Elimination of nitriles in retro-diene reactions

Cyanide‐Free Cyanation of sp2 and sp‐Carbon Atoms by an Oxazole‐Based Masked CN Source Using Flow Microreactors

“…After installing the masked nitrile source ( 2 a ) into the aryl, vinyl and acetylenic halides, we further investigated the reaction condition required to demask the oxazole substructure from product ( 4 a – 4 p ) in order to provide a rapid and efficient access to the desired nitrile derivatives. Based on literature evidences, [16] we investigated possibility to use the azabutadiene system in oxazole 4 a with acetylenic dienophiles. Further, [4+2]/retro‐[4+2] sequence was validated in batch by heating 5‐methyl‐2,4‐diphenyloxazole ( 4 a ) and diethyl acetylenedicarboxylate (5 equiv.)…”

“…[15] Therefore, it is desirable to develop a novel versatile chemical route for cyanation/CÀ CN bond formation from a single, non-poisonous and stable cyanide source with an easy access to incorporate cyano groups at either of carbons (sp 2 / sp). In an attempt to develop a complementary cyanation strategy, obviating the need for direct or transient use of cyanide, there are scarce reports using oxazoles where nitriles were generated as a byproduct during the synthesis of substituted furans, pyrimidines, [16] and aliphatic ω-cyano acids [17] which was largely ignored. Later, few reports in this direction demonstrated isoxazole-4-boronic acid pinacol ester [18] as well as 4-bromo-5-methyl-2-phenyloxazole [19] as a potential masked source for acetonitrile anion equiv., however limiting its substrate scope only to cyanomethylation reaction on aromatic substrates and for olefin hydrocyanation.…”

Stereoselective Synthesis of 2-Aryltetrahydrofuran-3,4-dicarboxylate Derivatives: Efficient Approach to Tetrahydrofuran Lignans

“…The preparation of heterocyclic compounds utilizing 1,3,4-oxadiazole and oxazole compounds through a tandem Diels-Alder reaction and reverse Diels-Alder reaction has been investigated. [14][15][16][17][18][19][20] Furan compounds can be prepared in high yields through the reaction Scheme 1 of oxadiazoles with alkenes or alkynes that contain angle strain or are electron-rich. 21 Initially, substituted 1,3,4-oxadiazoles were selected as diene because they are easily prepared.…”

Mesoionic compounds. 47. Cycloadditions with the 4(5H)-oxazolone system

“…An alternative route involves Diels-Alder addition of DMAD to the 4-hydroxyoxazole tautomer 3c, oxazoles having been shown to act in this fashion giving furans after extrusion of a nitrile from the initial 1:1 adduct. 7 The latter route appears unlikely as the 5(4/7)-oxazolones were shown not to react in this fashion2 and in the 4(5/7)-thiazolones, the 4-alkoxy-and 4acetoxythiazoles did not undergo cycloaddition under reaction conditions successful with the unblocked thiazolones.…”

“…A solution of 2-phenyl-4(5//)-oxazolone12 (0.8 g, 0.005 mol) and DMAD (2.5 mL) in acetic anhydride (5 mL) was heated at 130 °C for 18 h. The volatile components were removed in vacuo and the residue taken up in benzene and chromatographed (silica gel, 75 g, eluted with Et20petroleum ether, 2:3) to afford as the only isolable component dimethyl 2-phenylfuran-3,4-dicarboxylate (5; R = Ph; R1 = COOCH3), 0.32 g (26%). It crystallized from CH3OH as colorless plates: mp 70-71 °C; IR (KBr) 3170, 3030, 2980 (CH), 1730, 1720 (CO) cm-1; Xmax (CH3OH) 259 nm (log r 3.34); NMR (CDC13) 7.89 (s, 1, Cs-H), 7.16-7.84 (m, 5, phenyl), 3.82 In a similar fashion 2-(4-chlorophenyl)-4(5//)-oxazolone (1.0 g, 0.005 mol), DMAD (2.5 mL, ca. 0.02 mol), and Ac20 (7 mL) were heated at 130 °C for 18 h. The volatile components were removed by evaporation and the residue chromatographed (silica gel, 40 g, eluted with Et20-petroleum ether 1:1) to give as the first component dimethyl 2-(4-chlorophenyl)furan-3,4-dicarboxylate (5, R = p-ClCeH4; R1 = COOCH3) crystallizing from CH3OH as fine colorless needles: 0.43 g (29%); mp 93-93.5 °C; IR (KBr) 1760, 1735 (CO) cm-1; Xmax (CH3OH) 278 nm (log e 4.24); NMR (CDCI3) 7.97 (C5-H), 7.61 (d, 2, aromatic), 7.32 (d, A second fraction crystallized from CH3OH to afford tetramethyl 1-(4-chlorophenyl)-7-oxabicyclo [2.2.1 ] hepta-2,5-diene-2,3,5,6-tetracarboxylate (6, R = p-ClCgH^a s colorless irregular prisms: 0.42 g (19%); mp 126-127 °C; IR (KBr) 1753,1735 (CO) cm"1; Xmax (CH3OH) 332 nm (log e 3.69), 224 (4.15); NMR (CDC13) 7.42 (s, 4, aromatic), 6.10 (s, 1. bridgehead CH), 3.80 (b, 12, CH3); M+-377 (6), 294 (100).…”