Oxidation enolates, iron

Iron(III) chloride, enol acetate oxidation, 792 Iron(III) compounds... 

The a-alkoxy-substituted iron-acyl complex 8 is prepared by oxidation of the enolate prepared from iron-acetyl complex 6 and subsequent etherification12. 

The oxidation of /(-amino-substituted iron acyl complexes which are prepared via condensation reactions of iron-acyl enolates and imines or iminium ions26,5 -47-54 generates /(-lactams 32,33,61. Brief treatment with bromine in dichloromethane at low temperature is the usual procedure. 

In a significant addition to the synthesis of 1,2,4-oxadiazoles (Scheme 41), Itoh et al. discovered that the treatment of nitriles with iron(lll) nitrate in the presence of acetone or acetophenone gives the 3-acetyl- or 3-benzoyl-l,2,4-oxadiazoles 260, proposing that enolization and nitration gives an a-nitroketone, which then undergoes an acid-catalyzed dehydration to give the nitrile oxides 259 <2005S1935>. 

The first step of the reaction path involves the addition of H2O2 to the Fe " resting state to form an iron-oxo derivative known as Compound I, which is formally two oxidation equivalents above the Fe state (Fig. 2). The well studied Compound I contains a Fe" = 0 structure and a n cation radical. In the second step. Compound I is reduced to Compound II with a Fe =0 structure. The reduction of the n cation radical by a phenol or enol is accompanied by an electron transfer to Compound I and a proton transfer to a distal basic group (B), probably His 42 (Fig. 3, step 1). The native state is regenerated on one-electron reduction of Compound II by a phenol or an enol. In this process, electron and proton transfers occur to the ferryl group with simultaneous reduction of Fe" to Fe (Fig. 3, steps 2-3) and formation of water as the leaving group (Fig. 3, step 4). 

Sterically hindered, mesityl-substituted, stable enols 72 have been examined with regard to one-electron oxidation. Using two equivalents of a one-electron oxidant such as triarylaminium salts, iron(III)phenanthroline, thianthrenium perchlorate or ceric ammonium nitrate in acetonitrile-benzofurans 73 are obtained in good yields within a few seconds [111]. 

As revealed, cation radicals of ferrocenyl ethylenes do not undergo the cis-to-trans isomerization. Calculations show that the cation radical s center is located exclusively at the iron atom, with no participation of the ethylene bond (Todres et al. 1992). Hence, one-electron oxidation of this ferrocenyl ethylene occurs at the iron atom exclusively anything else would be extremely unusual in this case. Thus, the recently described stable enol linked to a ferrocene redox center gives the cation radical upon one-electron oxidation. This species is better characterized as a ferricenium salt than as an enol cation radical (Schmit-tel Langels 1998). 

The mechanism of the catalytic cycle is outlined in Scheme 1.37 [11]. It involves the formation of a reactive 16-electron tricarbonyliron species by coordination of allyl alcohol to pentacarbonyliron and sequential loss of two carbon monoxide ligands. Oxidative addition to a Jt-allyl hydride complex with iron in the oxidation state +2, followed by reductive elimination, affords an alkene-tricarbonyliron complex. As a result of the [1, 3]-hydride shift the allyl alcohol has been converted to an enol, which is released and the catalytically active tricarbonyliron species is regenerated. This example demonstrates that oxidation and reduction steps can be merged to a one-pot procedure by transferring them into oxidative addition and reductive elimination using the transition metal as a reversible switch. Recently, this reaction has been integrated into a tandem isomerization-aldolization reaction which was applied to the synthesis of indanones and indenones [81] and for the transformation of vinylic furanoses into cydopentenones [82]. 

Li and coworkers published addition reactions of ethers, sulfides, or tertiary amines 40 to p-dicarbonyl compounds 39 (Fig. 8) [96]. Fe2(CO)9 proved to be the catalyst of choice and di-tert-butyl peroxide the optimal oxidant. a-Functionalized p-dicarbonyl compounds 41 were isolated in 52-98% yield. Although the details of the catalytic cycle remain unclear, it seems to be likely that the peroxide is reductively cleaved by the Fe(0) catalyst leading to an Fe(I) complex and a ferf-butoxyl radical, which abstracts the a-hydrogen atom of 40. Addition of the resulting radical to the free enol form of 39 or the corresponding iron enolate of 39 may subsequently occur. It remains unclear, however, whether the main catalytic reaction proceeds on an Fe(0)-Fe(I) oxidation stage or whether further oxidation of initially formed Fe(I) rather leads to an Fe(II) catalyst. This cannot be excluded,... 

When the enols 1,3,5-10 were reacted with 2 equivalents of weU known one-electron oxidants, e.g. triarylaminium salts, iron(III)phenanthroline (FePHEN)... 

Hence, the first clearcut evidence for the involvement of enol radical cations in ketone oxidation reactions was provided by Henry [109] and Littler [110,112]. From kinetic results and product studies it was concluded that in the oxidation of cyclohexanone using the outer-sphere one-electron oxidants, tris-substituted 2,2 -bipyridyl or 1,10-phenanthroline complexes of iron(III) and ruthenium(III) or sodium hexachloroiridate(IV) (IrCI), the cyclohexenol radical cation (65" ) is formed, which rapidly deprotonates to the a-carbonyl radical 66. An upper limit for the deuterium isotope effect in the oxidation step (k /kjy < 2) suggests that electron transfer from the enol to the metal complex occurs prior to the loss of the proton [109]. In the reaction with the ruthenium(III) salt, four main products were formed 2-hydroxycyclohexanone (67), cyclohexenone, cyclopen tanecarboxylic acid and 1,2-cyclohexanedione, whereas oxidation with IrCl afforded 2-chlorocyclohexanone in almost quantitative yield. Similarly, enol radical cations can be invoked in the oxidation reactions of aliphatic ketones with the substitution inert dodecatungstocobaltate(III), CoW,20 o complex [169]. Unfortunately, these results have never been linked to the general concept of inversion of stability order of enol/ketone systems (Sect. 2) and thus have never received wide attention. 

In a series of papers on the total syntheses of alkaloids, Baran and coworkers have recently reported that enolates of carbonyl compounds undergo oxidative coupling with indoles and pyrroles in the presence of oxidants such as copper(II) and iron(III) salts . A detailed study of the oxidative cyclization reported in equation 15 has shown that 26 is converted into 27 with the highest yields when Fe(acac)3 is the oxidant, presumably due to its high redox potential (+1.1 V vs. the ferrocenium/ferrocene couple in THF solution ), which is the most positive among all the oxidizing agents tested for the transformation. 

Chiral enolates in which the auxiliary is in the ester portion provide still another route to optically active lactams. Early results indicated that little asymmetric induction was obtained with menthyl enolates. Use of the enolate obtained from 24 did lead to high levels of asymmetric induction. Treatment of 24 with lithium diisopropylamide in tetrahydrofuran, followed by addition of imine 25, gives cf -/(-lactam 26 in 79% yield and 91%ee98. Optically active /3-lactams can be prepared by addition of chiral iron enolates (see Section D.l. 1.1.3.2.) to imines99-101. Addition of aluminum enolate 27 to imine 28, followed by oxidative cyclization with iodine and an amine, affords /(-lactam 29 in 54% yield and >95% ee. 

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