1,2-Addition to trifluoromethylated β-enamino diketones: regioselective synthesis of trifluoromethyl-containing azomethine pyrazoles and isoxazoles

Abstract

Trifluoromethylated β-enamino diketones undergo type 1,2-addition leading to regioselective synthesis of trifluoromethylated azoles containing an azomethine group.

The Wonderful World of β‐Enamino Diketones Chemistry

“…With knowledge of the selectivity issues found for the reaction of β‐enamino diketones and hydroxylamine hydrochloride, trifluoromethyl isoxazole derivatives were prepared in a later work. [ 34 ] This was achieved by reacting β‐enamino diketones 2 with tert ‐butylamine to furnish β‐enamino diketones 9 , which were readily reacted with hydroxylamine hydrochloride with the addition of BF 3 (OEt) 2 in refluxing MeCN for 5 h. In a one‐pot procedure, the formyl moiety was treated with arylamines to furnish, at 63–81 % yields, the trifluoromethyl isoxazole derivatives 10 containing an imine moiety as a single isomer (Scheme 5).…”

“…[ 52–55 ] Using a similar approach, trifluoromethyl β‐enamino diketones 9 were used in a regio‐ and chemoselective cyclocondensation reaction with phenylhydrazine (Scheme 12). [ 34 ] The corresponding pyrazoles 29 were obtained in refluxing MeCN for 7 h (with addition of BF 3 (OEt) 2 ), at moderate to good yields (60–84 %). Interestingly, when β‐enamino diketone 4 was used, the hydrolysis of the imine group (to furnish the formyl moiety) was not observed as previously reported.…”

“…[ 45 ] Through a transimination reaction, several examples derived from arylamines were prepared at moderate yields (54–78 %); however, it is important to highlight that arylamines bearing strong electron‐withdrawing groups (4‐NO 2 or 3,4‐(CF 3 ) 2 ) did not lead to the final product 30 (Scheme 12). [ 34 ]…”

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

“…[ 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.…”