Functionalization Of Methyl Azaarenes Research Articles

Catalyst-free C(sp3)-H functionalization of methyl azaarenes with heteroaromatic trifluoromethyl ketone hydrates: "all-water" synthesis of α-trifluoromethyl tertiary alcohols.

An efficient catalyst-free C(sp3)-H bond functionalization of methyl azaarenes with heteroaromatic trifluoromethyl ketone hydrates in neat water has been developed for the synthesis of α-trifluoromethyl tertiary alcohols bearing N-heteroaromatics. This method not only features excellent efficiency, broad substrate scope, catalyst-free conditions, and easy gram-scale preparation but also represents a new and rare example of "all-water" synthesis of trifluoromethylated molecules.

Recent Opportunities and Challenges in Selective C-H Functionalization of Methyl Azaarenes: A Highlight from 2010 to 2020 Studies.

Azaarenes are unique scaffolds that are frequently found in pharmaceuticals. Herein we have summarized the recent synthetic available methods in C-H functionalization of methylazaarenes from 2010 to 2020. Multiple approaches involving halogenation, alkylation via different methods, alkenylation, oxidative functionalization, and cyclization of the methylazaarenes will be discussed in this review.

Iron-catalyzed benzylic addition of 2-methyl azaarenes to substituted trifluoromethyl ketones

This paper demonstrated a new and economical methodology using Fe(ClO4)2·H2O as a catalyst for the direct C(sp3)–H functionalization of 2-methyl azaarenes via addition to trifluoromethyl ketones. The use of Fe salts as a Lewis acid catalyst has shown great potential as an accessible, affordable, and effective catalyst for the reaction. Under mild, optimized conditions, an extensive range of 2-alkenylated azaarenes was produced with yields of up to 95%.

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

Quinolines and their derivatives have always been promising leads for drug discovery, material applications and designing new catalysts. In the past decade, C(sp3)‐H functionalization of 2‐methyl azaarenes, particularly 2‐methyl quinolines, has become one of the highly facile synthetic routes for the generation of new chemical libraries of quinolines. In this minireview, we showcase the synthetic endeavors on C(sp3)‐H functionalization of 2‐methyl quinolines.

Direct C(sp3)-H functionalization of 2-methylazaarenes using 4-substituted-TEMPO

An efficient and direct C(sp3)-H functionalization of 2-methyl azaarenes with persistent nitroxide radical 4-substituted-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) under neutral conditions has been developed. A broad of 2-methylazaarenes could be reacted with 4-substituted TEMPOs to afford corresponding azaarene 2-methoxylamines by using cheaper copper (II) acetate hydrate as oxidant.

Correction to “Highly Regioselective Synthesis of Oxindolyl-Pyrroles and Quinolines via a One-Pot, Sequential Meyer–Schuster Rearrangement, Anti-Michael Addition/C(sp3)–H Functionalization, and Azacyclization”

[This corrects the article DOI: 10.1021/acsomega.8b00147.].

Highly Regioselective Synthesis of Oxindolyl-Pyrroles and Quinolines via a One-Pot, Sequential Meyer-Schuster Rearrangement, Anti-Michael Addition/C(sp3)-H Functionalization, and Azacyclization.

A one-pot, sequential Meyer–Schuster (MS) rearrangement of oxindole-derived propargyl alcohols to the corresponding α,β-unsaturated enones and their anti-Michael addition, followed by intramolecular azacyclization is described in a highly regioselective manner using Ca(OTf)2 as the promoter. Further, we described the one-pot MS rearrangement, followed by C(sp3)–H functionalization of 2-methyl azaarenes at α-carbon of these doubly activated alkenes. Control experiments and computational calculations were performed to propose the reaction mechanism.

ChemInform Abstract: Alkaline‐Earth‐Catalyzed sp3 C—H Functionalization of Methyl Azaarenes and Its Use in a One‐Pot Four‐Component Synthesis of Azaarenyl Benzylpyrazolones.

AbstractFor the first time, calcium triflate is used to catalyze a 4‐component reaction between aldehydes, 2‐methylquinolines, ethyl acetoacetate, and arylhydrazines to give 1‐aryl‐3‐methyl‐4‐ [2‐(quinolin‐2‐yl)‐1‐aryl/alkyl‐ethyl]‐2H‐pyrazol‐5‐ones.

ChemInform Abstract: ′On Water Synthesis′ of Oxindoles Bearing Quaternary Carbon Center Through C—H (sp3) Functionalization of Methyl Azaarenes.

A catalyst-free and green approach of sp3 C–H functionalization of methyl azaarenes with malononitrile and isatins for the synthesis of oxindole derivatives bearing quaternary carbon center has been described in water. This one-pot three component synthesis endures the key features like first ‘on water synthesis’, short reaction times, moderate to good yields, and large substrate scope.

ChemInform Abstract: C(sp3)—H Functionalization of Methyl Azaarenes: A Calcium‐Catalyzed Facile Synthesis of (E)‐2‐Styryl Azaarenes and 2‐Aryl‐1,3‐bisazaarenes.

