Base-promoted cyclization of 3-alkynylquinoxaline-2-carbonitriles with CH-acids: a new method for the phenazine ring synthesis

• Published in: Tetrahedron Vol. 70; no. 31; pp. 4617 - 4625
• Main Authors: Nguyen, Huong T.L., Gulevskaya, Anna V., Pozharskii, Alexander F., Nelina-Nemtseva, Julia I.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 05.08.2014; Elsevier
• Subjects: 3-Alkynylquinoxaline-2-carbonitriles; Bonding; Cascade cyclization; Cascades; Chemistry; Chemistry, Organic; Formations; Malononitrile; Nitromethane; Nucleophilic cyclization; Phenazines; Physical Sciences; Science & Technology; Synthesis (chemistry); Tetrahedrons; PVSNGZLJYYWFSQ-UHFFFAOYSA-N; NUFZHUHUKWZBMF-UHFFFAOYSA-N; ACGWWVBYERXMNA-UHFFFAOYSA-N; COEHCXRVFHZYIK-UHFFFAOYSA-N; JFQLEADIZHZJKU-UHFFFAOYSA-N; Nucleophilic cyclization; ULHKCNUOXJRGNA-UHFFFAOYSA-N; RFMGZILSPAPMLW-UHFFFAOYSA-N; WQUQQPPGYNWWHI-UHFFFAOYSA-N; UABALGSTEAEZPV-UHFFFAOYSA-N; GUOZVFJAEGIKLS-UHFFFAOYSA-N; OEVCJXMBNAEGLU-UHFFFAOYSA-N; Cascade cyclization; PEWRKUYHXSMCTL-UHFFFAOYSA-N; CXJSEOSWNBHPQY-PYCFMQQDSA-N; YHMZEEGZUJYFGW-UHFFFAOYSA-N; PTHGTEXVACDPPA-UHFFFAOYSA-N; 3-Alkynylquinoxaline-2-carbonitriles; Phenazines; IYJOIGYBSYWEJF-UHFFFAOYSA-N; JPKDBTTUPARANI-UHFFFAOYSA-N; BIOSYNTHESIS
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2014.05.023

3-Alkynylquinoxaline-2-carbonitriles were directly transformed into 2,3-disubstituted phenazin-1-amines by treating with a CH-acid (diethylmalonate, ethyl cyanoacetate, malononitrile, 2-tosylacetonitrile, 2-(1-methyl-1H-benzo[d]imidazol-2-yl)acetonitrile, nitromethane) and t-BuOK in THF or DMSO. A new cascade process includes nucleophilic addition of a CH-acid carbanion to the CC bond of 3-alkynylquinoxaline-2-carbonitrile, 6-exo-dig cyclization of the intermediate allyl carbanion with the formation of 2,2-disubstituted 1-imino-1,2-dihydrophenazine and its aromatization via elimination of the C(2)-substituent. Several secondary reactions were also disclosed and discussed. [Display omitted]