Iron-catalyzed reactions acylation

Scheme 4-242. Synthesis of ketones by iron-catalyzed reaction of acyl chlorides with Grignard reagents.

Iron-catalyzed cross-coupling reactions of various acyl chlorides or thioesters with Grignard reagents have been pioneered by Marchese et al. and other research groups.322 These transformations provide general and convenient access to a wide range of ketones and have been further extended to the use of a supported iron(lll) complex.323... 

The first iron-catalyzed acylation of Grignard reagents was described by Kharasch and coworkers in 1944 (Scheme 6). They reported only one example of reaction between methyknagnesium iodide and mesitoyl chloride in the presence of iron(III) chloride in diethyl ether. 

Table 5.11 Range of acyl chlorides and sulfonates in iron-catalyzed cross-coupling reactions.

In analogy with iron-catalyzed Barbier-type reactions with Sml2 (cf. Scheme 8.5), intramolecular nucleophilic acyl substitutions (SNt) can be used to prepare cyclic ketones from esters [50]. An illustrative example is shown in Scheme 8.13 [51], Again, tris(l,3-diphenyl-l,3-propanedionato)iron(III) [Fe(dbm)3] is used as the catalyst. Compound 40 is obtained as one racemic diastereoisomer. 

The iron-catalyzed [3 + 2]-cycloaddition (Huisgen reaction) of nitriles and carbonyl compounds as reported by Itoh et al. is one of the rare examples reported where an iron reagent can be utilized for the synthesis of 1,2,4-oxadiazoles (Scheme 9.35) [93]. In this reaction, methyl ketones are nitrated at the a-position by Fe(N03)3 to generate an a-nitro ketone. This intermediate rearranges to an acyl cyanate, which reacts further with the nitrile to give the heterocyclic product 48 in good to excellent yields (R1 = Ph, R2 = CH3 95% yield). 

Pd-catalyzed reactions, 9, 431 with pentaarylantimonys, 9, 430 with tetraorganylantimony(V) compounds, 9, 429 in C-heteroatom bond formations, 9, 432 in Friedel-Crafts acylation, 9, 433 Antimony donor ligands in iron carbonyls, 6, 57... 

Cobalt-, Manganese- and Iron-catalyzed Cross-coupling Reactions 9.4.2.1 Carbonylations and acylations... 

As to the mechanistic pathway of aerobic oxidations of this type Httle evidence of any details has emerged as yet [ 18]. However, it seems quite reasonable to assume the intermediacy of peracids being formed by autoxidation of the aldehydes [ 19,20]. Metals can be involved in various stages of oxidation processes like the described nickel(II)- or iron(III)-catalyzed reactions [21] acyl radicals may be produced by metals from aldehydes which then participate in the autoxidation of the aldehydes. Metals can direct the oxygen insertion itself, too, or promote other catalytic pathways as well as even inhibit catalytic turnover. 

Alternatively to Grignard reagents, diorganozinc compounds can also be introduced in iron-catalyzed coupling reactions with acyl chlorides to provide a wide range of polyfunctional ketones under mild reaction conditions. ... 

This impressive reaction is catalyzed by stearoyl-CoA desaturase, a 53-kD enzyme containing a nonheme iron center. NADH and oxygen (Og) are required, as are two other proteins cytochrome 65 reductase (a 43-kD flavo-protein) and cytochrome 65 (16.7 kD). All three proteins are associated with the endoplasmic reticulum membrane. Cytochrome reductase transfers a pair of electrons from NADH through FAD to cytochrome (Figure 25.14). Oxidation of reduced cytochrome be, is coupled to reduction of nonheme Fe to Fe in the desaturase. The Fe accepts a pair of electrons (one at a time in a cycle) from cytochrome b and creates a cis double bond at the 9,10-posi-tion of the stearoyl-CoA substrate. Og is the terminal electron acceptor in this fatty acyl desaturation cycle. Note that two water molecules are made, which means that four electrons are transferred overall. Two of these come through the reaction sequence from NADH, and two come from the fatty acyl substrate that is being dehydrogenated. 

The ability of iron(III) chloride genuinely to catalyze Friedel-Crafts acylation reactions has also been recognized by Holderich and co-workers [97]. By immobilizing the ionic liquid [BMIM]Cl/FeCl3 on a solid support, Holderich was able to acetylate mesitylene, anisole, and m-xylene with acetyl chloride in excellent yield. The performance of the iron-based ionic liquid was then compared with that of the corresponding chlorostannate(II) and chloroaluminate(III) ionic liquids. The results are given in Scheme 5.1-67 and Table 5.1-5. As can be seen, the iron catalyst gave superior results to the aluminium- or tin-based catalysts. The reactions were also carried out in the gas phase at between 200 and 300 °C. The acetylation reac-... 

