Recent advances in transition metal-free annulation toward heterocycle diversity based on the C–N bond cleavage of enaminone platform

Abstract

The enaminones and analogous stable enamines are well known as platform building blocks in organic synthesis for construction of heterocyclic compounds, especially N-heterocycles. To date, especially enaminones have been successfully...

Synthesis of 2-Aminofurans and 2-Aminothiophenes through Elemental Sulfur-Promoted Switchable Redox Condensation Reaction of Enaminones with Methylene Nitriles

“…The obtained product was a red solid (75% yield, 81 mg, V Petroleum ether /V Ethyl acetate = 2.5:1, R f = 0.4); mp 64.5− 64.7 °C; IR (KBr): 3457,3342,2976,22354,1726,1682,1554,1470,1375,1331,1252,1097,816, 694 cm −1 ; 1 H NMR (500 MHz,DMSOd 6 ): δ 8.45 (s, 1H), 7.67 (d,J = 9.8 Hz,2H),7.56 (s,2H),7.38 (d,J = 8.2 Hz,2H), 4.30 (m, J = 7. 1 Hz,2H),2H), 1.29 (t, J = 6.7 Hz, 3H), 1.23 (t, J = 7.0 Hz, 3H); 13 66 mg, V Petroleum ether /V Ethyl acetate = 2.5:1, R f = 0.4); mp 64.5−64.9 °C; IR (KBr): 3447,3352,2294,2958,2235,1722,1682,1634,1550,1374,1256,1012,847,702 d,J = 21.3 Hz),115.5,114.8,112.5,112.3,108.8,87.9,62.8,59.8,14.6,14.4;19 Ethyl (E)-2-Amino-4-(2-cyano-3-ethoxy-3-oxoprop-1-en-1-yl)-5-(m-tolyl)furan- 3-carboxylate (3j). Synthesize...…”

“…The obtained product was a red solid (69% yield, 67 mg, V Petroleum ether /V Ethyl acetate = 2.5:1, R f = 0.4); mp 123. 1− 123.4 °C;IR (KBr): 3477, 3340, 2981, 2234, 1728, 1517, 1464, 1378, 1262, 1104, 1023, 780 cm −1 ; 1 H NMR (500 MHz, acetone-d 6 ): δ 8.39 (d, J = 2.5 Hz, 1H), 7.34−7.26 (m, 3H), 6.87 (s, 2H), 4.21 (q, J = 7.2 Hz, 2H), 4.12 (q, J = 7.2 Hz, 2H), 1.23− 1.19 (m, 3H), 1.18−1.15 (m, 3H); 13 3,12.3 Hz),148.0,140.8,127.2 (dd,J = 7.1,3.8 Hz), 122.9 (dd, J = 6.5, 3.5 Hz), 118.2 (d,J = 17.5 Hz),116.4,114.8 (d,J = 18.8 Hz),114.1,109.3,88.7,62.2,59.6,13.7,13.5;19 Ethyl (E)-2-Amino-4- (2-cyano-3-ethoxy-3-oxoprop-1-en-1-yl)-5- (3,4-dimethoxyphenyl)furan-3-carboxylate (3m). Synthesized according to general procedure 1.…”

“…Nevertheless, the annulation reaction of nucleophilic site C2 and electrophilic site C3 is seldom documented (Scheme a) . Especially, the cascade annulation reactions of the weak nucleophilic site O5 remains a considerable challenge as it is relatively difficult to control regarding chemoselectivity and/or regioselectivity (Scheme a).…”

“…12 Nevertheless, the annulation reaction of nucleophilic site C2 and electrophilic site C3 is seldom documented (Scheme 1a). 13 Especially, the cascade annulation reactions of the weak nucleophilic site O5 remains a considerable challenge as it is relatively difficult to control regarding chemoselectivity and/or regioselectivity (Scheme 1a). In the 2010s, the Park group and the Al-Matar group reported 2,3-annulation of enaminone with diazoesters and nitrile ethyl esters to obtain 2-aminofurans 14 and 2-aminothiophenes, 15 respectively (Scheme 1b).…”

The Suzuki–Miyaura Cross-Coupling–Claisen Rearrangement–Cross-Metathesis Approach to Prenylated Isoflavones

“…60 Four 3-iodochromones 14 were synthesized as platform starting materials for the Suzuki coupling reactions. The syntheses proceeded in two steps starting from ortho-hydroxy acetophenones 11, which were treated with DMF−dimethylacetal in DMF as a solvent to furnish enamino ketones 61 12. Enaminones 12 were then converted to the desired 3iodochromones 14 by reaction with iodine in methanol at ambient temperature (Table 1).…”