Iron enolates acetyl

Iron-acyl enolates such as 1, 2, and 3 react readily with electrophiles such as alkyl halides and carbonyl compounds (see Houben-Weyl, Vol. 13/9a p418). The reactions of these enolatc species with alkyl halides and similar electrophiles are discussed in Section D.1.1.1.3.4.1.3. To date, only the simple enolates prepared by a-deprotonation of acetyl and propanoyl complexes have been reacted with ketones or aldehydes. 

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

I.3.4.2.5.I.2. Aldol Additions of Enolates of Chiral Iron-Acetyl Complexes... 

No efforts to improve the diastcreoselectivity of the reaction of iron acetyl enolates with unsymmetrical ketones have been reported. 

The aldol reaction of iron-acetyl enolates such as 1 with aldehydes creates a new stereogenic center at the (S-carbon of the product complexes. 

A powerful variation of the iron acetyl enolate aldol reaction utilizes the cnolate of complex 8 which bears a (pentafluorophenyl)diphenylphosphane ligand in place of the more usual triphenylphosphane47. The enolate species 9. prepared by treatment of 8 with lithium diiso-propylamide, reacts at — 78 °C with benzaldehyde to produce the aldol adduct 10 with a d.r. of 98.5 1.5. 

Aldol reactions of a-substituted iron-acetyl enolates such as 1 generate a stcrcogenic center at the a-carbon, which engenders the possibility of two diastereomeric aldol adducts 2 and 3 on reaction with symmetrical ketones, and the possibility of four diastereomeric aldol adducts 4, 5, 6, and 7 on reaction with aldehydes or unsymmetrical ketones. The following sections describe the asymmetric aldol reactions of chiral enolate species such as 1. 

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>. 

Presumed (based on subsequent reactions) major diastereomer. b Optically pure prepared from optically pure (S)-acetyl (dicarbonyl)(triphenylphosphane)iron by reaction known not to affect the slereogenic iron functionality. c Enolate warmed to — 42 °C,... 

One of the simplest biochemical addition reactions is the hydration of carbon dioxide to form carbonic acid, which is released from the zinc-containing carbonic anhydrase (left, Fig. 13-1) as HC03-. Aconitase (center, Fig. 13-4) is shown here removing a water molecule from isocitrate, an intermediate compound in the citric acid cycle. The H20 that is removed will become bonded to an iron atom of the Fe4S4 cluster at the active site as indicated by the black H20. An enolate anion derived from acetyl-CoA adds to the carbonyl group of oxaloacetate to form citrate in the active site of citrate synthase (right, Fig. 13-9) to initiate the citric acid cycle. 

An interesting metal effect was observed in the aldol condensations of the enolate derived from the iron acetyl complex (r)"-C HdFe(CO)(PPhd(COMe) with aldehydes [56,57]. Although the lithium enolate did not show any selectivity, the corresponding aluminum enolate by transmetalation with Et.AlCl exhibited exceptionally high diastereoselectivity (>99% de). The resultant P-hydroxy acyl complexes are transformed to P-hydroxy acids on decomplexation with Br.. 

In the presence of Et2AlCl the lithium enolate derived from the iron acetyl complex [(C H )Fe(CO)(PPh )C0Me] discriminates between... 

Chiral acetyl iron complexes 76 also seem predestined to serve as reagents that enable introduction of a chiral acetate unit into aldehydes. In contrast with the benzyloxy-substituted derivative 66b (Eq. (30)), however, only marginal induced stereoselectivity is achieved when the lithium enolate of 76 is added to aldehydes, and the diastereomer 77a is formed in low preference compared with 77b (Eq. (33)). High diastereoselectivity is obtained only after transmetalation [112, 114, 115]. 

A significant improvement - as far as chiral lithium enolates of acetyl iron complexes are concerned - came from the complex 78, which carries a (pentafiuorophenyl)diphenylphosphane ligand instead of the usual tri-phenylphosphane. Thus, the enolate 79, generated by treatment with LDA, gives the diastereomeric adducts 80a and 80b in a diastereomeric ratio of 98.5 1.5 on treatment with benzaldehyde. A donor-acceptor interaction between the enolate oxygen atom and the fiuorinated aromatic ring, supported... 

Another early solution to the acetate aldol problem came from the so-called Davies-Liebeskind enolates already mentioned in the context of enolate alkylation. As elaborated independently by the groups of Davies [138] and Liebeskind [139], the deprotonation of the chiral acetyl iron complex 124b, transmetallation of the lithium enolate, and addition to aldehydes lead to the predominant formation of diastereomers 279, as proved by a crystal structure analysis. The diastereoselectivity strongly depends on the transmetallation, the best results being obtained with diethylaluminum chloride. With other additives, the topicity is reversed, and the diastereomer 280 is obtained as the major product. The decomplexation of the adducts leads to P-hydroxycarboxylic acids (Scheme 4.64). 

Scheme 4.64 Acetate aldol addition with Iron acetyl complex 124b via Davies-Liebeskind enolates.

The procedure was also extended to the analogous propionyl and benzy-loxyacetyl iron complexes. Although the preparation of enantiomeric iron acetyl complexes (R)- and (S )-124b is Icnown and the reagent became even commercially available under both enantiomeric forms, it was nevertheless used as racemate. It seems that the immolative character of the aldol additions based on Davies-Liebeskind enolates prevented wider application in larger scale [140]. 

Of special interest are chiral-at-iron complexes bearing a carbonyl, a phosphane, a Cp, and an acetyl ligand. The racemic complexes can be kinetically resolved by aldol reaction of their enolates with (l/ )-(+)-camphor (Scheme 4-43). " ... 

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