Studies on the Radical Cyclization of 3‐Oxopropanenitriles and Alkenes with Cerium(IV) Ammonium Nitrate in Ether Solvents

Abstract

The radical cyclization of 3-oxopropanenitriles 1a -1e and alkenes 2a -2g with cerium(IV) ammonium nitrate (CAN) in ether solvents was investigated (Tables 1 and 2). In the optimization study, 1,3-dioxolane, 1,4-dioxane, 1,2-dimethoxyethane, Et 2 O, and THF were used as ether-based solvents, and the latter was found to be the most effective solvent in radical cyclizations mediated by cerium(IV). This system (cerium(IV)/THF) was applied to cyclizations of various 3-oxopropanenitriles and 1,3-dicarbonyl compounds with alkenes resulting in the formation of 4,5-dihydrofurans in high yields ( Table 2 and Scheme 2). The results of the cerium(IV)/THF radical cyclization were compared with those obtained with manganese(III) acetate/AcOH; the cerium(IV)/THF system turned out to be much more efficient.Introduction. -During the last three decades, manganese(III) acetate dihydrate (MAH) [1] and cerium(IV) ammonium nitrate (CAN) [2] have been used as efficient radical oxidants. These oxidants have the ability for a one-electron transfer and are used in organic synthesis for constructing CÀC bonds. Both CAN and MAH are well known for dihydrofuran formation by radical cyclization of 1,3-dicarbonyl compounds with alkenes. Dihydrofurans show a wide range of biological activities and form the basic structure of many natural compounds [3].Our research group has studied the radical cyclization of 1,3-dicarbonyl compounds and 3-oxopropanenitriles with alkenes, alkynes, unsaturated amides, and dienes in the presence of manganese(III) acetate [4]. Very recently, we have reported that some 4,5-dihydrofuran-3-carbonitriles show antibacterial and antifungal activity [5]. These carbonitriles are available by oxidative cyclization of 3-oxopropanenitriles with conjugated alkenes [4f] [4g] and unsaturated amides [4h]. In these reactions, MAH/ AcOH gives good results, whereas CAN is not efficient when MeOH or MeCN are used as solvents. Hence, we performed an optimization using ether-based solvents and CAN which were more effective. We applied the optimized conditions (CAN/THF, 40 -608) to a study of the cyclization of 3-oxopropanenitriles and 1,3-dicarbonyl compounds with alkenes. Additionally, we compared cyclizations induced by CAN/THF and MAH/ AcOH. The CAN/THF method gave 4,5-dihydrofurans in high yields.

Synthesis of 5-membered heterocycles using benzoylacetonitriles as synthon

“…20 Regioselective synthesis of 2,3,4-trisubstituted pyrrole 10 has been achieved via [3,3] Three-component 1-pot condensation reactions of ethyl glycinate 11, 3-hydroxybutan-2-one 12, and 1 yielded ethyl 2-(3-cyano-4,5-dimethyl-2-phenyl-1H -pyrrol-1-yl)acetate 13, which was consequently hydrolyzed to produce the corresponding carboxylic acid 14 (Scheme 2). 9 4,5-Dihydro-3-furancarbonitrile derivatives 21 were obtained through radical cyclization of 1, mediated either by manganese(III) acetate in acetic acid 2,25,26 or by cerium(IV) ammonium nitrate in THF 27 with substituted ethylene 20. Cerium(IV)/THF radical cyclization was compared with that performed with manganese(III) acetate/AcOH; the cerium(IV)/THF system turned out to be much more efficient.…”

Synthesis of 2-(2-phenylethenyl) substituted 4,5-dihydrofurans by regioselective addition of 1,3-dicarbonyl compounds to dienes promoted by cerium(IV) ammonium nitrate

“…However, recently we performed an optimization study on the radical addition of 3-oxopropanenitriles to alkenes using CAN in ethereal solvents, resulting CAN / THF system formed dihydrofurans in high yields on mild condition. 42 In the present study, we applied the previous method to reactions of 1,3-dicarbonyl compounds with conjugated dienes promoted CAN / THF and obtained 2-(2-phenylethenyl) substituted 4,5-dihydrofurans as regioselectively in excellent yields.…”

Synthesis and characterization of piperazine-substituted dihydrofuran derivatives viaMn(OAc)3 mediated radical cyclizations

“…Manganese (III) acetate [29][30][31][32][33] and cerium(IV) ammonium nitrate (CAN) [34][35][36][37][38] are widely used in these reactions. Our research group has reported radical addition and cyclization reactions with CAN [39][40][41][42] and radical cyclization reactions of 1,3-dicarbonyl derivatives with various unsaturated systems, such as conjugated amide derivatives [43][44][45][46][47]and heteroaromatic conjugated alkenes [48][49][50][51].…”