calculation, an ew synthetic strategy is devised for the regioselective synthesis of 5-substituted multifunctional azulenes, which cannot be accessed by any other method.Scheme1.Various approaches to azulene synthesis.[a] N.Supporting information (containingd etailed experimental procedures for the synthesis of all precursors and the azulene derivatives and references for compounds reported elsewhere) and the ORCID identification number(s) for the author(s)oft his article can be found under: https://doi.

The Effect of Base and Nucleophile on the Nucleophilic Substitution of Methoxytropone Derivatives: An Easy Access to 4- and 5-Substituted Multifunctional Azulenes

“…The strength of the amine bases follows the following trend: DBU > DIPA > t -BuNH 2 > Bu 3 N > Et 3 N > DIPEA > DABCO. We attempted azulene synthesis reaction with model substrate 1b using each of MLN/MCA/ECA with the bases NaOMe/DBU/DIPA/ t -BuNH 2 /Bu 3 N/Et 3 N/DIPEA/DABCO following the general reaction conditions as reported earlier. , …”

“…Methyl ethers of propyl-, allyl-, phenyl-, naphthyl-, and 3-thienyl-substituted tropolones ( 1b / 1c , 9b / 9c , 10b / 10c , 11b / 11c , and 12b / 12c , respectively) were synthesized using the procedures reported in the literature. ,, 1 H NMR data of all the tropolone derivatives matched with those reported earlier.…”

“…In our previous work, we developed a simple steric-based strategy for the regioselective synthesis of 5-substituted multifunctional azulenes from 3-substituted 2-methoxytropones, which undergo an abnormal nucleophilic attack by the cyanoacetateenolate at C-7 to form 5-substituted azulene rather than the expected normal attack at C-2 to form 4-substituted azulene (Scheme 1B). 16 In this work, we explore the influence of nucleophiles and bases of varying steric bulk and strength on the nucleophilic substitution on 3-and 7-substituted 2methoxytropones (Scheme 1C). This study has paved paths for the efficient regioselective synthesis of both 4-and 5substituted multifunctional azulenes.…”

“…Synthesis of functionalized/substituted azulenes has been difficult due to the lack of appropriate methods for the generation of azulenes from prefunctionalized precursors, and the common strategy toward substituted azulenes has been the postfunctionalization of the azulene skeleton. In our previous work, we developed a simple steric-based strategy for the regioselective synthesis of 5-substituted multifunctional azulenes from 3-substituted 2-methoxytropones, which undergo an abnormal nucleophilic attack by the cyanoacetate-enolate at C-7 to form 5-substituted azulene rather than the expected normal attack at C-2 to form 4-substituted azulene (Scheme B) . In this work, we explore the influence of nucleophiles and bases of varying steric bulk and strength on the nucleophilic substitution on 3- and 7-substituted 2-methoxytropones (Scheme C).…”

Recent Advances in the Functionalization of Azulene Through Pd‐Catalyzed Cross‐Coupling Reactions

“…Zade et al . recently discovered that 3‐substituted 2‐methoxytropones undergo steric‐guided nucleophilic addition at the C‐7 center (abnormal pathway) to yield 5‐substituted azulene derivatives [56] …”