Regio- and diastereoselective synthesis of N -substituted 2-acyl-3-aryl-3,5-dihydrofuro[3,2- c ]pyridin-4(2 H )-ones
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Regio- and diastereoselective synthesis of N-substituted 2-acyl-3-aryl-3,5-dihydrofuro[3,2-c]pyridin-4(2H)-ones Evgeny А. Kvetkin1, Dmitry V. Osipov1, Pavel E. Krasnikov1, Vitaly А. Osyanin1*, Yuri N. Klimochkin1 1
Samara State Technical University, 244 Molodogvardeyskaya St., Samara 443100, Russia; е-mail: [email protected] Submitted July 12, 2020 Accepted after revision August 3, 2020
Translated from Khimiya Geterotsiklicheskikh Soedinenii, 2020, 56(11), 1423–1428
The three-component condensation of pyridinium acylmethylides generated in situ with aromatic aldehydes and 4-hydroxy6-methylpyridones gave a series of 2-acyl-3-aryl-3,5-dihydrofuro[3,2-c]pyridin-4(2H)-ones. The reaction proceeds diastereoselectively with the formation of trans-isomers and represents a cascade process involving the Knoevenagel condensation, the carbo-Michael reaction, and intramolecular nucleophilic substitution. Keywords: 2-acyl-3-aryl-3,5-dihydrofuro[3,2-c]pyridin-4(2H)-ones, pyridinium ylides, MIRC reaction, multicomponent reactions.
The Michael-initiated ring-closure (MIRC) transformations1 are widely used for the preparation of cyclopropane derivatives from electron-deficient olefins and C-nucleophiles containing a good leaving group in their structure.2 Similar processes are used much less frequently for accessing heterocycles, in particular chromenoquinolines,3 derivatives of dihydrofurans,4 and their condensed analogs.5 Among the latter, 3,5-dihydrofuro[3,2-c]pyridin-4(2H)-ones are of great interest as key fragments of 4-hydroxy-2-pyridone alkaloids with a wide range of biological action,6 for example, citridone A,7 furopyridine antibiotic CJ-16,170,8 polyketide huaspenone D,9 and campyridone A10 (Fig. 1). Likewise, inhibitors of the mitochondrial complex I were described among the 4-hydroxy-2-pyridone alkaloids.11 In this work, we have shown that the reactions of 4-hydroxy-6-methylpyridones 1 with aromatic aldehydes 2 and pyridinium acylmethylides generated in situ from the corresponding pyridinium salts 3 leads to the formation of trans-2-acyl-3-aryl-3,5-dihydrofuro[3,2-c]pyridin-4(2H)-ones 4a–j in 54–79% yields (Scheme 1). The formation of cisisomers was not observed. The reaction was carried out in pyridine at 100°C in an argon atmosphere. Carrying out the 0009-3122/20/56(11)-1423©2020 Springer Science+Business Media, LLC
Figure 1. Alkaloids with the 3,5-dihydrofuro[3,2-c]pyridin4(2H)-one fragment.
1423
Chemistry of Heterocyclic Compounds 2020, 56(11), 1423–1428 Scheme 1
O Br– OH
+
O
O
N
CHO
O Ph Me
N Bn 4j
O
Py, 100°C, 8 h, argon Me – Py·HBr, – H2O 54%
+ O
N 1
1
2
R
R3
Br–
O R3
+
N
O
3
R2 Py, 100°C, 8 h, argon – Py·HBr, – H2O Me
N
O
R2
R1 4a–i
4 a R1 = R3 = Ph, R2 = H (57%); b R1 = R3 = Ph, R2 = 4-Cl (77%); c R1 = R3 = Ph, R2 = 4-MeO (64%); d R1 = 4-MeOC6H4, R2 = H, R3 = Ph (65%); e R1 = Ph, R2 = H, R3 = 3,4,5-(MeO)3C6H2 (70%); f R1 = 3,4-(MeO)2C6H3CH2, R2 = 2-NO2, R3 = Ph (75%); g R1 = pyridin-3-yl, R2 = H, R3 = Ph (68%); h R1 = 4-MeOC6H4, R2 = 4-Cl, R3 = 1-Ad (79%); i R1 = 4-MeOC6H4, R2 =
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