Synthesis of 1,3-Benzodiazepines through [5 + 2] Annulation of N-Aryl Amidines with Propargylic Esters

Abstract

In this paper, an efficient synthesis of functionalized 1,3-benzodiazepines through an unprecedented [5 + 2] annulation of N-aryl amidines with propargylic esters is presented. The reactions proceed through Rh­(III)-catalyzed C­(sp2)−H alkenylation followed by annulation and deacetoxylation along with cascade C−H/N−H/C−O bond cleavage and C−C/C−N bond formation. Furthermore, the cytotoxicity of selected products against several human cancer cell lines was tested, which demonstrated their good potential for pharmaceutical applications.

Synthesis of spirocyclopropylpyrazole derivatives via the cascade reaction of alkylidenecyclopropanes with pyrazolidinones and trifluoroethanol

“…Finally, the synthetic applications of the spirocyclopropylpyrazole products obtained above were explored. [11][12][13] First, 4aa was treated with DIBAL-H in DCM at 0 °C to give its alcohol derivative 5 in 88% yield (Scheme 7). Second, 4aa was treated with NaOH (6 M) and then HCl (2 M) to afford the corresponding carboxylic acid derivative 6.…”

Synthesis of Dihydroquinolinone Derivatives via the Cascade Reaction of o-Silylaryl Triflates with Pyrazolidinones

“…Synthesis of 7. 21 To a reaction tube equipped with a stir bar were added 3i (27.6 mg, 0.08 mmol), ethynylbenzene (13 μL, 0.12 mmol), PPh 3 (4.2 mg, 0.016 mmol), K 3 PO 4 (20.4 mg, 0.096 mmol), Pd(OAc) 2 (0.9 mg, 0.004 mmol), and DMSO (1 mL). The resulting mixture was stirred at 80 °C (oil bath) for 24 h under an argon atmosphere.…”

Open-Air Dual-Diamination of Aromatic Aldehydes: Direct Synthesis of Azolo-Fused 1,3,5-Triazines Facilitated by Ammonium Iodide

“…Buchwald, Deng, Zhang, Wu, Zhu, Xu, and Hwang described some elegant [5 + 1] annulations of N -arylamidines with aldehydes, DMSO, sulfoxonium ylides, cyclopropenones, isonitriles, or terminal alkynes to obtain quinazolines . Furthermore, Fan and co-workers found a [5 + 2] annulation of N -aryl amidines with propargylic esters to produce 1,3-benzodiazepines . In addition, the Ma team presented an oxidative annulation of N -arylamidines with N , N -dimethylethanolamine as a C1 synthon to construct a 1,2-dihydro-1,3,5-triazine skeleton .…”

“…9 Furthermore, Fan and co-workers found a [5 + 2] benzodiazepines. 10 In addition, the Ma team presented an oxidative annulation of N-arylamidines with N,N-dimethylethanolamine as a C1 synthon to construct a 1,2-dihydro-1,3,5triazine skeleton. 11 Inspired by the high reactivity exhibited by N-aryl amidines, we hypothesize that simple aldehydes are capable of efficiently accomplishing the first diamination with 3-aminoazoles and a nitrogen source to generate in situ Nazolo amidines and accelerating the implementation of the second diamination.…”