Arene oxides nucleophilic addition reaction

In general, nucleophilic addition reactions of arene oxides with nonpolarizable oxygen and nitrogen nucleophiles are very slow. Thus both NH3 and NHj nucleophiles failed to add to benzene oxides under a range of conditions. Amine nucleophiles have, however, been found to react very slowly with benzene oxide. 

Fig. 2. Reactions of arene oxides. Spontaneous aromatization into phenols and nucleophilic addition reactions by amines and thiols...

The overall reaction catalyzed by epoxide hydrolases is the addition of a H20 molecule to an epoxide. Alkene oxides, thus, yield diols (Fig. 10.5), whereas arene oxides yield dihydrodiols (cf. Fig. 10.8). In earlier studies, it had been postulated that epoxide hydrolases act by enhancing the nucleo-philicity of a H20 molecule and directing it to attack an epoxide, as pictured in Fig. 10.5, a [59] [60], Further evidence such as the lack of incorporation of 180 from H2180 into the substrate, the isolation of an ester intermediate, and the effects of group-selective reagents and carefully designed inhibitors led to a more-elaborate model [59][61 - 67]. As pictured in Fig. 10.5,b, nucleophilic attack of the substrate is mediated by a carboxylate group in the catalytic site to form an ester intermediate. In a second step, an activated H20... 

The K-region oxides undergo nucleophilic addition with OH", C032", water, amines, and mercaptides.88,140 The second-order rate constants for the reactions of OH", water, and primary and secondary amines with 1 at 30°C and with ethylene oxide at 25°C141 can be simply related by Eq. (6),2 which shows that the sensitivity of the two oxides to the nature of the nucleophile is similar and that the arene oxide is more reactive. 

The reaction is highly regio- and stereospecihc, always proceeding with inversion of configuration. With arene oxides, this means that only tranx-dihydrodiols are formed. All of the experimental evidence points to a general base-catalyzed nucleophilic (S,v2) addition of water to the oxirane ring. 

Arene oxides show the characteristic reactions of epoxides (isomerization to ketones, reductions to alcohols, nucleophilic additions, deoxygenations) and olefins or conjugated dienes (catalytic hydrogenation, photochemical isomerization, cycloaddition, epoxidation, metal complexation). Where a spontaneous, rapid equilibration between the arene oxide and oxepin forms exists, reactivity typical of a conjugated triene is also found. 

The reactions of strong carbon nucleophiles with arene oxides 1 and 11 leads to rapid adduct formation.Methyl lithium and dimethyl magnesium react with arene oxide 1 by 1,6-addition to give ds-adducts. Trans-adducts were also obtained from reaction of dimethyl magnesium and methyl lithium with arene oxides 1 and 11, respectively, by the more usual 1,2-trans addition mechanism. ... 

Is usually mixed with the arene oxide In a polar solvent such as acetone, dioxane, acetonitrile, DMSO or methanol but the reaction may also be run In aqueous buffer solutions. Even though the addition of base Increases the nucleophilicity of the sulfur, the pH should not be Increased too much since that will lead to more complex reaction product mixtures (167). A PTC mediated reaction with tetrabutylammonlum blsulfate has been suggested for the synthesis of N-acetyl-cystelne conjugates of epoxides (167). The recent synthesis of some premercapturlc acid type conjugates from epoxides Is summerlzed In Table VII. 

One of the first eye-catching synthetic applications of arene-chromium chemistry was the synthesis of the sp/ro-sesquiterpenes ( )-acorenone and ( )-acorenone B (rac-7) disclosed by Semmelhack and Yamashita in 1980 [14]. These authors twice exploited the meta-selective nucleophile addition to anisole-Cr(CO)3 derivatives (Scheme 1). Starting from complex rac-1, such a reaction is first used for the regioselective introduction of an acyl sidechain to give 2 after oxidative workup. A few steps later, the nitrile rac-4 (obtained from rac-3 by complexation and separation of the diastereomeric products by preparative HPLC) is deprotonated to form the spiro addition product rac-5, from which the enone rac-6 is obtained after protonation and hydrolysis of the initially formed dienol ether. The final conversion of rac-6 into acorenone B (rac-7) efficiently proceeds over five steps and involves a diastereoselective hydrogenation of an exo-methylene group. 

---