AbstractA mild, efficient, and sustainable catalytic system for the C(sp3)—H functionalization of methyl azaarenes is reported.

‘On water synthesis’ of oxindoles bearing quaternary carbon center through C–H (sp3) functionalization of methyl azaarenes

A catalyst-free and green approach of sp3 C–H functionalization of methyl azaarenes with malononitrile and isatins for the synthesis of oxindole derivatives bearing quaternary carbon center has been described in water. This one-pot three component synthesis endures the key features like first ‘on water synthesis’, short reaction times, moderate to good yields, and large substrate scope.

Alkaline-Earth-Catalyzed sp3 C–H Functionalization of Methyl Azaarenes and Its Use in a One-Pot Four-Component Synthesis of Azaarenyl Benzylpyrazolones

The sp³ C–H functionalization of methyl azaarenes by using calcium triflate as the catalyst is described, together with its use in the first synthesis of azaarenyl benzylpyrazolones by a one-pot four-component reaction.

ChemInform Abstract: Iron‐Catalyzed C(sp3)—H Functionalization of Methyl Azaarenes: A Green Approach to Azaarene‐Substituted α‐ or β‐Hydroxy Carboxylic Derivatives and 2‐Alkenylazaarenes.

AbstractBioactive azaarene‐substituted lactic acids, β‐hydroxy esters, hydroxyindolones, and alkenylazaarenes are prepared via C(sp3)—H functionalization of methyl azaarenes with carbonyl compounds in the presence of iron(II) acetate as an inexpensive, nontoxic, and efficient catalyst.

β-Cyclodextrin catalysed C–C bond formation via C(sp3)–H functionalization of 2-methyl azaarenes with diones in aqueous medium

β-Cyclodextrin catalysed C(sp3)–H functionalization of 2-alkyl-azaarenes with homocyclic as well as heterocyclic diones in water has been developed. This biomimetic catalyst oriented methodology provides a sustainable protocol for C–H functionalization, an area mainly dominated by transition metals.

ChemInform Abstract: Iron‐Catalyzed C(sp3)—H Functionalization of Methyl Azaarenes with α‐Oxoesters: A Facile Approach to Lactic Acid Derivatives.

AbstractFe(OAc)2 was used as catalyst for the reaction of ethyl glyoxylate or pyruvates with 2‐methylquinolines, 2‐methylpyridines, 2‐methylquinoxaline and 1‐methylisoquinoline to achieve the corresponding azaarene‐derived lactic acid derivatives.

Triflic acid-catalyzed [formula omitted] functionalization of 2-methyl azaarenes with a α-trifluoromethyl imino ester

A Brønsted acid promoted Csp3–H functionalization of 2-alkyl azaarenes with α-trifluoromethylated imino ester is described. A catalytic amount of triflic acid provided straightforward access to the corresponding trifluoromethylated amino esters via concomitant in situ one step N-alkyl deprotection. On further hydrolysis of ester, synthesis of quinoline derived unnatural trifluoromethylated amino acids has been achieved in a short and efficient manner.

Iron-catalyzed C(sp3)–H functionalization of methyl azaarenes: a green approach to azaarene-substituted α- or β-hydroxy carboxylic derivatives and 2-alkenylazaarenes

An iron-catalyzed C(sp3)–H functionalization of methyl azaarenes with carbonyls to access the title compounds have been described.

ChemInform Abstract: Lewis Acid Catalyzed Csp3—H Functionalization of Methyl Azaarenes with α‐Trifluoromethyl Carbonyl Compounds.

AbstractYtterbium triflate is found to be highly efficient for the title reaction, delivering trifluormethylated alcohols in excellent yields.

A novel and efficient synthesis of azaarene-substituted 3-hydroxy-2-oxindoles via sp3 C–H functionalization of 2-methyl azaarenes and (2-azaaryl)methanes over a heterogeneous, reusable silica-supported dodecatungstophosphoric acid catalyst

A novel and efficient protocol has been developed for the synthesis of azaarene-substituted 3-hydroxy-2-oxindoles via sp3 C–H functionalization of 2-methyl azaarenes and (2-azaaryl)methanes with isatin in good to excellent yield. This is the first example in which heterogeneous, reusable silica supported dodecatungstophosphoric acid (DTP/SiO2) catalyzed sp3 C–H functionalization of 2-substituted azaarenes and (2-azaaryl)methanes.

Brønsted acid promoted benzylic C–H bond functionalization of azaarenes: nucleophilic addition to aldehydes

A practical Brønsted acid promoted benzylic C-H functionalization of 2-methylazaarenes and nucleophilic addition to aldehydes was developed in good to excellent yields. A six-membered hydrogen-bonding transition state is proposed to be crucial for the reaction. Ready availability of the two starting materials, the use of acetic acid as the catalyst and the facile reaction conditions will guarantee this synthetic method attractive to the synthesis of bioactive pyridine and quinoline derivatives.