Donor–Acceptor Cyclopropanes as an Expedient Building Block Towards the Construction of Nitrogen‐Containing Molecules: An Update

Abstract

Nitrogen‐containing molecules are the key structural constituent of many pharmaceutical compounds that play a pivotal role in drug development. Owing to their multifaceted medicinal importance, several synthetic approaches have been delineated in the recent past for their construction. Over the past few decades the augmented use of donor–acceptor cyclopropanes (DACs) as three‐carbon synthetic equivalents, despite their ring strain, for the construction of innumerable hetero‐ and carbocycles of pharmaceutical importance has raised the interest of synthetic chemists to this topic. Owing to their zwitterionic nature due to the vicinal disposition of donor and acceptor groups, they have been frequently used in ring‐opening reactions, cycloadditions, and rearrangements. This review is mainly focused on assorted reactions of DACs with various nitrogen‐containing dipolarophiles like imines, azides, cyanates, isothiocyanates, nitrosocarbonyls, hydrazines, diaziridines, triazinanes, diazenes, etc. towards the synthesis of nitrogen‐containing molecules of pharmaceutical and industrial importance. This review is in continuation of our review published in the Israel Journal of Chemistry in April 2016, and includes the literature from April 2016 to May 2019.

Research Progress of 1,3,5-Triazinanes in the Synthesis of Nitrogen-Containing Heterocycles

“…Donor-Acceptor (D-A)环丙烷在 Lewis 酸作用下, 常 常作为 1,3-偶极子, 通过[3＋n]环化反应模式, 参与环 状化合物的构建 [12][13][14][15][16] . 2017 年, Werz 课题组 [17] 报道了一 种镁催化 D-A 环丙烷 8 和 1,3,5-三嗪烷 1 合成 2-取代吡 作者只研究了苯基以及对甲氧基苯基取代 D-A 环丁烷 的反应情况, 反应结果表明, 对甲氧基苯基取代环丁烷 的产率(67%～75%)要优于苯基取代环丁烷(56%).…”

Dioxin and dibenzofuran like molecular analogues from the pyrolysis of biomass materials—the emerging challenge in bio-oil production

“…4 and 5 and Additional file 1: Figures S3 and S4, are unique because they are not formed when tyrosine is pyrolyzed individually [18] or when cellulose is pyrolyzed alone under similar conditions as applied in this work. This can only explain two scientific proposals; i.e., firstly, tyrosine or any model amino acid inhibits the formation of chemicals of interest for bio-oil production, and secondly, cellulose in presence of amino acids acts as a catalyst for the formation of nitrogenated chemicals, which are suggested as intermediates for drug and polymer manufacture [39,40], in addition to the fact that they are emerging environmental pollutants having similar toxicological characteristics as polychlorinated dioxins and polychlorinated dibenzofuran analogues [37]. Therefore, this study has made some ground breaking informative findings towards the synthesis of intermediates of medical value and also offers direction against the inclusion of amino acids in lignocellulosic components during the production of biooil.…”

Functionalized Cyclopropanes as Versatile Intermediates for the Diversity-Oriented Synthesis of γ-Lactones, γ-Lactams and δ-Lactams

“…IR (KBr): 3070, 2984, 1726, 1526, 1444, 1346, 1203, 1132, 1024, 787 cm -1 1. H NMR (400 MHz, CDCl 3 ):  (trans isomer) = 7.92 (dd, J = 8.2, 1.0 Hz, 1 H, CH Ar ), 7.64-7.36 (m, 3 H, CH Ar ),7.15 (d, J = 15.6 Hz, 1 H, =CH), 5.84 (dd, J = 15.6, 8.8 Hz, 1 H, =CH), 4.32-4.14 (m, 4 H, OCH 2 ), 2.65-2.58 (m, 1 H, CH), 1.82 (dd, J = 7.2, 5.2 Hz, 1 H, CH 2 ), 1.72 (dd, J = 9.0, 5.2 Hz, 1 H, CH 2 ), 1.30 (t, J = 7.2 Hz, 3 H, CH 3 ), 1.26 (t, J = 7.2 Hz, 3 H, CH 3 ). 1 H NMR (400 MHz, CDCl 3 ):  (cis isomer) = 8.08 (dd, J = 8.2, 1.0 Hz, 1 H, CH Ar ), 7.64-7.36 (m, 3 H, CH Ar ), 6.92 (d, J = 11.2 Hz, 1 H, =CH), 5.39 (dd, J = 11.2, 10.0 Hz, 1 H, =CH), 4.32-4.14 (m, 4 H, OCH 2 ), 2.82-2.76 (m, 1 H, CH), 1.76 (dd, J = 7.4, 4.8 Hz, 1 H, CH 2 ), 1.60 (dd, J = 9.0, 4.8 Hz, 1 H, CH 2 ), 1.31 (t, J = 7.2 Hz, 3 H, CH 3 ), 1.26 (t, J = 7.2 Hz, 3 H, CH 3 ).13 C NMR (100 MHz, CDCl 3 ):  = 169.3 (C), 169.2 (C), 167.6 (C), 167.5 (C), 148.1 (C), 147.6 (C), 133.1 (2 × CH), 132.4 (C), 132.2 (C), 132.1 (CH), 131.0 (CH), 129.6 (CH), 129.1 (CH), 128.6 (CH), 128.49 (CH), 128.47 (CH), 128.2 (CH), 124.9 (CH), 124.7 (CH), 61.9 (CH 2 ), 61.83 (2 × CH 2 ), 61.77 (CH 2 ), 36.7 (C), 36.5 (C), 31.0 (CH), 27.4 (CH), 22.3 (CH 2 ), 21.3 (CH 2 ), 14.33 (CH 3 ), 14.29 (CH 3 ), 14.2 (2 × CH 3 ).…”