Cerium(IV)oxidations, Part IX: Cyclization of Diethyl 4‐Phenylbutane‐1, 1‐dicarboxylate

Abstract

The oxidative cyclization of N-benzyl-P-aminoketones using cerium(1V)sulphate is a valuable method for the synthesis of various substituted 1,2,3,4-tetrahydroiso-q~inolines*-~). Investigations of the reaction mechanism showed the formation of an oxoalkyl radical in the first step followed by a radical aromatic substitution. In order to gain more insight into the mechanism of the oxidative cyclization we extended our investigations to nitrogen-free systems such as diethyl 4-phenylbutane-1,1 -dicarboxylate (1).Methyl acetoacetate and acetylacetone6) give ESR signals charaFteristic of the corresponding oxoalkyl radicals R-C(CS=O)~ (measured in a flow cell in sulfuric acid in the presence of cerium(IV)sulphate, go = 2.01 56 and 2.0052, respectively). Therefore, it is probable that the phenylbutane dicarboxylate 1 will also form an oxoalkyl radical which is able to attack the phenyl ring forming a tetrahydronaphthalene derivative. Due to the poor solubility of 1 in sulfuric acid the reaction was performed in glacial acetic acid using cerium ammonium nitrate (CAN).First oxidations of diethyl 4-phenylbutane-l , 1 -dicarboxylate (1) were carried out in glacial acetic acid containing 0.3% water at 80°C and a molar ratio of substrate/CAN = 1:2. The reaction was terminated after 3 h by addition of water. Four derivatives could be isolated from the reaction by means of column chromatography, and the structures were elucidated by 'H-NMR, I3C-NMR and mass spectroscopic data: The expected cyclization product 2, a nitro derivative 4, and an alcohol 3 as well as the corresponding acetate 5 (Scheme 1). In contrast to other CAN-oxidations of comparable compounds, e.g. esters of 5-aryl-3-oxopentanoic acids'), no n i t r e derivative was obtained.The structure of the nitro product 4 has been assigned by means of EI-MS and IR-spectra: The loss of 46 mu observed in El-MS results from a loss of NO2 proved by high resolution measurement of this peak. No loss of NO was observed. These data exclude a R-0-N=O structure whose formation is also likely during the reaction. A further hint for the R-N02 structural element is the IR-absorption at 1570 cm-'. 985 Scheme 1: Oxidation of diethyl4-phenylbutane-1, I -dicarboxylate (1)To find out the reason for the formation of the different products, the reaction was carried out in presence of various amounts of water and at different temp.. The distribution of products was analysed by the means of gas chromatography. In almost non-aqueous systems (less than 0.015% water, determined by Karl-Fischer titrations) the formation of mainly the nitro-and alcohol-derivatives was observed, only a small amount of the cyclic product 2 could be detected. The yield of 2 increased significantly upon increasing the water content. It should be stressed that even in the presence of 0.05% water, the amount of cyclization product surpassed the others. Beyond 3% water the relative amounts of the products remained constant (Fig. 1). Increasing temp. (between 20°C and 80"C, 0.3% of water) also influenced the distribution of...

Manganese(III)-Based Oxidative Free-Radical Cyclizations

“…Citterio and co-workers have comprehensively explored the use of ferric perchlorate in acetonitrile for oxidative intermolecular additions of malonate esters to styrenes and oxidative cyclizations of unsaturated malonate esters and compared this reagent to Mn(OAc) 3 and ceric ammonium nitrate. ,,,,− Co(OAc) 2 and molecular oxygen in acetic acid have been used for the oxidative addition of β-diketones and β-keto esters to alkenes. The oxidant is probably Co(III), and the addition product is trapped with oxygen, leading to a dihydrofuran analogous to that formed in eq 4. − Baciocchi and co-workers have used ceric ammonium nitrate to oxidize malonate esters to radicals in alcohol solvents. , The utility of ceric ammonium nitrate for oxidative cyclization of malonate esters and β-keto esters to aromatic systems has been examined by Citterio and co-workers. − ,, …”

“…Indan 195 is formed in modest yield ,, Oxidative cyclization of 5-aryl-3-oxopentanoates 196 with ceric ammonium nitrate in methanol leads to 2-hydroxy-1-naphthoate esters 199 in 30−60% yield …”

“…119,143 The utility of ceric ammonium nitrate for oxidative cyclization of malonate esters and β-keto esters to aromatic systems has been examined by Citterio and coworkers. [62][63][64]67,95 All of these oxidants are capable of forming radicals from 1,3-dicarbonyl compounds. However, the oxidant is also necessary for termination of the radical reaction.…”

“…60 These cyclizations can also be carried out with ceric ammonium nitrate and ferric perchlorate. 58,67,95 Oxidative cyclization of 5-aryl-3-oxopentanoates 196 with ceric ammonium nitrate in methanol leads to 2-hydroxy-1-naphthoate esters 199 in 30-60% yield. 62 Mn(OAc) 3 in acetic acid is usually less effective for these cyclizations.…”