Transition Metal-Participated Synthesis and Utilization of N-containing Heterocycles: Exploring for Nitrogen Sources

Abstract

This account aims to describe our recent efforts on the synthesis and utilization of N-containing heterocycles, where transition metals participate in the synthesis. A variety of nitrogen sources, including amines, amides, hydrazones, pyrimidines, isocyanides, and copper nitrate, have been disclosed for the synthesis of diverse bioactive and pharmacologically interesting N-containing heterocycles under the participation of transition metals. The well-known nitrogen sources, such as amines and amides, were used for the construction of indoles, isatins, and quinolones. Dihydrophthalazines, isoquinolines, indazoles, and pyrazoles were obtained from hydrazones, while various pyrimidine-containing heterocycles were afforded through regioselective C-H functionalizations using pyrimidine as the directing group. Recent research has focused on the chemistry of isocyanides to achieve several kinds of heterocyclic compounds with high efficiency under the catalysis of transition metals (Pd, Rh, Mn, Cu), through oxidative cyanation reactions, sequential isocyanide insertions into C-H, N-H, or O-H bonds, and tandem radical annulation. More recently, an efficient route to isoxazolines has been reported using copper nitrate as a novel nitrogen source.

Recent Advances in Indazole-Containing Derivatives: Synthesis and Biological Perspectives

“…The nitrogen-containing heterocycles are important building blocks for many bioactive natural products and commercially available drugs. As pharmacologically important scaffolds, they have attracted considerable attention from chemists [ 1 ]. Indazoles are one of the most important classes of nitrogen-containing heterocyclic compounds bearing a bicyclic ring structure made up of a pyrazole ring and a benzene ring.…”

Hypervalent iodine(iii)-mediated oxidative dearomatization of 2H-indazoles towards indazolyl indazolones

“…N-containing heterocyclic scaffolds are extremely privileged structures because of their wide ranging biological and pharmacological activities. 1 Among these, indazole (a pyrazole ring fused with a benzene ring), which belongs to the azole family, is a popular core structure in many pharmacophores. Indazole derivatives are of paramount importance in agrochemical, biological and industrial fields.…”

A novel Pd-catalysed sequential carbonylation/cyclization approach toward bis- N -heterocycles: rationalization by electronic structure calculations

“…Of all the known nitrogen-bearing heterocycles, those containing an indole scaffold hold special relevance in synthetic organic chemistry [1][2][3][4]. Scientific interest in this family of alkaloids stems from a number of factors, including their bioactivity and biomedical applications [4][5][6].…”

“….4.3. (4aS,8aR)-3-(1H-indol-7-yl)-4a,5,6,7,8,8a-hexahydroquinoxalin-2(1H )-one (2b) R f (70% EtOAc, 30% n-hexane) 0.58; brown solid: 27 mg, 20% yield; mp 180-1848C;1 H NMR (CDCl 3 , 400 MHz): d ( ppm) ¼ 10.96 (s, 1H), 8.40 (d, J ¼ 7.6 Hz, 1H), 7.78 (d, J ¼ 7.8 Hz, 1H), 7.30 (t, J ¼ 7.8 Hz, 1H), 7.17 (t, J ¼ 7.8 Hz, 1H), 7.15 (br s, 1H), 6.60 (t, J ¼ 8.4 Hz, 1H), 4.12 -4.05 (m, 1H), 3.71 (br s, 1H), 2.01-1.90 (m, 1H), 1.86 (br s, 1H), 1.78-1.65 (m, 3H), 1.65-1.54 (m, 1H), 1.46 (m, 2H); 13 C NMR (CDCl 3 , 100.6 MHz): d ( ppm) ¼ 160.8, 158.5, 134.9, 128.9, 125.9, 124.5, 124.5, 119.1, 117.3, 102.6, 57.6, 49.0, 29.8, 28.6, 22.6, 21.3; IR (KBr, n (cm 21 )): 3350, 3177, 1679; HRMS (ESI) m/z: calcd for C 16 H 17 N 3 O [M þ H] þ 268.1444; found: 268.1442. ¼ 11.04 (br, 2H), 8.46 (d, J ¼ 7.6 Hz, 2H), 8.27 (br, 2H), 7.99 (d, J ¼ 7.8 Hz, 2H), 7.49 (d, J ¼ 8.8 Hz, 2H), 7.19 (td, J ¼ 7.7, 2.6 Hz, 2H), 6.63 (d, J ¼ 2.4 Hz, 2H), 3.66 -3.52 (m, 4H), 2.01 -1.95 (m, 1H), 1.82 -1.75 (m, 1H); 13 C NMR (acetone-d6, 100.6 MHz): d ( ppm) ¼ 190.7, 165.3, 136.0, 130.9, 129.4, 129.2, 127.7, 119.6, 117.8, 103.3, 37.2, 32.7; IR (KBr, n (cm 21 )): 3392, 3276, 1663, 1633; HRMS (ESI) m/z: calcd for C 23 H 20 N 4 NaO 4 þ [M þ Na] þ 439.1377; found 439.1377.…”

“…R f (75% CHCl 3 , 25% EtOAc) 0.26; dark red solid: 25 mg, 15% yield; mp 100-1028C;1 H NMR (TMS, 400 MHz): d ( ppm) ¼ 9.42 (sl, 1H), 7.70 (d, J ¼ 7.8 Hz, 1H), 7.27 -7.21 (m, 2H),7.08 (t, J ¼ 7.6 Hz, 1H), 6.54 (dd, J ¼ 3.1, 2.2 Hz, 1H), 3.16 (s, 6H);13 C NMR (CDCl 3 , 100.6 MHz): d ( ppm) ¼ 170.7, 134.9, rsos.royalsocietypublishing.org R. Soc. open sci.…”