Aerobic α,β-C(sp³)–H Bond Difunctionalization and C–N Bond Cleavage of Triethylamine: Difunctional Ammonium Iodide Enabling the Regioselective Synthesis of 4-Arylpyrimido[1,2-b]indazoles

Abstract

A novel method for the regioselective synthesis of 4-aryl­pyrimido­[1,2-b]­indazoles has been developed via the dual C­(sp3)–H bond functionalization and C–N bond cleavage of triethylamine. The elusive acyclic enamine intermediates are effectively in situ generated and captured by aromatic aldehydes to form a wide array of tricyclic products from 3-aminoindazoles under the NH4I-mediated aerobic oxidative conditions. This reaction features easily available feedstock, green and economic conditions, and valuable products.

Controllable Site-Selective Construction of 2- and 4-Substituted Pyrimido[1,2-b]indazole from 3-Aminoindazoles and Ynals

“…On the basis of the experimental results and the literature reports, , the possible reaction mechanisms were proposed in Scheme . First, for the formation of 3a , the condensation of 1a and 2a yielded the intermediate I , which underwent the 6- endo-dig cyclization activated by a Ag catalyst to form the final product.…”

“…Unfortunately, few efforts have been devoted to the development of efficient access to these compounds. Recently, the condensation of 3-aminoindazoles with carbonyl compounds was demonstrated to be an effective approach to synthesize pyrimido­[1,2- b ]­indazoles derivatives. , For example, Song’s group developed a Lewis acid promoted condensation of 3-aminoindazoles with 3-ethoxycyclobutanones and Gao’s group discovered a NH 4 I-mediated three-component reaction of 3-aminoindazoles, aromatic aldehydes, and ethyl amines . However, these tactics only produce 4-substituted pyrimido­[1,2- b ]­indazoles.…”

Synthetic Route to Enaminones via Metal-Free Four-Component Sequential Reactions of Aryl Olefins with CHCl3, Et3N, and TBHP

“…Based on the above results and related work, ,, we proposed a tentative mechanism for the formation of enaminone 7a (Scheme ). First, • CHCl 2 and t BuOO • radicals are generated by the reaction with TBHP, which then add to the styrene sequentially, forming the intermediate product 5a .…”

Synthesis of Substituted Pyrimido[1,2‐b]indazoles through (3+2+1) Cyclization of 3‐Aminoindazoles, Ketones, and N,N‐Dimethylaminoethanol as One‐Carbon Synthon

“…demonstrated a chemoselective condensation of 3‐aminoindazoles with 3‐ethoxycyclobutanones promoted by a Lewis acid (Scheme 1a) [10] . Gao reported an NH 4 I‐promoted multi‐component oxidation of 3‐aminoindazoles, aromatic aldehydes and triethylamine (Scheme 1b) [11] . However, these strategies only gave 4‐substituted pyrimido[1,2‐ b ]indazoles.…”

“…[10] Gao reported an NH 4 I-promoted multi-component oxidation of 3aminoindazoles, aromatic aldehydes and triethylamine (Scheme 1b). [11] However, these strategies only gave 4substituted pyrimido [1,2-b]indazoles. Very recently, Cao et al demonstrated their fantastic finding that 2and 4-substituted pyrimido [1,2-b]indazoles could be selectively constructed from 3-aminoindazoles and ynals by using different catalytic systems (Scheme 1c).…”