Synthesis of Difluoroarymethyl-Substituted Benzimidazo[2,1-a]isoquinolin-6(5H)-ones under Mild Conditions

Abstract

A highly efficient method for synthesis of difluoroarymethyl-substituted benzimidazo[2,1-a]isoquinolin-6(5H)-ones using 2-arylbenzoimidazoles with α,α-difluorophenylacetic acid as reaction substrates has been developed through radical cascade cyclization. The advantage of this strategy lies in excellent functional group tolerance to generate the corresponding products in good yields under base- and metal-free conditions.

Use of caps in the auxiliary basis set formulation of the fragment molecular orbital method

“…In the applications of FMO to biochemical 92–95 and inorganic 96,97 systems, it is desirable to improve the quality of theoretical predictions by using larger basis sets. Fragment properties can be used as descriptors in machine learning models 98 .…”

Electrochemical Radical Tandem Difluoroethylation/Cyclization of Unsaturated Amides to Access MeCF2-Featured Indolo/Benzoimidazo [2,1-a]Isoquinolin-6(5H)-ones

“…5-(2,2-Difluoropropyl)-5-methylbenzo [4,5]imidazo [2,1-a]isoquinolin-6(5H)-one (3a) [39]. A white solid after purification by flash column chromatography (petroleum ether/ethyl acetate = 10/1), mp 153-154 5-(2,2-Difluoropropyl)-3,5-dimethylbenzo [4,5]imidazo [2,1-a]isoquinolin-6(5H)-one (3b).…”

“…Benzo [4,5]imidazo[2,1-a]isoquinolines and indolo [2,1-a]isoquinolines, which are significant classes of fused polycyclic nitrogen-containing scaffolds, widely exist in natural products and pharmaceuticals (Figure 1(1)) [27][28][29][30][31]. Although substantial efforts have been contributed to the construction of these polycyclic compounds [32][33][34][35][36][37][38][39], the CF 2 Mecontaining target polycycles remain a great challenge to date (Figure 1(2)). As part of our continuing interest in difluoroethylation functionalizations, we anticipated that the radical cyclization process would provide a feasible platform for the synthesis of CF 2 Merevised target polycycles.…”

The Peptide Bond: Resonance Increases Bond Order and Complicates Fragmentation

“…The fragment molecular orbital (FMO) method [15,16,17,18] has been developed for various QM methods such as Hartree‐Fock (HF) [15] and second order Møller‐Plesset perturbation theory (MP2), [19] and applied to a variety of biochemical [20,21,22,23] and inorganic [24,25] molecular systems.…”