Chiral iron acyls

I.3.4.2.5. Chiral Enolates of Acyl-Metal Complexes J. S. McCallum and L. S. Liebeskind I.3.4.2.5.I. Chiral Iron-Acyl Complexes... 

Alkylation of the anion 2 with iodomethane or other haloalkanes provides alkyldicarbonyl(t/5-cyclopentadienyl)iron complexes such as 53,0 (see also Houben-Weyl, Vol. 13/9a, p 209). Migratory insertion of carbon monoxide occurs on treatment with phosphanes or phosphites9 -11 (see also Houben-Weyl, Vol. d3/9a, p257) to provide chiral iron-acyl complexes such as 6. This is the most commonly used preparation of racemic chiral iron-acyl complexes. 

Enantiomerically Pure Chiral Iron-Acyl Complexes... 

The reported preparations of enantiomerically pure chiral iron-acyl complexes have relied upon resolutions of diastereomers. One route1415 (see also Houben-Weyl, Vol. 13/9 a, p 421) employs a resolution of the diastereomeric acylmenlhyloxy complexes (Fe/ )-3 and (FeS )-3 prepared via nucleophilic attack of the chiral menlhyloxide ion of 2 at a carbon monoxide of the iron cation of 1. Subsequent nucleophilic displacement of menthyloxide occurs with inversion at iron to generate the enantiomerically pure iron-acyl complexes (i>)-4 and (f )-4. 

Subsequent carbonylation of the alkyl-iron complexes with carbon monoxide provides the desired chiral iron-acyl complexes, with essentially complete inversion of configuration at... 

Alkylation of Enolates of Chiral Iron-Acyl Enolates by Electrophiles... 

Table 6. Alkylation of a-Enolates 2 of Chiral Iron-Acyl Complexes 1 by Carbon Electrophiles...

Chiral iron acyl complexes have been applied to the asymmetric synthesis of cyclopropane carboxylic acids, sulfoxides and p-amino acids. Further details and applications may be found in the reviews given in the reference... 

The deprotonation of chiral iron acyl complexes, which can be obtained as enantiomerically pure compounds, leads to the corresponding enolates, as shown by the research groups of Davies and Liebeskind [112-115]. The lithium enolate 67a, however, which originates from propanoate 66a, reacts stereoselectively with aldehydes or ketones only if it has been transmetalated into the corresponding copper or aluminum enolate (Eq. (30)) [116]. 

The dicarbonyl species thus produced undergo photolytically promoted carbon monoxide displacement by phosphine to give racemic mixtures of chiral a,/ -unsaturated iron-acyl complexes35. 

Table 5. Carboxylic Acids 5 by Removal of the Chiral Auxiliary from Iron-Acyl Complexes 4...

Addition of organolithium compounds to chiral ( )-configured a, -unsaturated iron acyl complexes (116) proceeds with an exceptionally high degree of asymmetric induction.127-132 The initially formed... 

Review. Davies has reviewed use of the chiral iron auxiliary [CpFe-(CO)P(C6H5)3] for effecting asymmetric reactions of an acyl group, including alkylation, aldol reactions, Michael additions. 

Iron acyl complexes are among the most widely studied of the organometallic iron species, especially as applied to organic synthesis. As previonsly mentioned they are prepared to provide access to iron alkyls (via decarbonylation), and because iron acyls can be deprotonated to form enolates much like any carbonyl they have been utilized as chiral auxiliaries in asymmetric synthesis. Also, iron acyls are an important entry point for the preparation of iron carbenes. 

To prepare the enantiomerically pure iron acyl complex (R)-(39), a precursor diastereomeric menthoxyaUcyl complex was resolved and then manipulated (Scheme 14). More recently resolution of the chiral-at-metal acyl complexes themselves was achieved, and this has become the basis for a commercial preparation of the iron acyl developed for use as a chiral auxiliary (see below). Cationic iron complex (43) was treated with potassium L-mentholate to produce diastereomeric esters (44) that were not isolated but were reacted with LiBr/MeLi (Scheme 15). After chromatography and recrystallization the enantiomerically pure ironacyl complex (5 )-(39a) was obtained. It was suggested that only one diastereomeric ester can react (with inversion of configuration at iron, as shown) with the methyl nucleophile the unreactive diastereomer suffers from severe steric congestion about the electrophilic CO ligand. 

Cyclopropanation reactions of nonheteroatom-stabilized carbenes have also been developed. The most versatile are the cationic iron carbenes that cyclopropanate alkenes with high stereospecificity under very mild reaction conditions. The cyclopropanation reagents are available from a number of iron complexes, for example, (9-alkylation of cyclopentadienyl dicarbonyliron alkyl or acyl complexes using Meerwein salts affords cationic Fischer carbenes. Cationic iron carbene intermediates can also be prepared by reaction of CpFe(CO)2 with aldehydes followed by treatment with TMS-chloride. Chiral intermolecular cyclopropanation using a chiral iron carbene having a complexed chromium tricarbonyl unit is observed (Scheme 61). 

Conjugate addition reactions of N-nucleophiles with double stereodifferentiation are known in some cases11-116. While direct reaction of chiral amines with chiral enones11 leads to poor enantiomeric excess of the resulting /l-amino acids, reaction of chiral amines116 with acylated chiral iron complexes gives /J-amino acids with a high enantiomeric excess. 

Enolates of iron-acyl complexes have been studied extensively, especially by Davies and Liebeskind and their respective coworkers. The chiral complex [T) -CpFe(PPh3)(CO)COCH2R] is usually used it can be prepared in racemic or optically active form. The enolate usually has the anti conformation with regard to CO and Copper (Z)-enolates give predominantly syn aldols, whereas diethylalumin-... 

Davies and Liebeskind independently prepared chiral aluminum enolates from enantiomerically homogeneous acyl-iron complexes (137) and recorded the first aluminum-mediated asymmetric aldol reactions. Although the lithium enolate of the chiral iron complex (CHIRAC) provides aldol products with... 

A very different, but similarly effective, auxiliary is the chiral carbonyl(t/5-cyclopentadienyl)(tri-phenylphosphine)iron moiety. When the z./i-unsaturated acyl-iron complex ( -)-(/ )-11 is treated by a modified Simmons Smith reagent, a 91 9 mixture of cyclopropane diastereomers is isolated in good yield73. Precomplexation of the starting iron complex by the Lewis acid zinc(II) chloride seems to be necessary to obtain good selectivity. The chiral iron moiety can then be removed oxidatively by bromine treatment, and the intermediate acyl bromides converted into amides by reaction with (/ )- -phenylethylamine. 

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