C(sp³)‐H Functionalization of 2‐Methyl Azaarenes: Highly Facile Approach to Aza‐Heterocyclic Compounds

Abstract

Quinolines and their derivatives have always been promising leads for drug discovery, material applications and designing new catalysts. In the past decade, C(sp 3 )-H functionalization of 2-methyl azaarenes, particularly 2-methyl quinol- [a] ACYLATIONAlmost the early report of C(sp 3 )-H functionalization of 2methyl quinoline was performed by treating with esters using sodamide or potassium amide as the base. This reaction followed the nucleophilic substitution at the sp 2 center of the ester by the benzylic carbanion which was formed by the base treatment (Scheme 2). A total of 15 compounds were made using this method with the yields ranging from 14-62 %. [11] After a couple of years, another report [12] appeared for this transformation, where 2-methyl quinoline and esters were reacted in the presence of phenyllithium to give corresponding acylated quinolines in 36-80 % yields. Later in 1974, J. F. Wolfe reported another approach by treating 2-methyl quinoline with esters refluxed in dimethoxyethane (DME) using sodium hydride for 1-48 h to obtain the corresponding acylated quinolines in 44-98 % yields. [13] Scheme 2. Minireview

Sequential Organocatalytic Synthesis of [1,2,3]Triazolo[1,5‐a]quinolines

“…Initially, we wondered whether 2-azidobenzaldehyde 1 a and ethyl acetoacetate 2 a could be used as substrates for the synthesis of fused [1,2,3]triazolo[1,5a]quinoline 3 a, through a cascade formation of 1,2,3triazole 4 a and intramolecular condensation reaction, as shown in Scheme 2. The C(sp 3 )À H functionalization of 2-methyl azaarenes is an excellent strategy for the synthesis of new heterocyclic entities, [17] however this type of reaction in methyl 1,2,3-triazoles is rare. [18] With this strategy in mind, and based in the procedure already described by Ramachary and coworkers in 2014, [6c] to prepare 1,2,3-triazoles via enolate using DBU a catalyst, we reacted 2-azidobenzaldehyde 1 a and ethyl acetoacetate 2 a in the presence…”

“…Initially, we wondered whether 2‐azidobenzaldehyde 1 a and ethyl acetoacetate 2 a could be used as substrates for the synthesis of fused [1,2,3]triazolo[1,5‐ a ]quinoline 3 a , through a cascade formation of 1,2,3‐triazole 4 a and intramolecular condensation reaction, as shown in Scheme 2. The C( sp 3 )−H functionalization of 2‐methyl azaarenes is an excellent strategy for the synthesis of new heterocyclic entities, [17] however this type of reaction in methyl 1,2,3‐triazoles is rare [18] …”

Atom‐Economic Alk(en)ylations of Esters, Amides, and Methyl Heteroarenes Utilizing Alcohols Following Dehydrogenative Strategies

“…Hence, it is extremely valuable to develop effective methodologies for the challenging C(sp 3 )−H bond activation leading to the C‐alk(en)ylation of N‐heteroaromatic compounds. Among various methods available in this area, incorporating alkyl moieties using alcohols into the N‐heteroarenes is an important organic transformation [27] . Typically, methylquinolines are selected as model starting materials for the N‐heteroarenes because they are readily available to access alkylated quinoline derivatives.…”

Direct C(sp3)-H allylation of 2-alkylpyridines with Morita-Baylis-Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

“…Therefore, the development of efficient strategies for functionalized pyridine derivatives would be significant in many fields [4][5][6][7]. Although transition mental-catalyzed allylic substitution reactions employing various nucleophilic or electrophilic allylic precursors have been extensively studied [8][9][10], limited strategies were reported for their application in the C(sp 3 )-H allylic functionalization of 2-alkylazaares.…”