A Zinc-Mediated Deprotective Annulation Approach to New Polycyclic Heterocycles

Abstract

A straightforward approach to new polycyclic heterocycles, 1H-benzo[4,5]imidazo[1,2-c][1,3]oxazin-1-ones, is presented. It is based on the ZnCl2-promoted deprotective 6-endo-dig heterocyclization of N-Boc-2-alkynylbenzimidazoles under mild conditions (CH2Cl2, 40 °C for 3 h). The zinc center plays a dual role, as it promotes Boc deprotection (with formation of the tert-butyl carbocation, which can be trapped by substrates bearing a nucleophilic group) and activates the triple bond toward intramolecular nucleophilic attack by the carbamate group. The structure of representative products has been confirmed by X-ray diffraction analysis.

A Ag2CO3/TFA-catalyzed intramolecular annulation approach to imidazo[1,2-c][1,3]oxazin-5-one derivatives

“…In order to prepare a library of new imidazo[1,2- c ][1,3]oxazin-5-one heterocycles, N -Boc-4-bromo-5-methyl-2-phenylethynylimidazole 1a was studied as a model substrate and subjected to some annulation process conditions which have been already described in the literature. 25,37,46,49,50,57–64 Compound 1a , which is a suitable substrate for undergoing intramolecular annulation, was prepared following our recent procedure involving the regioselective Sonogashira cross coupling reaction of N -Boc-2,5-dibromo-4-methylimidazole. 48 Initially, the zinc catalyst (ZnCl 2 ) was used in dichloromethane at 40 °C but it was found to be totally inert since the starting material was completely recovered after 48 h (Table 1, entry 1).…”

“…1g). 50 Considering the importance of developing efficient catalytic approaches for the synthesis of new heterocycles, we report herein a silver-catalyzed intramolecular oxacyclization of N -Boc-2-alkynyl-4-bromo(alkynyl)-5-methylimidazole 1 to form new 3-methylimidazo[1,2- c ][1,3]oxazin-5-one derivatives 2 (Fig. 1h).…”

Organic Synthesis via Transition Metal-Catalysis

“…The subsequent papers report on transition-metal-promoted cyclization processes leading to heterocyclic derivatives. Thus, new polycyclic heterocycles (1H-benzo [4,5]imidazo[1,2c][1,3]oxazin-1-ones) were synthesized by Lucia Veltri, Roberta Amuso, Marzia Petrilli, Corrado Cuocci, Maria A. Chiacchio, Paola Vitale, and Bartolo Gabriele using a ZnCl 2promoted deprotective annulation approach starting from N-Boc-2-alkynylbenzimidazoles under mild conditions (CH 2 Cl 2 as the solvent at 40 • C for 3 h) [6]. N-benzoylindoles were obtained by Zhe Chang, Tong Ma, Yu Zhang, Zheng Dong, Heng Zhao, and Depeng Zhao by Pd(II)-catalyzed oxidative C-H functionalization and annulation of substituted N-(2allylphenyl)benzamides, carried out with Pd(OAc) 2 as the catalyst in the presence of benzoquinone as the oxidant and dibutyl phosphate as the additive in DMSO at 60-70 • C [7].…”