Development of methodologies for the regioselective synthesis of four series of regioisomer isoxazoles from β-enamino diketones

Abstract

Efficient and regioselective synthesis of isoxazoles was demonstrated through cyclocondensation of β-enamino diketones with hydroxylamine: four of the six possible regioisomers were obtained.

The Wonderful World of β‐Enamino Diketones Chemistry

“…The reaction of β‐enamino diketones 3 with hydroxylamine hydrochloride furnishes di‐ or tri‐substituted isoxazoles in regioisomeric mixtures, depending on the condition applied (Scheme 4). [ 33 ] By using simple additives such as pyridine or BF 3 (OEt) 2 , and depending on the choice of solvent (EtOH or MeCN) and temperature, the authors were able to control the reaction well, favoring one of the isomers formed for each case (products 6–8 , Scheme 4). Even though the reaction is not fully regioselective, the major isomers were isolated in their pure form after column chromatography, at 50–74 % yields.…”

Divergent and Regioselective Synthesis of (Trifluoromethyl/carboxyethyl)benzo[4,5]imidazo[1,2‐a]pyrimidines from β‐Enamino Diketones

“…[ 18 ] To overcome the selectivity issue, β‐enamino diketones (see Scheme 1) have emerged as suitable starting materials for the synthesis of several heterocyclic scaffolds, due to presenting high selectivity in most of the cyclocondensation reactions performed. [ 19–21 ] Even though the chemistry of carboxyethyl β‐enamino diketones 1 has been explored, [ 22–29 ] trifluoromethyl 2 ones have been far less used in heterocyclic synthesis. [ 21,30–34 ] Thus, this work aims to study the cyclocondensation reaction between β‐enamino diketones ( CCC building blocks) and 2‐aminobenzimidazole ( NCN ‐dinucleophile), observing the regioselectivity of the obtained products.…”

Trifluoromethyl β‐Enamino Diketones as Dual Substrates for the Synthesis of 5‐Benzoyl‐6‐(trifluoromethyl)pyrimidines and their Pyrimidin‐4(3H)‐one Analogues

“…ever, a NN-dinucleophile (hydrazine) provides a mixture of products from sites 1 and 2, as well as a mixture of their isomers. [21] These 1,3-diketones 1 have been shown to be suitable starting materials for preparing several nitrogenated heterocycles such as pyrazoles, [22,23] isoxazoles, [24] triazolopyrimidines, [20] and other aza-heterocycles. [25] Scheme 1.…”

“…Hz, J = 0.6 Hz 1H, Ar), 7.67 (dd, J = 1.6 Hz, J = 0.7 Hz, 1H, Ar)8.03 (s 1H, H4), 9.09 (s, 1H, OH).13 C NMR (100 MHz, CDCl 3 ): δ 14.6 (SMe), 46.8 (C7), 84.5 (q, 2 J C-F = 33.9 Hz, C6), 106.2 (C5), 112.9 (Ar), 118.0 (C9), 122.9 (Ar), 124.2 (q, 1 J C-F = 293.9 Hz, CF 3 ), 133.1(C8), 146.9 (Ar), 150.9 (Ar), 151.9 (C4), 167.5 (C2), 183.7 (C=O). GC-MS (EI, 70 eV): m/z (%) 346 (1), 277 (66), 278 (10), (72), 289(38), 275 (52), 261(12), 181(24), 135 (100), 92(14), 77(19). Anal.…”