A few further general examples of zinc catalytic activity or reactivity include the following. Other zinc-containing systems include a zinc phenoxide/nickel(0) catalytic system that can be used to carry out the chemo- and regioselective cyclotrimerization of monoynes.934 Zinc homoenolates have been used as novel nucleophiles in acylation and addition reactions and shown to have general utility.935,936 Iron/zinc species have been used in the oxidation of hydrocarbons, and the selectivity and conditions examined.362 There are implications for the mechanism of metal-catalyzed iodosylbenzene reactions with olefins from the observation that zinc triflate and a dizinc complex catalyze these reactions.937... 

There are several fatty acyl-CoA desaturases. Stearoyl-CoA desaturase [EC 1.14.99.5] (also referred to as acyl-CoA desaturase, fatty acid desaturase, and A -desaturase) catalyzes the reaction of stearoyl-CoA with dioxygen and a hydrogen donor (AH2) to produce oleoyl-CoA, two water molecules, and A. The enzyme requires iron as a cofactor. Linoleoyl-CoA desaturase [EC 1.14.99.25], also referred to as A -desaturase, cata-... 

Shi and coworkers found that vinyl acetates 68 are viable acceptors in addition reactions of alkylarenes 67 catalyzed by 10 mol% FeCl2 in the presence of di-tert-butyl peroxide (Fig. 15) [124]. (S-Branched ketones 69 were isolated in 13-94% yield. The reaction proceeded with best yields when the vinyl acetate 68 was more electron deficient, but both donor- and acceptor-substituted 1-arylvinyl acetates underwent the addition reaction. These reactivity patterns and the observation of dibenzyls as side products support a radical mechanism, which starts with a Fenton process as described in Fig. 14. Hydrogen abstraction from 67 forms a benzylic radical, which stabilizes by addition to 68. SET oxidation of the resulting electron-rich a-acyloxy radical by the oxidized iron species leads to reduced iron catalyst and a carbocation, which stabilizes to 69 by acyl transfer to ferf-butanol. However, a second SET oxidation of the benzylic radical to a benzylic cation prior to addition followed by a polar addition to 68 cannot be excluded completely for the most electron-rich substrates. 

Iron catalysts are very effective for the substitution of acyl chlorides [Eq. (198) 439.440] and thiol esters [Eq. (199) 376] with Grignard reagents to yield ketones. 1.4-Addition of Grignard reagents to an alkylidenemalonate derivative, as shown in Eq. (158) [182,183] was also promoted with an iron catalyst, but the degree of the asymmetric induction was inferior to that of the reaction catalyzed by nickel. 

Amidocarbonylation is a recently developed, organometallic-catalyzed route to amino acid generation - particularly A(-acyl a-amino acids - using either aldehydes or alkenes as starting materials and synthesis gas as an integral building block. The two principal classes of reaction are illustrated in eqs. (1) and (2). Both syntheses offer the opportunity to introduce two functionalities, amido and carboxylate, simultaneously where an amide is the co-reactant. Homogeneous amidocarbonylation catalysts are typically cobalt carbonyl-based, or utilize transition-metal binary systems, e. g. cobalt-rhodium, cobalt-palladium, and cobalt-iron. 

This reaction is catalyzed by a complex of three membrane-bound proteins NADH-cytochrome bs reductase, cytochrome b, and a desaturase (Figure 22.32). First, electrons are transferred from NADH to the FAD moiety of NADH-cytochrome b reductase. The heme iron atom of cytochrome h-, is then reduced to the Fe state. The nonheme iron atom of the desaturase is subsequently converted into the Fe state, which enables it to interact with and the saturated fatty acyl CoA substrate. A double bond is... 

The present methods for the preparation of N acyl a arylenamides include (i) reductive acylation of ketoximes with iron metal [2] or phosphines [3] in the presence of acyl chlorides or acyl anhydrides (Method A) (ii) metal catalyzed coupling of vinyl halides [4], triflates [5], or tosylates [6] with amides (Method B) (iii) reaction of imine intermediates derived from nitriles with acyl chlorides or anhydrides (Method C) [7] and(iv) Pd catalyzed coupling ofaryl tosylates with N acyl vinylamines (MethodD) [8]. 

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