A Straightforward Approach to Fluorinated Pyrimido[1,2-b]indazole Derivatives via Metal/Additive-Free Annulation with Enaminones, 3-Aminoindazoles, and Selectfluor

Abstract

A novel and efficient three-component reaction with two C−N bonds and one C−F bond formation has been reported, which provides a straightforward route to a variety of fluorinated pyrimido[1,2-b]indazole derivatives. This transformation has the advantage of excellent functional group compatibility, including aliphatic and aromatic substituents enaminones. Moreover, metal and additives are not necessary for this reaction, which is of great significance for the synthesis and application of fluorinated heterocycles.

Cu-catalyzed oxidative denitrogenation of 3-aminoindazoles for the synthesis of isoquinolinones

“…According to the experimental results and reported literature, 5,6,9 we proposed a probable mechanism (Scheme 4). Firstly, 3-aminoindazole 1a was oxidized to intermediate A .…”

“…5 f In addition, 3-aminoindazoles could be used for constructing fused heterocycles through condensation with carbonyl compounds. 6 For instance, Bai's group reported a NH 4 I-mediated difunctionalization of triethylamine for the construction of fused nitrogen-containing heterocycles in 2019 (path IV, Scheme 1). 6 a In 2021, He and Cao's group disclosed a Ag-catalyzed effective method to construct pyrimido[1,2- b ]indazole derivatives from 3-aminoindazoles and ynals (path V, Scheme 1).…”

“…Cu( ii ) species and TBHP underwent a single electron transfer (SET) process, delivering the tert -butoxyl radical and Cu( iii ) species. 5,6 Next, the tert -butoxy radical grabs the hydrogen atom of intermediate A , followed by N 2 evolution, to give the cyano-substituted aryl radical B . Subsequently, radical B reacted with 1a via a radical addition process.…”

Recent advances in 3-aminoindazoles as versatile synthons for the synthesis of nitrogen heterocycles

“…With the continuing efforts on the development of new synthetic methods to access various functionalized pyrimido[1,2- b ]indazoles, the same group treated 3-amindazoles and enaminones with Selectfluor in ethylene glycol and H 2 O; the fluorinated pyrimido[1,2- b ]indazoles were afforded via the formation of two C–N bonds and one C–F bond. 30 Satisfactorily, the reaction scope was quite broad and a wide range of structurally diverse fluorinated products were obtained in acceptable yields under the optimized conditions. According to the probable mechanism (Scheme 21), the initial step was an electrophilic fluorination rather than a nucleophilic addition.…”

Visible-light-promoted radical cascade alkylation/cyclization: access to alkylated indolo/benzoimidazo[2,1-a]isoquinolin-6(5H)-ones

“…In recent years, significant progress in the preparation of indolo/benzoimidazo-fused nitrogen-containing polycyclic compounds has been achieved via intermolecular cycloaddition. 2–4 For example, in 2018, Song and co-workers reported a rhodium( iii )-catalyzed [4 + 2] annulation reaction between 2-arylimidazoles and α-diazoketoesters for the preparation of benzimidazole[2,1- a ]isoquinoline derivatives (Scheme 1a). 2 d This method involves an efficient strategy, which involves the pre-functionalization of the imidazole N–H bond and greatly simplifies the synthetic route for the preparation of substituted indolo/benzoimidazo[2,1- a ]isoquinolin-6(5 H )-ones.…”